References
_________________________________________________________________________
Achan, J., Talisuna, A. O., Erhart, A., Yeka, A., Tibenderana, J. K., Baliraine, F. N., Rosenthal, P. J. & D‟Alessandro, U. 2011. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malaria Journal, 11: 144-155.
Aly, A. S. I. & Matuschewski, K. 2005. A malarial cysteine protease is necessary for
Plasmodium sporozoite egress from oocysts. The Journal of Experimental Medicine,
202: 225-230.
Andre, F., Booy, R., Bock, H., Clemens, J., Datta, S., John, T., Lee, B., Lolekha, S., Peltola, H., Ruff, T., Santosham, M. & Schmitt, H. 2008. Vaccination greatly reduces disease, disability, death and inequity worldwide. Bulletin of the World Health
Organization 86: 140-146.
ANON. 1979. Antimalaria studies on Qinghaosu. Chinese Medical Journal, 92: 811-816. ANON. 2010. Malaria. Malaria Health Centre, [WEB]:
http://healthcenterdiseaseinformationes.webs.com/malaria.htm. (Date of Access: November 2013).
ANON. 2012. One step closer to blocking the transmission of malaria. Medicines for
Malaria Venture (MMV), [WEB]:
http://www.mmv.org/newsroom/press-releases/one-step-closer-blocking-transmission-malaria. [Date of access: October 2013].
ANON. Nobel Media. 2013. Alphonse Laveran: biographical. Nobelprize.org. [WEB]: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1907/laveran-bio.html. [Date of access: October 2013].
Ashley, E., McGready, R., Proux, S. & Nosten, F. 2006. Malaria. Travel Medicine and
Infectious Disease, 4: 159-173.
Attar, S., O'Brien, Z., Alhaddad, H., Golden, M. L. & Calderón-Urrea, A. 2011. Ferrocenyl chalcones versus organic chalcones: a comparative study of their nematocidal activity. Bioorganic & Medicinal Chemistry, 19: 2055-2073.
Barsoum, R. S. 2000. Malarial acute renal failure. Journal of the American Society of
Nephrology, 11: 2147-2154.
Baumeister, S., Endermann, T., Charpian, S., Nyalwidhe, J., Duranton, C., Huber, S., Kirk, K., Lang, F. & Lingelbach, K. 2003. A biotin derivative blocks parasite induced novel permeation pathways in Plasmodium falciparum-infected erythrocytes. Molecular and
Biochemical Parasitology, 132: 35-45.
Beagley, P., Blackie, M. A. L., Chibale, K., Clarkson, C., Meijboom, R., Moss, J. R., Smith, P. J. & Su, H. 2003. Synthesis and antiplasmodial activity in vitro of new
ferrocene-chloroquine analogues. Journal of the Chemical Society, Dalton Transactions, 3046-3051.
Beare, N. A. V., Taylor, T. E., Harding, S. P., Lewallen, S. & Molyneux, M. E. 2006. Malarial retinopathy: a newly established diagnostic sign in severe malaria. American Society
of Tropical Medicine and Hygiene, 75: 790-797.
Bhattacharya, A., Mishra, L. C., Sharma, M., Awasthi, S. K. & Bhasin, V. K. 2009. Antimalarial pharmacodynamics of chalcone derivatives in combination with artemisinin against Plasmodium falciparum in vitro. European Journal of Medicinal
Chemistry, 44: 3388-3393.
Bilolikar, H. G., Bagade, A. C., Phadke, M. & Gambhir, P. S. 1994. Indian Pediatrics, 31: 595-599.
Bouchaud, O., Imbert, P., Touze, J., Dodoo, A., Danis, M. & Legros, F. 2009. Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base. Malaria Journal, 8: 289.
Bray, P. G. 2005. Quinolines and artemisinin: chemistry, biology and history. Current
Topics in Microbiology and Immunology, 295: 3-38.
Chibale, K., Moss, J. R., Blackie, M., van Schalkwyk, D. & Smith, P. J. 2000. New amine and urea analogs of ferrochloroquine: synthesis, antimalarial activity in vitro and electrochemical studies. Tetrahedron Letters, 41: 6231-6235.
Cloete, T. T., Krebs, H. J., Clark, J. A., Connelly, M. C., Orcutt, A., Sigal, M. S., Guy, R. K. & N‟Da, D. D. 2013. Antimalarial activity of 10-alkyl/aryl esters and -aminoethylethers of artemisinin. Bioorganic Chemistry, 46: 10-16.
Cui, L. & Su, X. Z. 2009. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Review of Anti-Infective Therapy, 8: 999-1013.
Cui, L., Wang, Z., Jiang, H., Parker, D., Wang, H., Su, X. Z. & Cui, L. 2012. Lack of association of the S769N mutation in Plasmodium falciparum SERCA (PfATP6) with resistance to artemisinins. Antimicrobial Agents and Chemotherapy, 56: 2546-2552. Das, B. S. 2008. Renal failure in malaria. Journal of Vector Borne Diseases, 45: 83-97. Doolan, D. L., Dobaño, C. & Baird, J. K. 2009. Acquired immunity to malaria. Clinical
Microbiology Review, 22: 13-36.
Egan, T. J. 2008. Haemozoin formation. Molecular and Biochemical Parasitology, 157: 127-136.
English, M., Sauerwein, R., Waruiru, C., Mosobo, M., Obiero, J., Lowe, B. & Marsh, K. 1997. Acidosis in severe childhood malaria. QJM, 90: 263-270.
Ettari, R., Bova, F., Zappalà, M., Grasso, S. & Micale, N. 2009. Falcipain-2 inhibitors.
Fernando, D., Rodrigo, C. & Rajapakse, S. 2011. Primaquine in vivax malaria: an update and review on management issues. Malaria Journal, 10: 351.
Foley, M. & Tilley, L. 1998. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacology & Therapeutics, 79: 55–87.
Franke-Fayard, B., Fonager, J., Braks, A., Khan, S. M. & Janse, C. J. 2010. Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria? PLoS Pathogens, 6: 1-10.
Fujioka, H. & Aikawa, M. 2002. Structure and life cycle. Perlmann P, Troye-Blomberg M
(eds): Malaria Immunology Chem Immunol. Basel, Karger, 80: 1-26.
Gibbons, P., Verissimo, E., Araujo, N. C., Barton, V., Nixon, G. L., Amewu, R. K., Chadwick, J., Stocks, P. A., Biagini, G. A., Srivastava, A., Rosenthal, P. J., Gut, J., Guedes, R. C., Moreira, R., Sharma, R., Berry, N., Cristiano, M. L. S., Shone, A. E., Ward, S. A. & O'Neill, P. M. 2010. Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: toward combination chemotherapy of malaria through a single chemical entity. Journal of
Medicinal Chemistry, 53: 8202-8206.
Gimeno, M. C., Goitia, H., Laguna, A., Luque, M. E., Villacampa, M. D., Sepúlveda, C. & Meireles, M. 2011. Conjugates of ferrocene with biological compounds: coordination to gold complexes and antitumoral properties. Journal of Inorganic Biochemistry, 105: 1373-1382.
Go, M. L., Liu, M., Wilairat, P., Rosenthal, P. J., Saliba, K. J. & Kirk, K. 2004. Antiplasmodial chalcones inhibit sorbitol-induced hemolysis of Plasmodium
falciparum-infected erythrocytes. Antimicrobial Agents and Chemotherapy, 48:
3241-3245.
Gregson, A. & Plowe, C. V. 2005. Mechanisms of resistance of malaria parasites to antifolates. Pharmacological Reviews, 57: 117-145.
Grewal, R. S. 1981. Pharmacology of 8-aminoquinolines. Bulletin of the World Health
Organization, 59: 397-406.
Gutman, J., Kachur, S. P., Slutsker, L., Nzila, A. & Mutabingwa, T. 2013. Combination of probenecid-sulphadoxinepyrimethamine for intermittent preventive treatment in pregnancy. Malaria Journal, 11: 39-48.
Gyan, B. A., Goka, B., Cvetkovic, J. T., Kurtzhalst, J. L., Adabayeri, V., Perlmannt, H., Lefvert, A. K., Akanmori, B. D. & Troye-Blomberg, M. 2004. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children. Clinical & Experimental Immunology, 138: 145-150.
Hans, R. H., Gut, J., Rosenthal, P. J. & Chibale, K. 2010. Comparison of the antiplasmodial and falcipain-2 inhibitory activity of ß-amino alcohol thiolactone-chalcone and isatin-chalcone hybrids. Bioorganic & Medicinal Chemistry Letters, 20: 2234-2237.
Haynes, R. K. & Krishna, S. 2004. Artemisinins: activities and actions. Microbes and
Infection, 6: 1339-1346.
Hobbs, C. & Duffy, P. 2011. Drugs for malaria: something old, something new, something borrowed. Biology Reports, 3: 24-32.
Hopkins, H. 2013. Diagnosis of malaria. [WEB]:
http://www.uptodate.com/contents/diagnosis-of-malaria#H6885923. [Date of Access: November 2013].
Hyde, J. E. 2005. Exploring the folate pathway in Plasmodium falciparum. Acta Tropica, 94: 191-206.
Idro, R., Marsh, K., John, C. C. & Newton, C. R. 2010. Cerebral malaria: mechanisms of brain injury and strategies for improved neuro-cognitive outcome. Pediatric
Research, 68: 267-274.
Jayasinghe, L., Balasooriya, B. A. I. S., Padmini, W. C., Hara, N. & Fujimoto, Y. 2004. Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis. Phytochemistry, 65: 1287-1290.
Jensen, M. & Mehlhorn, H. 2009. Seventy-five years of Resochin® in the fight against
malaria. Parasitology Research, 105: 609–627.
Kaur, K., Jain, M., Reddy, R. P. & Jain, R. 2010. Quinolines and structurally related heterocycles as antimalarials. European Journal of Medicinal Chemistry, 45: 3245-3264.
Kremsner, P. G., Radloff, P., Metzger, W., Wildling, E., Mordmüller, B., Philipps, J., Jenne, L., Nkeyi, M., Prada, J., Bienzle, U. & Graninger, W. 1995. Quinine plus clindamycin improves chemotherapy of severe malaria in children. Antimicrobial Agents and
Chemotherapy, 39: 1603-1605.
Krishna, S., Bustamante, L., Haynes, R. K. & Staines, H. M. 2008. Artemisinins: their growing importance in medicine. Trends in Pharmacological Sciences, 29: 520-527. Krugliak, M., Zhang, J. & Ginsburg, H. 2002. Intraerythrocytic Plasmodium falciparum
utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins. Molecular and Biochemical Parasitology, 119: 249-256.
Kumar, R., Mohanakrishnan, D., Sharma, A., Kaushik, N. K., Kalia, K., Sinha, A. K. & Sahal, D. 2010. Reinvestigation of structure-activity relationship of methoxylated chalcones as antimalarials: Synthesis and evaluation of 2,4,5-trimethoxy substituted patterns as
lead candidates derived from abundantly available natural β-asarone. European
Journal of Medicinal Chemistry, 45: 5292-5301.
Larsen, M., Kromann, H., Kharazmi, A. & Nielsen, S. F. 2005. Conformationally restricted anti-plasmodial chalcones. Bioorganic & Medicinal Chemistry Letters, 15: 4858-4861.
Li, J. & Zhou, B. 2010. Biological actions of artemisinin: insights from medicinal chemistry studies. Molecules, 15: 1378-1397.
Li, R., Kenyon, G. L., Cohen, F. E., Chen, X., Gong, B., Dominguez, J. N., Davidson, E., Kurzban, G., Miller, R. E., Nuzum, E. O., Rosenthal, P. J. & McKerrow, J. H. 1995.
In vitro antimalarial activity of chalcones and their derivatives. Journal of Medicinal Chemistry, 38: 5031-5037.
Liu, M., Wilairat, P., Croft, S. L., Tan, A. L. C. & Go, M. L. 2003. Structure-activity relationships of antileishmanial and antimalarial chalcones. Bioorganic & Medicinal
Chemistry, 11: 2729-2738.
Maitland, K. & Newton, C. R. J. C. 2005. Acidosis of severe falciparum malaria: heading for a shock? Trends in Parasitology, 21: 11-16.
Makani, J., Komba, A. N., Cox, S. E., Oruo, J., Mwamtemi, K., Kitundu, J., Magesa, P., Rwezaula, S., Meda, E., Mgaya, J., Pallangyo, K., Okiro, E., Muturi, D., Newton, C. R., Fegan, G., Marsh, K. & Williams, T. N. 2010. Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization. Blood, 115: 215-220.
Martin, R. E. & Kirk, K. 2004. The malaria parasite's chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily. Molecular Biology and
Evolution, 21: 1938-1949.
Mather, M. W., Darrouzet, E., Valkova-Valchanova, M., Cooley, J. W., McIntosh, M. T., Daldal, F. & Vaidya, A. B. 2005. Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. Journal of Biological
Chemistry, 280: 27458-27465.
Mathiyalagan, K., Gopal, S., Ramasamy, E. & Vennila, T. 2012. In-vitro antimicrobial screening of ferrocene derived compounds. International Journal of ChemTech
Research, 4: 1775-1781.
Meunier, B. 2008. Hybrid molecules with a dual mode of action: dream or reality? Accounts
of Chemical Research, 41: 69-77.
Miller, L. H., Mason, S. J., Clyde, D. F. & McGinniss, M. H. 1976. The resistance factor to
Plasmodium vivax in Blacks. New England Journal of Medicine, 295: 302-304.
Moody, A. H. & Chiodini, P. L. 2000. Methods for the detection of blood parasites. Clinical &
Laboratory Haematology, 22: 189-201.
MRC. 2008. Evaluation Of malaria health education interventions using knowledge,
attitudes and practices (KAP) In South Africa [WEB]:
http://www.mrc.ac.za/malaria/SAKAP.pdf. (Date of Access: November 2013).
Mubi, M., Kakoko, D., Ngasala, B., Premji, Z., Peterson, S., Bjorkman, A. & Martensson, A. 2013. Malaria diagnosis and treatment practices following introduction of rapid
diagnostic tests in Kibaha District, Coast Region, Tanzania. Malaria Journal, 12: 293-300.
Muller, T. J., Conradie, J. & Erasmus, E. 2012. A spectroscopic, electrochemical and DFT study of para-substituted ferrocene-containing chalcone derivatives: structure of
FcCOCHCH(p-tBuC6H4). Polyhedron, 33: 257-266.
N'Da, D. D., Breytenbach, J. C., Smith, P. J. & Lategan, C. 2010. Synthesis, cytotoxicity
and antimalarial activity of ferrocenyl amides of 4-aminoquinolines.
Arzneimittelforschung, 60: 627-635.
Nabi, G. & Liu, Z. Q. 2011. Radical-scavenging properties of ferrocenyl chalcones.
Bioorganic & Medicinal Chemistry Letters, 21: 944-946.
Nakato, H., Vivancos, R. & Hunter, P. R. 2007. A systematic review and meta-analysis of
the effectiveness and safety of atovaquone-proguanil (Malarone) for
chemoprophylaxis against malaria. Journal of Antimicrobial Chemotherapy, 60: 929-936.
Navarro-Martínez, M. D., Navarro-Perán, E., Cabezas-Herrera, J., Ruiz-Gómez, J., García-Cánovas, F. & Rodríguez-López, J. N. 2005. Antifolate activity of epigallocatechin
gallate against stenotrophomonas maltophilia. Antimicrobial Agents and
Chemotherapy, 49: 2914-2920.
Neote, K., Mak, J. Y., Kolakowski, L. F. & Schall, T. J. 1994. Functional and biochemical analysis of the cloned Duffy antigen: identity with the red blood cell chemokine receptor. Blood, 84: 44-52.
Newton, C. R. J., Hien, T. T. & White, N. 2000. Cerebral malaria. Journal of Neurology,
Neurosurgery & Psychiatry, 69: 433-441.
Nosten, F. O. & White, N. J. 2007. Artemisinin-based combination treatment of falciparum malaria. The American Journal of Tropical Medicine and Hygiene, 77: 181-192. Nothdurft, H. D., Clemens, R., Bock, H. L. & Löscher, T. 1993. Halofantrine: a new
substance for treatment of multidrug-resistant malaria. Journal of Clinical
Investigation, 71: 69-73.
Nzila, A. 2006. The past, present and future of antifolates in the treatment of Plasmodium
falciparum infection. Journal of Antimicrobial Chemotherapy, 57: 1043-1054.
Nzila, A. (2012) Antifolates: pyrimethamine, proguanil, sulphadoxine and dapsone. IN STAINES,H. M. & KRISHNA,S. (Eds.) Treatment and Prevention of Malaria. Springer Basel.
Nzila, A. & Mwai, L. 2010. In vitro selection of Plasmodium falciparum drug-resistant parasite lines. Journal of Antimicrobial Chemotherapy, 65: 390-398.
O‟Neill, P. M., Barton, V. E. & Ward, S. A. 2010. The molecular mechanism of action of artemisinin: the debate continues. Molecules, 15: 1705-1721.
O‟Neill, P. M., Barton, V. E., Ward, S. A. & Chadwick, J. (2012a) 4-Aminoquinolines:
chloroquine, amodiaquine and next-generation analogues. IN STAINES, H. M. &
KRISHNA,S. (Eds.) Treatment and Prevention of Malaria. Springer Basel.
O‟Neill, P. M., Barton, V. E., Ward, S. A. & Chadwick, J. (2012b) Antimalarial drug
chemistry, action and use. IN STAINES, H.M. & KRISHNA, S. (Eds.) Treatment and
Prevention of Malaria. Basel, Springer.
Obonyo, C. O. & Juma, E. A. 2012. Clindamycin plus quinine for treating uncomplicated
falciparum malaria: a systematic review and meta-analysis. Malaria Journal, 11: 2-12.
Ogetii, G., Akech, S., Jemutai, J., Boga, M., Kivaya, E., Fegan, G. & Maitland, K. 2010. Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage. BMC Infectious Diseases, 10: 334.
Oniyangi, O. & Omari, A. A. 2006. Malaria chemoprophylaxis in sickle cell disease.
Cochrane Database of Systematic Reviews, 4: 1-17.
Osonuga, O. A., Osonuga, A. A., Osonuga, I. O., Osonuga, A. & Derkyi, K. L. 2011. Prevalence of hypoglycemia among severe malaria children in a rural African population. Asian Pacific Journal of Tropical Disease, 192-194.
Plebanski, M. & Hill, A. V. S. 2000. The immunology of malaria infection. Current Opinion in
Immunology, 12: 437-441.
Powers, D. G., Casebier, D. S., Fokas, D., Ryan, W. J., Troth, J. R. & Coffen, D. L. 1998. Automated parallel synthesis of chalcone-based screening libraries. Tetrahedron, 54: 4085-4096.
Pybus, B. S., Sousa, J. C., Jin, X., Ferguson, J. A., Christian, R. E., Barnhart, R., Vuong, C., Sciotti, R. J., Reichard, G. A., Kozar, M. P., Walker, L. A., Ohrt, C. & Melendez, V. 2012. CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine. Malaria Journal, 11: 259-267.
Reddy, M. V. B., Su, C. R., Chiou, W. F., Liu, Y. N., Chen, R. Y. H., Bastow, K. F., Lee, K. H. & Wu, T. S. 2008. Design, synthesis, and biological evaluation of mannich bases of heterocyclic chalcone analogs as cytotoxic agents. Bioorganic & Medicinal
Chemistry, 16: 7358-7370.
Reiter, P. 2000. From Shakespeare to Defoe: Malaria in England in the little ice age.
Emerging Infectious Diseases, 6: 1-11.
Rosenthal, P. J. 2004. Cysteine proteases of malaria parasites. International Journal for
Parasitology, 34: 1489-1499.
Sashidhara, K. V., Avula, S. R., Palnati, G. R., Singh, S. V., Srivastava, K., Puri, S. K. & Saxena, J. K. 2012a. Synthesis and in vitro evaluation of new chloroquine-chalcone hybrids against chloroquine-resistant strain of Plasmodium falciparum. Bioorganic &
Sashidhara, K. V., Kumar, M., Modukuri, R. K., Srivastava, R. K., Soni, A., Srivastava, K., Singh, S. V., Saxena, J. K., Gauniyal, H. M. & Puri, S. K. 2012b. Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores.
Bioorganic & Medicinal Chemistry, 20: 2971-2981.
Sasi, P., Burns, S. P., Waruiru, C., English, M., Hobson, C. L., King, C. G., Mosobo, M., Beech, J. S., Iles, R. A., Boucher, B. J. & Cohen, R. D. 2007. Metabolic acidosis and other determinants of hemoglobin-oxygen dissociation in severe childhood
Plasmodium falciparum malaria. The American Journal of Tropical Medicine and Hygiene, 77: 256-260.
Schlagenhauf, P. 1999. Mefloquine for malaria chemoprophylaxis 1992 - 1998: a review.
Journal of Travel Medicine, 6: 122-133.
Schlagenhauf, P., Adamcova, M., Regep, L., Schaerer, M. T., Bansod, S. & Rhein, H. G. 2011. Use of mefloquine in children: a review of dosage, pharmacokinetics and tolerability data. Malaria Journal, 10: 292-302.
Schlitzer, M. 2008. Antimalarial drugs: what is in use and what is in the pipeline. Archiv der
Pharmazie, 341: 149-163.
Sharma, M., Chaturvedi, V., Manju, Y. K., Bhatnagar, S., Srivastava, K., Puri, S. K. & Chauhan, P. M. S. 2009. Substituted quinolinyl chalcones and quinolinyl pyrimidines as a new class of anti-infective agents. European Journal of Medicinal Chemistry, 44: 2081-2091.
Sharma, N., Mohanakrishnan, D., Shard, A., Sharma, A., Saima, Sinha, A. K. & Sahal, D. 2012. Stilbene-chalcone hybrids: design, synthesis, and evaluation as a new class of antimalarial scaffolds that trigger cell death through stage specific apoptosis. Journal
of Medicinal Chemistry, 55: 297-311.
Sijwali, P. S., Kato, K., Seydel, K. B., Gut, J., Lehman, J., Klemba, M., Goldberg, D. E., Miller, L. H. & Rosenthal, P. J. 2004. Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites. Proceedings of the
National Academy of Sciences of the United States of America, 101: 8721-8726.
Singh, C., Chaudhary, S. & Puri, S. K. 2008. Orally active esters of dihydroartemisinin: synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in mice. Bioorganic & Medicinal Chemistry Letters, 18: 1436-1441.
Singh, C., Malik, H. & Puri, S. K. 2005. New orally active spiro 1,2,4-trioxanes with high antimalarial potency. Bioorganic & Medicinal Chemistry Letters, 15: 4484-4487. Srivastava, I. K., Morrisey, J. M., Darrouzet, E., Daldal, F. & Vaidya, A. B. 1999. Resistance
mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Molecular Microbiology, 33: 704-711.
Stanger, O., Fowler, B., Pietrzik, K., Huemer, M., Haschke-Becher, E., Semmler, A., Lorenzl,
S. & Linnebank, M. 2009. Homocysteine, folate and vitamin B12 in neuropsychiatric
Sullivan, D. J. (2012) Cinchona alkaloids: quinine and quinidine. IN STAINES, H. M. & KRISHNA,S. (Eds.) Treatment and Prevention of Malaria. Basel, Springer
Takimoto, C. H. 1996. New antifolates: pharmacology and clinical applications. The
Oncologist, 1: 68-81.
Tan, K. R., Magill, A. J., Parise, M. E. & Arguin, P. M. 2011. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. The American Journal of Tropical Medicine and Hygiene, 84: 517-531.
Targett, G. A., Moorthy, V. S. & Brown, G. V. 2013. Malaria vaccine research and development: the role of the WHO MALVAC committee. Malaria Journal, 12: 362-372.
Testa, B. 2004. Prodrug research: futile or fertile? Biochemical Pharmacology, 68: 2097-2106.
Vaidya, A. B. (2012) Naphthoquinones: atovaquone, and other antimalarials targeting
mitochondrial functions. IN STAINES, H. M. & KRISHNA, S. (Eds.) Treatment and
Prevention of Malaria. Basel, Springer.
Van den Berg, H. 2009. Global status of DDT and its alternatives for use in vector control to prevent disease. Environmental Health Perspectives, 11: 1656-1663.
Van Hellemond, J. J., Rutten, M., Koelewijn, R., Zeeman, A. M., Verweij, J. J., Wismans, P. J., Kocken, C. H. & van Genderen, P. J. J. 2009. Human Plasmodium knowlesi infection detected by rapid diagnostic tests for malaria. Emerging Infectious
Diseases, 15: 1478-1480.
Walsh, J. J. & Bell, A. 2009. Hybrid drugs for malaria. Current Pharmaceutical Design, 15: 2970-2985.
Wambua, S., Mwangi, T. W., Kortok, M., Uyoga, S. M., Macharia, A. W., Mwacharo, J. K., Weatherall, D. J., Snow, R. W., Marsh, K. & Williams, T. N. 2006. The effect of α +-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med, 3: e158.
Waters, N. C. & Edstei, M. D. (2012) 8-Aminoquinolines: primaquine and tafenoquine. IN STAINES, H. M. & KRISHNA, S. (Eds.) Treatment and Prevention of Malaria. Basel, Springer.
WHO. 2010. Guidelines for treatment of malaria: 2nd Edition. [WEB]:
http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf. [Date of access: January 2013].
WHO. 2012. World malaria report 2012. [WEB]:
http://www.who.int/malaria/publications/world_malaria_report_2012/wmr2012_countr y_profiles.pdf. [Date of access: March 2013].
WHO. 2013. Emergency response to artemisinin resistance in the greater Mekong
subregion. [WEB]:
http://apps.who.int/iris/bitstream/10665/79940/1/9789241505321_eng.pdf. [Date of access: November 2013].
Wongsrichanalai, C., Barcus, M. J., Muth, S., Sutamihardja, A. & Wernsdorfer, W. H. 2007. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). The
American Journal of Tropical Medicine and Hygiene, 77: 119-127.
Wongsrichanalai, C., Pickard, A. L., Wernsdorfer, W. H. & Meshnick, S. R. 2002. Epidemiology of drug-resistant malaria. The Lancet Infectious Diseases, 2: 209-218. Wu, X., Tiekink, E. R. T., Kostetski, I., Kocherginsky, N., Tan, A. L. C., Khoo, S. B., Wilairat,
P. & Go, M. L. 2006. Antiplasmodial activity of ferrocenyl chalcones: investigations into the role of ferrocene. European Journal of Pharmaceutical Sciences, 27: 175-187.
Wu, X., Wilairat, P. & Go, M. L. 2002. Antimalarial activity of ferrocenyl chalcones.
Bioorganic & Medicinal Chemistry Letters, 12: 2299-2302.
Xie, L., Zhai, X., Ren, L., Meng, H., Liu, C., Zhu, W. & Zhao, Y. 2011. Design, synthesis and antitumor activity of novel artemisinin derivatives using hybrid approach.
Chemical and Pharmaceutical Bulletin, 59: 984-990.
Yadav, N., Dixit, S. K., Bhattacharya, A., Mishra, L. C., Sharma, M., Awasthi, S. K. & Bhasin, V. K. 2012. Antimalarial activity of newly synthesized chalcone derivatives in vitro.
Chemical Biology & Drug Design, 80: 340-347.
Zheng, C. J., Jiang, S. M., Chen, Z. H., Ye, B. J. & Piao, H. R. 2011. Synthesis and anti-bacterial activity of some heterocyclic chalcone derivatives bearing thiofuran, furan, and quinoline moieties. Archiv der Pharmazie, 344: 689-695.
Addendum A: Analytical data for Chapter 3
_________________________________________________________________________ IR: 10 O HO O O 101H NMR in DMSO: 10 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 ppm 2 .3 3 2 .3 7 2 .4 0 2 .4 9 2 .4 9 2 .4 9 2 .5 0 3 .0 8 3 .1 5 3 .3 7 5 .7 4 6 .4 4 6 .4 4 6 .4 4 6 .4 4 7 .7 0 7 .7 1 7 .7 3 7 .7 4 7 .7 6 7 .7 7 7 .8 0 7 .8 0 7 .8 4 7 .8 9 7 .9 1 7 .9 2 7 .9 3 7 .9 4 7 .9 7 7 .9 8 7 .9 9 8 .0 0 8 .0 1 8 .1 1 1 0 .0 9 1 3 .1 4 1 3 .1 5 1 8 .7 1 5 .3 4 1 .8 2 1 4 .3 5 5 .9 8 1 .0 8 1 0 .4 5 1 .1 6 6 .4 9 1 2 .6 2 1 2 .6 1 5 .5 4 7.70 7.75 7.80 7.85 7.90 7.95 8.00 8.05 ppm 7 .7 0 7 .7 1 7 .7 3 7 .7 4 7 .7 6 7 .7 7 7 .8 0 7 .8 0 7 .8 4 7 .8 9 7 .9 1 7 .9 2 7 .9 3 7 .9 4 7 .9 7 7 .9 8 7 .9 9 8 .0 0 8 .0 1 1 .0 8 1 0 .4 5 1 .1 6 6 .4 9 1 2 .6 2 1 2 .6 1 13 C NMR in DMSO: 10 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 1 3 .7 7 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 0 .0 4 4 8 .6 1 1 0 9 .6 5 1 2 2 .0 3 1 2 4 .1 7 1 2 8 .7 4 1 2 9 .7 4 1 2 9 .9 4 1 3 1 .9 9 1 3 8 .6 6 1 4 0 .7 6 1 5 1 .8 3 1 5 8 .9 8 1 6 6 .8 7 1 7 5 .4 7 O HO O O 1 2 3 1' 2' 3' 4' 5' 6' a 10 1" 2" 2" 3" 3" 4" 5" O HO O O 1 2 3 1' 2' 3' 4' 5' 6' a 10 1" 2" 2" 3" 3" 4" 5" a 4‟ 2” 3” 3‟ 2 1 2 H2O 6‟ 3 5” 2‟ 5‟ 1 1” 4” 2” 3” 2 2 4‟ 6‟ 4‟ 6‟ 3 5” 3” 2” 1 a 2” 3” 4‟ 2‟ 5‟ 4” 1” 3‟
DEPT135 in DMSO: 10 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .7 7 3 9 .3 4 3 9 .4 8 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 0 .0 3 5 9 .3 9 1 0 9 .6 5 1 2 2 .0 4 1 2 4 .1 6 1 2 8 .7 5 1 2 9 .7 4 1 4 0 .7 6 1 5 8 .9 8 COSY in DMSO: 10 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 ppm 13 12 11 10 9 8 7 6 5 4 3 2 1 O HO O O 10 O HO O O 10
HSQC in DMSO: 10 ppm 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 HRMS: 10 O HO O O 10 O HO O O 10
131 IR: 11 1H NMR in DMSO: 11 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 1 .0 3 1 .0 4 1 .0 5 2 .4 0 2 .4 9 2 .4 9 2 .4 9 3 .3 7 3 .4 1 3 .4 2 3 .4 2 3 .4 3 3 .4 4 3 .4 5 3 .4 8 3 .4 9 3 .5 3 3 .5 4 3 .5 5 4 .3 6 4 .3 7 4 .3 8 6 .4 5 6 .4 5 6 .6 4 6 .6 4 7 .4 5 7 .4 5 7 .4 6 7 .4 7 7 .5 1 7 .7 2 7 .7 3 7 .7 8 7 .7 8 7 .7 9 7 .8 0 7 .8 9 7 .9 1 7 .9 2 7 .9 4 8 .2 0 8 .2 1 8 .4 0 8 .4 1 8 .8 2 9 .4 2 8 .6 7 6 5 .3 6 3 .5 1 0 .7 6 0 .9 0 0 .8 9 0 .8 7 1 .6 4 1 .6 6 3 .2 7 0 .9 5 0 .9 2 0 .8 7 O H N O O N H N Cl 11 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 11 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b OH of EtOH H2O DMSO EtOH amide 2a 5a 2” 3” 3‟, 8a 1, 2 NH, 6a 3a 4‟ OH of EtOH EtOH 2b 1b H2O 6‟ EtOH
13C NMR in DMSO: 11 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .7 9 1 8 .5 7 3 7 .9 7 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 0 .0 4 4 1 .9 1 5 6 .0 6 9 8 .7 0 1 0 9 .6 3 1 1 7 .7 1 1 2 1 .9 5 1 2 3 .5 4 1 2 3 .9 6 1 2 4 .2 2 1 2 7 .5 4 1 2 7 .7 4 1 2 8 .6 2 1 3 3 .4 7 1 3 5 .5 7 1 3 7 .2 1 1 4 1 .0 0 1 5 0 .3 5 1 5 1 .8 6 1 5 1 .9 6 1 5 9 .0 8 1 6 6 .2 2 1 7 5 .5 7 DEPT135 in DMSO: 11 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 ppm 1 3 .7 9 1 8 .5 7 3 7 .9 7 3 9 .4 7 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 1 .9 0 5 6 .0 5 9 8 .6 9 1 0 9 .6 3 1 2 1 .9 5 1 2 3 .5 3 1 2 3 .9 6 1 2 4 .2 2 1 2 7 .5 4 1 2 7 .7 4 1 2 8 .6 2 1 4 1 .0 0 1 5 1 .9 6 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 11 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3 5” 2‟ 2a, 5‟ 9a 1 1” 4” 7a 2” 3” 8a 6a, 5a, 2 3a 10a 4‟ EtOH 2b 1b EtOH 6‟ EtOH 6‟ 1b 2b O H N O O N H N Cl 11
COSY in DMSO: 11 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 HSQC in DMSO: 12 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O H N O O N H N Cl 11 O H N O O N H N Cl 11
HRMS: 11 O H N O O N H N Cl 11
IR: 12 1H NMR in DMSO: 12 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 1 .9 3 2 .4 0 2 .4 9 3 .3 8 6 .4 4 6 .4 8 7 .3 7 7 .4 3 7 .4 5 7 .7 2 7 .7 7 7 .7 9 7 .9 1 8 .2 5 8 .2 6 8 .3 8 8 .6 6 4 .8 9 7 .0 1 4 1 .5 8 4 .4 6 4 .8 9 1 9 .7 1 2 .5 0 2 .4 8 2 .4 5 O H N O O H N N Cl 12 O H N O O H N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 12 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b amide 2a 5a 3” 2” 3‟, 8a 1, 2 6a, NH 3a, 4‟ 1b 3b 6‟ 2b
13C NMR in DMSO: 12 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 185 ppm 1 3 .7 7 2 7 .8 1 3 7 .3 2 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 0 .1 6 9 8 .7 0 1 0 9 .6 0 1 1 7 .4 8 1 2 1 .8 9 1 2 3 .4 4 1 2 4 .0 3 1 2 4 .1 1 1 2 7 .4 5 1 2 7 .6 9 1 2 8 .5 7 1 3 3 .4 5 1 3 5 .7 9 1 3 7 .0 5 1 4 1 .0 4 1 4 9 .0 1 1 5 0 .0 7 1 5 1 .8 5 1 5 8 .8 9 1 6 5 .7 8 1 7 5 .5 7 DEPT135 in DMSO: 12 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 ppm 1 3 .7 7 2 7 .8 0 3 7 .3 2 3 9 .4 8 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 0 .1 6 9 8 .6 9 1 0 9 .6 0 1 2 1 .9 0 1 2 3 .4 3 1 2 4 .0 3 1 2 4 .1 1 1 2 7 .4 4 1 2 7 .6 9 1 2 8 .5 7 1 4 1 .0 4 1 5 1 .8 5 O H N O O H N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 12 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 3 5” 2‟ 2a 5‟ 9a 1 1” 4” 7a 2” 3” 8a 6a, 5a 2 10a 4‟ 3a 1b 3b 2b 6‟ O H N O O H N N Cl 12
COSY in DMSO: 12 ppm 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 HSQC in DMSO: 12 ppm 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O H N O O H N N Cl 12 O H N O O H N N Cl 12
HRMS: 12 O H N O O H N N Cl 12
IR: 13 1H NMR in DMSO: 13 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 1 .6 8 1 .6 9 1 .7 0 1 .7 2 1 .7 3 1 .7 4 1 .7 5 2 .4 1 2 .5 0 2 .5 0 3 .3 3 3 .3 4 3 .3 5 3 .3 6 3 .3 9 3 .4 1 3 .4 2 3 .4 3 6 .4 5 6 .4 6 6 .6 4 6 .6 5 7 .5 4 7 .5 5 7 .5 6 7 .5 6 7 .7 0 7 .7 3 7 .7 3 7 .7 6 7 .8 1 7 .8 2 7 .8 5 7 .8 5 7 .8 9 7 .9 1 7 .9 1 7 .9 3 8 .2 2 8 .4 1 8 .4 2 8 .4 3 8 .6 4 8 .6 5 1 0 .6 2 7 .3 8 4 5 .9 0 2 .1 4 2 .5 0 2 .2 4 5 .0 1 2 .3 7 2 .6 1 9 .4 0 2 .3 9 4 .9 0 2 .5 3 O H N O O N H N Cl 13 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 13 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b amide 8a, 2a NH 2”, 3” 1, 2 5a, 3‟ 6a 3a 4‟ H2O 1b 4b 6‟ 3b 2b
13C NMR in DMSO: 13 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .7 8 2 5 .1 7 2 6 .6 9 3 8 .8 7 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 0 .0 4 4 2 .4 4 9 8 .6 4 1 0 9 .6 1 1 1 6 .6 6 1 2 1 .9 2 1 2 3 .4 1 1 2 4 .1 3 1 2 4 .7 9 1 2 5 .0 9 1 2 7 .6 7 1 2 8 .5 5 1 3 5 .1 8 1 3 5 .8 2 1 3 6 .9 9 1 4 1 .0 5 1 4 8 .2 8 1 5 1 .8 5 1 5 2 .1 8 1 5 8 .9 0 1 6 5 .5 4 1 7 5 .5 7 DEPT135 in DMSO: 13 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 ppm 1 3 .7 8 2 5 .1 6 2 6 .6 8 3 8 .8 7 3 9 .7 5 4 2 .4 3 9 8 .6 4 1 0 9 .6 1 1 2 1 .9 3 1 2 3 .4 1 1 2 4 .1 3 1 2 4 .7 9 1 2 5 .0 9 1 2 7 .6 7 1 2 8 .5 5 1 4 1 .0 5 1 4 8 .2 7 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 13 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 3 5” 2‟ 5‟ 9a 1 2a 1” 4” 7a 2” 3” 5a, 6a, 1 2 3‟ 10a 4‟ 3a 1b 4b 2b 3b 6‟ O H N O O N H N Cl 13
COSY in DMSO: 13 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 HSQC in DMSO: 13 ppm 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O H N O O N H N Cl 13 O H N O O N H N Cl 13
HRMS: 13 O H N O O N H N Cl 13
IR: 14 1H NMR in DMSO: 14 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 1 .2 6 1 .3 7 1 .3 8 1 .3 9 1 .4 0 2 .3 3 2 .4 3 3 .3 0 3 .3 1 3 .3 1 3 .3 1 3 .3 2 3 .4 5 3 .4 6 3 .4 6 3 .4 8 3 .4 9 3 .5 4 3 .5 5 3 .5 6 3 .5 7 3 .5 9 4 .5 0 4 .5 2 4 .5 3 4 .5 4 4 .5 5 4 .9 0 6 .3 4 6 .3 4 6 .3 5 6 .3 5 6 .7 4 6 .7 5 7 .3 8 7 .3 8 7 .4 0 7 .4 0 7 .5 3 7 .5 4 7 .5 7 7 .6 0 7 .7 4 7 .7 4 7 .7 5 7 .7 7 7 .8 2 7 .8 3 8 .0 4 8 .0 5 8 .3 3 8 .3 4 8 .7 5 1 .7 6 6 .2 8 2 .7 5 2 .9 2 2 .7 2 1 .9 9 2 .4 0 2 .7 4 2 .0 7 2 .3 6 9 .1 9 4 .3 2 2 .4 4 2 .5 3 14 O H N O O N H N Cl O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 14 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b2b 3b 2a 5a 3” 2 2” 8a 1 3‟ 4‟ 3a 6a H2O 2b 1b MeOD 6‟ 3b
13C NMR in DMSO: 14 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 185 ppm 1 3 .9 1 1 8 .0 9 4 6 .4 4 4 8 .5 8 4 8 .7 2 4 8 .8 6 4 9 .0 0 4 9 .1 4 4 9 .2 8 4 9 .4 3 4 9 .6 8 9 9 .9 2 1 1 0 .8 0 1 1 8 .5 4 1 2 2 .7 7 1 2 4 .2 2 1 2 4 .2 8 1 2 6 .3 0 1 2 7 .1 2 1 2 8 .1 7 1 2 9 .0 6 1 2 9 .6 3 1 3 0 .8 2 1 3 6 .6 7 1 3 7 .0 2 1 3 9 .1 8 1 4 1 .5 7 1 4 3 .1 0 1 4 8 .9 7 1 5 1 .8 2 1 5 3 .1 0 1 5 3 .5 2 1 6 0 .9 1 1 6 9 .9 0 1 7 8 .4 4 DEPT135 in DMSO: 14 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 ppm 1 8 .1 0 4 6 .4 5 4 8 .8 7 4 9 .0 1 4 9 .1 5 4 9 .3 0 9 9 .9 2 1 1 0 .6 3 1 1 0 .8 1 1 2 2 .7 8 1 2 4 .2 2 1 2 4 .2 8 1 2 6 .3 0 1 2 7 .0 0 1 2 7 .1 2 1 2 8 .1 8 1 2 9 .0 7 1 2 9 .6 4 1 3 0 .8 2 1 4 1 .5 7 1 4 3 .1 1 1 5 1 .8 3 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 14 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b2b 3b 3 5” 2‟ 5‟ 2a 9a 4a 1 1” 4” 7a 2” 3” 5a 3‟ 10a 4‟ 3a 8a, 2, 6a 2b 1b 3b 6‟ 14 O H N O O N H N Cl
COSY in DMSO: 14 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 HSQC in DMSO: 14 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 14 O H N O O N H N Cl 14 O H N O O N H N Cl
14 O H N O O N H N Cl
IR: 15 1H NMR in DMSO: 15 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 1 .3 6 1 .3 7 1 .3 8 1 .3 9 1 .4 0 1 .4 1 1 .4 2 1 .4 3 1 .5 1 1 .5 3 1 .5 4 1 .5 5 1 .5 6 1 .6 3 1 .6 4 1 .6 5 1 .6 6 1 .6 7 2 .4 0 2 .4 9 2 .4 9 2 .4 9 3 .2 4 3 .2 5 3 .2 6 3 .2 6 3 .2 7 3 .2 8 6 .4 4 6 .4 4 6 .4 4 6 .4 6 6 .4 7 7 .4 3 7 .4 4 7 .4 5 7 .4 5 7 .4 9 7 .5 0 7 .5 1 7 .6 8 7 .7 1 7 .7 1 7 .7 4 7 .7 7 7 .7 7 7 .7 9 7 .7 9 7 .8 7 7 .8 8 7 .8 9 7 .9 0 8 .2 8 8 .2 9 8 .3 6 8 .3 7 8 .5 6 8 .5 7 4 .2 9 2 .0 0 1 .9 8 2 .7 9 3 .9 7 0 .8 9 1 .0 1 1 .0 0 0 .9 4 1 .9 2 1 .9 8 3 .7 0 1 .0 1 1 .0 0 0 .9 0 O H N O O N H N Cl 15 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 15 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 6b 5b amide 2a 5a 2” 3” 3‟, 8a 1 2 NH 6a 3a 4‟ H2O 6b, 1b 6‟ DMSO 2b 5b 3b, 4b
13C NMR in DMSO: 15 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .8 4 2 6 .3 7 2 6 .4 3 2 7 .7 8 2 9 .1 5 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 0 .0 3 4 2 .5 0 9 8 .6 6 1 0 9 .6 9 1 1 7 .3 0 1 2 2 .0 0 1 2 3 .4 2 1 2 4 .3 3 1 2 4 .3 6 1 2 6 .6 4 1 2 7 .7 3 1 2 8 .6 2 1 3 3 .9 2 1 3 5 .9 7 1 3 7 .0 1 1 4 1 .1 4 1 4 8 .0 4 1 5 0 .7 2 1 5 1 .0 8 1 5 1 .9 0 1 5 9 .0 0 1 6 5 .5 6 1 7 5 .6 4 DEPT135 in DMSO: 15 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 ppm 2 6 .3 6 2 6 .4 3 2 7 .7 9 2 9 .1 5 3 9 .3 0 4 2 .4 9 9 8 .6 6 1 0 9 .6 9 1 2 2 .0 0 1 2 3 .4 2 1 2 4 .3 4 1 2 4 .3 6 1 2 6 .6 4 1 2 7 .7 3 1 2 8 .6 2 1 4 1 .1 4 1 5 1 .0 8 O H N O O N H N Cl 1 2 3 1' 2' 3' 4' 5' 6' 15 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 6b 5b 3 5” 2‟ 9a 2a, 5 4a 1 1” 4” 7a 2” 3” 8a 5a, 6a 2a 3‟ 10a 4‟ 3a 1b 6b 5b 2b 3b, 4b 6‟ O H N O O N H N Cl 15
COSY in DMSO: 15 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 HSQC in DMSO: 15 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O H N O O N H N Cl 15 O H N O O N H N Cl 15
HRMS: 15 O H N O O N H N Cl 15
IR: 16 1H NMR in DMSO: 16 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 1 .9 5 1 .9 6 2 .4 3 3 .0 0 3 .4 2 3 .4 2 3 .6 6 3 .6 7 3 .6 8 6 .2 1 6 .2 2 6 .3 9 6 .4 0 6 .9 2 7 .2 4 7 .2 6 7 .2 6 7 .3 1 7 .3 2 7 .3 9 7 .4 2 7 .4 4 7 .4 5 7 .6 7 7 .6 8 7 .8 0 7 .8 3 7 .9 1 7 .9 8 8 .0 0 8 .4 6 8 .4 7 6 .0 3 8 .0 6 8 .4 4 6 .7 8 5 .6 5 2 .9 2 2 .6 7 2 .6 1 1 6 .1 7 5 .6 0 2 .5 8 2 .9 5 2 .6 5 3 .0 0 16 O N O O H N N Cl O N O O H N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 16 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 2a 5a 8a 1 2” 3” 2 6a 3‟ CDCl3 3 NH 3a 4‟ 3b 1b 4b 6‟ 2b
13C NMR in DMSO: 16 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 4 .2 0 2 4 .7 5 3 7 .4 7 3 8 .7 3 4 4 .4 2 7 6 .7 9 7 7 .0 0 7 7 .2 1 9 8 .1 7 1 0 9 .5 1 1 1 7 .5 2 1 1 9 .9 8 1 2 2 .1 7 1 2 2 .6 4 1 2 5 .4 6 1 2 7 .4 4 1 2 7 .8 3 1 2 8 .5 1 1 3 5 .1 4 1 3 6 .4 0 1 3 7 .2 3 1 4 1 .7 7 1 5 0 .1 9 1 5 1 .2 7 1 5 2 .3 2 1 5 8 .5 0 1 7 1 .9 5 1 7 6 .8 1 DEPT135 in DMSO: 16 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 ppm 2 4 .7 5 3 7 .4 8 3 8 .6 5 3 8 .7 3 4 4 .4 2 9 8 .1 7 1 0 9 .5 1 1 1 9 .9 9 1 2 2 .1 7 1 2 2 .6 4 1 2 5 .4 6 1 2 7 .4 5 1 2 7 .8 3 1 2 8 .5 2 1 4 1 .7 7 1 5 1 .2 9 O N O O H N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 16 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 3 5” 2‟ 5‟ 2a 9a 1 1” 7a 4” 2” 3” 8a 6a 5a 2 3‟ 10a 4‟ 3a 3b 1b 4b 2b 6‟ 16 O N O O H N N Cl
COSY in DMSO: 16 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 HSQC in DMSO: 16 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 16 O N O O H N N Cl 16 O N O O H N N Cl
HRMS: 16 16 O N O O H N N Cl
IR: 17 1H NMR in DMSO: 17 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 2 .4 1 3 .3 9 3 .4 0 3 .4 5 3 .6 4 3 .6 5 3 .6 6 3 .6 7 3 .6 8 3 .6 9 3 .7 7 3 .7 8 3 .7 9 5 .7 3 6 .2 0 6 .2 1 6 .2 7 6 .2 8 6 .9 6 6 .9 7 7 .2 2 7 .2 3 7 .2 4 7 .2 6 7 .2 6 7 .3 1 7 .3 3 7 .4 9 7 .5 1 7 .6 8 7 .6 9 7 .7 1 7 .7 3 7 .8 5 7 .8 6 8 .4 0 8 .4 1 7 .6 5 5 .0 9 1 .3 5 2 1 .6 0 5 .5 9 2 .5 2 2 .4 3 2 .5 4 2 .4 2 5 .7 9 2 .6 0 5 .2 5 1 0 .4 5 2 .6 5 2 .5 9 O H N O O O O N H N Cl 17 17 1" 2" 2" 3" O H N O O O O N H N Cl 6' 5' 4' 3' 2' 1' 3 2 1 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 5b 6b 2a 8a 1 2” 5a 3” 2 CDCl3 6a amide 3‟ 3a 4‟ NH 2b 3b, 4b 5b, 6b 1b 6‟
13C NMR in DMSO: 17 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 185 190 ppm 1 4 .1 9 3 9 .7 3 4 2 .6 2 6 8 .6 0 6 9 .7 8 7 0 .0 7 7 0 .2 0 7 6 .7 9 7 7 .0 0 7 7 .2 1 9 9 .0 2 1 0 9 .5 1 1 1 7 .1 7 1 2 0 .1 3 1 2 1 .3 5 1 2 2 .8 3 1 2 5 .2 9 1 2 7 .4 5 1 2 8 .1 9 1 2 8 .2 8 1 2 8 .7 4 1 3 4 .9 6 1 3 5 .5 5 1 3 7 .6 0 1 4 1 .6 1 1 4 8 .6 2 1 4 9 .8 7 1 5 1 .5 1 1 5 2 .2 7 1 5 8 .5 5 1 6 6 .8 1 1 7 6 .7 7 DEPT135 in DMSO: 17 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 ppm 3 9 .7 3 4 2 .6 2 6 8 .6 0 6 9 .7 9 7 0 .0 7 7 0 .2 0 9 9 .0 2 1 0 9 .5 2 1 2 0 .1 3 1 2 1 .3 5 1 2 2 .8 3 1 2 5 .2 9 1 2 7 .4 5 1 2 8 .2 0 1 2 8 .2 8 1 4 1 .6 1 1 5 1 .5 1 17 1" 2" 2" 3" O H N O O O O N H N Cl 6' 5' 4' 3' 2' 1' 3 2 1 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 5b 6b 3 5” 2‟ 4a 2a 9a 5‟ 1 1” 4” 7a 2” 3” 6a 2 5a 3‟ 10a 4‟ 3a 3b, 4b, 5b 2b 1b 6b 6‟ O H N O O O O N H N Cl 17
COSY in DMSO: 17 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 HSQC in DMSO: 17 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O H N O O O O N H N Cl 17 O H N O O O O N H N Cl 17
O H N O O O O N H N Cl 17
IR: 18 1H NMR in CDCl 3: 18 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 1 .8 1 1 .8 2 1 .8 4 1 .8 5 1 .8 6 1 .8 7 1 .8 8 2 .2 8 2 .3 0 2 .3 2 2 .3 4 2 .4 1 2 .5 1 2 .5 2 2 .5 3 2 .5 5 2 .5 6 2 .5 7 3 .3 0 3 .3 1 3 .4 5 3 .5 0 3 .5 1 6 .2 0 6 .2 0 6 .2 1 6 .2 2 6 .9 7 7 .1 8 7 .1 9 7 .2 0 7 .2 0 7 .2 3 7 .2 4 7 .3 2 7 .3 4 7 .3 9 7 .4 0 7 .5 6 7 .5 7 7 .5 9 7 .7 1 7 .7 2 7 .7 5 7 .8 2 7 .8 3 8 .3 8 8 .3 9 9 .6 1 9 .3 2 7 .3 1 9 .3 3 4 .7 6 4 .3 1 4 .2 9 2 .0 6 5 .9 5 2 .1 2 2 .1 7 6 .2 8 6 .0 8 2 .2 9 2 .3 0 18 O H N O O N H N N Cl O H N O O N H N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 18 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 5b 6b 7b 2a 8a 1 2” 3” 5a amide 2 CDCl3 3‟ 6a NH 3a, 4‟ 6b 1b 3b 2b 5b 4b 6‟ 7b
13C NMR in CDCl 3: 18 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 1 4 .1 9 2 4 .9 5 2 6 .8 6 3 9 .1 0 4 2 .0 9 4 3 .0 1 5 6 .4 2 5 6 .9 1 7 6 .7 9 7 7 .0 0 7 7 .2 1 9 8 .5 0 1 0 9 .5 1 1 1 7 .3 7 1 2 0 .0 9 1 2 1 .5 9 1 2 2 .7 9 1 2 4 .9 1 1 2 7 .4 2 1 2 8 .3 7 1 3 4 .6 2 1 3 5 .8 3 1 3 7 .5 6 1 4 1 .6 4 1 4 8 .9 3 1 5 0 .2 1 1 5 1 .8 6 1 5 2 .2 7 1 5 8 .5 5 1 6 6 .7 8 1 7 6 .7 7 DEPT in CDCl3: 18 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 ppm 2 4 .9 5 3 9 .0 9 4 2 .0 9 4 3 .0 1 5 6 .9 0 9 8 .5 0 1 0 9 .5 1 1 2 0 .0 9 1 2 1 .5 9 1 2 2 .7 8 1 2 4 .9 0 1 2 7 .4 2 1 2 8 .3 2 1 2 8 .3 7 1 4 1 .6 4 1 5 1 .8 6 O H N O O N H N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 18 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 2b 3b 4b 5b 6b 7b 3 5” 2‟ 4a 9a 2a 5‟ 1 1” 4” 7a 3” 2” 6a 2 8a 3‟ 10a 4‟ 3a 3b 4b 1b 7b 6b 5b 2b 6‟ 18 O H N O O N H N N Cl
COSY in CDCl3: 18 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 HSQC in CDCl3: 18 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 18 O H N O O N H N N Cl 18 O H N O O N H N N Cl
HRMS: 18 18 O H N O O N H N N Cl
IR: 19 1H NMR in CDCl 3: 19 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 2 .4 2 3 .1 5 3 .2 6 3 .4 8 3 .7 3 4 .0 5 6 .2 1 6 .2 1 6 .8 2 6 .8 3 7 .2 4 7 .2 5 7 .2 5 7 .3 9 7 .4 1 7 .4 3 7 .4 3 7 .4 8 7 .4 9 7 .6 7 7 .6 9 7 .7 9 7 .8 2 7 .9 1 7 .9 2 7 .9 7 7 .9 9 8 .0 3 8 .0 3 8 .0 5 8 .0 5 8 .7 1 8 .7 2 8 .7 5 8 .7 6 8 .0 3 1 5 .8 4 1 2 .1 6 2 .5 6 2 .7 9 3 .3 8 6 .5 6 5 .5 2 5 .6 2 2 .7 1 2 .9 7 2 .5 2 2 .7 9 O O O N N N Cl 19 O O O N N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 19 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 1b 2b 2b 2a 8a 5a 1 2” 3” 6a 2 3‟ 3a 4‟ 1b 6‟
13C NMR in CDCl 3: 19 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 ppm 1 4 .1 8 5 2 .1 3 7 6 .7 9 7 7 .0 0 7 7 .2 1 1 0 9 .3 5 1 0 9 .4 9 1 1 9 .9 1 1 2 1 .7 4 1 2 2 .6 4 1 2 4 .6 3 1 2 6 .6 2 1 2 7 .7 7 1 2 8 .5 2 1 2 9 .0 2 1 3 5 .1 6 1 3 6 .5 0 1 3 6 .7 5 1 4 1 .7 5 1 5 0 .0 9 1 5 1 .9 0 1 5 2 .3 3 1 5 6 .2 3 1 5 8 .4 5 1 6 9 .8 0 1 7 6 .7 9 DEPT135 in CDCl3: 19 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 ppm 1 4 .1 8 5 2 .1 2 1 0 9 .3 4 1 0 9 .4 9 1 1 9 .9 1 1 2 2 .6 3 1 2 4 .6 2 1 2 6 .6 2 1 2 7 .7 6 1 2 8 .5 2 1 2 9 .0 2 1 4 1 .7 5 1 5 1 .9 0 O O O N N N Cl 1 2 3 1' 2' 3' 4' 5' 6' 19 1" 2" 2" 3" 3" 4" 5" 2a 3a 4a 5a 6a 7a 8a 1b 1b 2b 2b 3 5” 2‟ 4a 9a 2a 5‟ 1 1” 7a 4” 8a 2” 3” 5a 2 6a 10a 3‟ 3a 4‟ 7” 6‟ O O O N N N Cl 19
COSY in CDCl3: 19 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 HSQC in CDCl3: 19 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 O O O N N N Cl 19 O O O N N N Cl 19
HRMS: 19 O O O N N N Cl 19
IR: 20 1H NMR in DMSO: 20 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 2 .4 0 2 .4 9 3 .4 0 6 .4 4 6 .4 5 7 .4 6 7 .4 7 7 .6 9 7 .7 2 7 .7 3 7 .7 6 7 .8 0 7 .8 1 7 .9 0 7 .9 2 7 .9 2 7 .9 4 8 .0 7 1 2 .3 7 2 3 .8 7 1 2 .8 7 3 .8 7 3 .8 4 8 .3 7 4 .6 8 1 5 .1 2 4 .3 6 6”-α 2” 3” 3‟ 1 2 6”-β 4‟ H2O 6‟ DMSO O O H2N O 20 O O H2N O 1' 5' 6' 1 2 3 2' 3' 1'' 2'' 3'' 4'' 5'' 4' 6'' 20
13C NMR in DMSO: 20 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .7 6 1 0 9 .5 8 1 2 1 .9 0 1 2 3 .4 6 1 2 7 .9 7 1 2 8 .5 1 1 3 5 .5 2 1 3 7 .1 4 1 4 1 .0 3 1 5 1 .8 5 1 5 8 .8 7 1 6 7 .2 2 1 7 5 .5 5 DEPT135 in DMSO: 20 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 ppm 1 3 .7 6 3 9 .4 8 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 0 .0 3 1 0 9 .5 9 1 2 1 .9 1 1 2 3 .4 5 1 2 7 .4 8 1 2 7 .9 7 1 2 8 .5 2 1 2 9 .2 8 1 3 2 .7 3 1 4 1 .0 3 3 5” 2‟ 5‟ 1 1” 4” 2” 3” 2 3‟ 4‟ 6‟ O O H2N O 1' 5' 6' 1 2 3 2' 3' 1'' 2'' 3'' 4'' 5'' 4' 6'' 20 O O H2N O 20
COSY in DMSO: 20 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 HSQC in DMSO: 20 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O O H2N O 20 O O H2N O 20
HRMS: 20
O O H2N
IR: 21 1H NMR in CDCl 3: 21 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm 0 .9 0 0 .9 2 0 .9 3 1 .3 4 1 .3 6 1 .3 7 1 .3 8 1 .3 9 1 .4 1 1 .5 5 1 .5 6 1 .5 7 1 .5 7 1 .5 8 1 .6 0 2 .4 1 3 .4 0 3 .4 1 3 .4 2 3 .4 3 3 .4 4 6 .1 9 6 .2 0 6 .2 0 6 .3 6 6 .3 6 6 .3 7 7 .2 3 7 .2 4 7 .3 7 7 .3 9 7 .6 1 7 .6 3 7 .7 6 7 .7 7 7 .7 9 1 2 .7 7 8 .8 2 8 .5 1 1 2 .0 5 8 .3 9 3 .8 6 3 .9 3 4 .5 9 4 .2 6 8 .1 9 1 1 .9 6 2” 1 3” 2 3‟ 6” 4‟ 7” 6‟ 8” 9” 10” O O O H N 21 7'' 8'' 9'' 10'' O O O H N 1' 5' 6' 1 2 3 2' 3' 1'' 2'' 3'' 4'' 5'' 4' 6'' 21
13C NMR in CDCl 3: 21 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 ppm 1 3 .7 4 1 4 .1 7 2 0 .1 2 3 1 .6 4 3 9 .8 7 1 0 9 .4 8 1 1 9 .9 8 1 2 2 .7 5 1 2 7 .4 4 1 2 8 .4 0 1 3 6 .1 3 1 3 7 .5 0 1 4 1 .7 9 1 5 2 .3 1 1 5 8 .4 9 1 6 6 .7 1 1 7 6 .8 2 DEPT135 in CDCl3: 21 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 ppm 1 3 .7 5 1 4 .1 7 1 4 .2 0 2 0 .1 2 3 1 .6 4 3 9 .8 7 6 8 .1 0 1 0 9 .4 8 1 1 9 .9 9 1 2 2 .7 4 1 2 6 .7 0 1 2 7 .1 4 1 2 7 .4 4 1 2 8 .4 0 1 4 1 .7 9 3 5” 2‟ 5‟ 1 1” 4” 2” 3” 2 3‟ 4‟ 7” 8” 9” 10” 6‟ 7'' 8'' 9'' 10'' O O O H N 1' 5' 6' 1 2 3 2' 3' 1'' 2'' 3'' 4'' 5'' 4' 6'' 21 O O O H N 21
COSY in CDCl3: 21 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 HSQC in CDCl3: 21 ppm 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 O O O H N 21 O O O H N 21
HRMS: 21 O O O H N 21
IR: 22 1 H NMR in CDCl3: 22 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 ppm 1 .0 5 1 .0 6 1 .0 7 1 .7 2 2 .0 0 2 .1 7 2 .2 2 2 .2 8 2 .3 9 3 .2 9 3 .4 7 3 .5 1 3 .5 3 3 .5 4 3 .5 5 3 .6 2 6 .0 6 6 .0 7 6 .0 7 7 .1 1 7 .1 1 7 .2 1 7 .2 4 7 .2 7 7 .2 8 7 .2 9 7 .5 1 7 .5 2 7 .6 4 7 .6 7 1 4 .6 2 4 1 .0 4 4 .8 1 5 .5 4 1 4 .7 7 9 .7 7 4 .7 4 1 2” 3” 3‟ 2 4‟ 6” 7” 6‟ O O O N O 1' 5' 6' 1 2 3 2' 3' 1'' 2'' 3'' 4'' 5'' 4' 6'' 7'' 22 O O O N O 22
13C NMR in CDCl 3: 22 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 4 .1 5 4 2 .4 7 4 8 .1 0 6 6 .7 7 7 6 .7 9 7 7 .0 0 7 7 .2 1 1 0 9 .4 3 1 1 9 .8 5 1 2 2 .5 1 1 2 7 .6 9 1 2 8 .4 3 1 3 6 .3 0 1 3 6 .7 3 1 4 1 .7 8 1 5 2 .3 0 1 5 8 .3 9 1 6 9 .5 7 1 7 6 .7 7 HRMS of 22 3 5‟ 2‟ 5‟ 1 1” 4” 2” 3” 2 3‟ 7” 7” 6”α 6”β 6‟ O O O N O 22 O O O N O 1' 5' 6' 1 2 3 2' 3' 1'' 2'' 3'' 4'' 5'' 4' 6'' 7'' 22
DSC Thermgraph: 11 DSC Thermgraph: 12 O H N O O N H N Cl 11 O H N O O H N N Cl 12
DSC Thermgraph: 13 DSC Thermgraph: 14 O H N O O N H N Cl 13 14 O H N O O N H N Cl
DSC Thermgraph: 15 DSC Thermgraph: 16 O H N O O N H N Cl 15 16 O N O O H N N Cl
DSC Thermgraph: 17 DSC Thermgraph: 18 O H N O O O O N H N Cl 17 18 O H N O O N H N N Cl
DSC Thermgraph: 19 O O O N N N Cl 19
TGA Thermgraph: 11 TGA Thermgraph: 12 O H N O O N H N Cl 11 O H N O O H N N Cl 12
TGA Thermgraph: 13 TGA Thermgraph: 14 O H N O O N H N Cl 13 14 O H N O O N H N Cl
TGA Thermgraph: 15 TGA Thermgraph: 16 O H N O O N H N Cl 15 16 O N O O H N N Cl
TGA Thermgraph: 17 TGA Thermgraph: 18 O H N O O O O N H N Cl 17 18 O H N O O N H N N Cl
TGA Thermgraph: 19 O O O N N N Cl 19
Addendum B: Analytical data for Chapter 4
_________________________________________________________________________ IR: 10 O HO O O 101H NMR in DMSO: 10 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 ppm 2 .3 3 2 .3 7 2 .4 0 2 .4 9 2 .4 9 2 .4 9 2 .5 0 3 .0 8 3 .1 5 3 .3 7 5 .7 4 6 .4 4 6 .4 4 6 .4 4 6 .4 4 7 .7 0 7 .7 1 7 .7 3 7 .7 4 7 .7 6 7 .7 7 7 .8 0 7 .8 0 7 .8 4 7 .8 9 7 .9 1 7 .9 2 7 .9 3 7 .9 4 7 .9 7 7 .9 8 7 .9 9 8 .0 0 8 .0 1 8 .1 1 1 0 .0 9 1 3 .1 4 1 3 .1 5 1 8 .7 1 5 .3 4 1 .8 2 1 4 .3 5 5 .9 8 1 .0 8 1 0 .4 5 1 .1 6 6 .4 9 1 2 .6 2 1 2 .6 1 5 .5 4 7.70 7.75 7.80 7.85 7.90 7.95 8.00 8.05 ppm 7 .7 0 7 .7 1 7 .7 3 7 .7 4 7 .7 6 7 .7 7 7 .8 0 7 .8 0 7 .8 4 7 .8 9 7 .9 1 7 .9 2 7 .9 3 7 .9 4 7 .9 7 7 .9 8 7 .9 9 8 .0 0 8 .0 1 1 .0 8 1 0 .4 5 1 .1 6 6 .4 9 1 2 .6 2 1 2 .6 1 13 C NMR in DMSO: 10 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 1 3 .7 7 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 0 .0 4 4 8 .6 1 1 0 9 .6 5 1 2 2 .0 3 1 2 4 .1 7 1 2 8 .7 4 1 2 9 .7 4 1 2 9 .9 4 1 3 1 .9 9 1 3 8 .6 6 1 4 0 .7 6 1 5 1 .8 3 1 5 8 .9 8 1 6 6 .8 7 1 7 5 .4 7 O HO O O 1 2 3 1' 2' 3' 4' 5' 6' a 10 1" 2" 2" 3" 3" 4" 5" O HO O O 1 2 3 1' 2' 3' 4' 5' 6' a 10 1" 2" 2" 3" 3" 4" 5" a 4‟ 2” 3” 3‟ 2 1 2 H2O 6‟ 3 5” 2‟ 5‟ 1 1” 4” 2” 3” 2 2 4‟ 6‟ 4‟ 6‟ 3 5” 3” 2” 1 a 2” 3” 4‟ 2‟ 5‟ 4” 1” 3‟
DEPT135 in DMSO: 10 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .7 7 3 9 .3 4 3 9 .4 8 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 0 .0 3 5 9 .3 9 1 0 9 .6 5 1 2 2 .0 4 1 2 4 .1 6 1 2 8 .7 5 1 2 9 .7 4 1 4 0 .7 6 1 5 8 .9 8 COSY in DMSO: 10 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 ppm 13 12 11 10 9 8 7 6 5 4 3 2 1 O HO O O 10 O HO O O 10
HSQC in DMSO: 10 ppm 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 HRMS: 10 O HO O O 10 O HO O O 10
IR: 11 1H NMR in DMSO: 11 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 2 .4 1 2 .5 0 3 .0 4 3 .0 7 4 .0 0 4 .1 3 4 .1 5 4 .1 6 4 .2 1 4 .2 4 4 .4 4 6 .4 6 7 .7 1 7 .7 3 7 .7 5 7 .7 8 7 .8 2 7 .9 5 8 .9 6 9 .0 9 6 .7 5 6 .1 7 5 .2 8 5 .0 3 4 7 .1 6 2 .2 1 1 6 .2 6 6 .3 1 6a OH of EtOH H2O DMSO EtOH NH+ 2” 3” 3‟ 1, 2 4‟ Et2O 3b 2b 6‟ H N N H O O O Fe 11 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N H O O O Fe 2b 3b 1 2 3 2' 3' 4' 5' 6' 1" 2" 3" 4" 5" 11 Et2O 1b 2a 3a 4a
13C NMR in DMSO: 11 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 ppm 1 3 .8 0 1 5 .2 0 3 5 .8 7 3 9 .2 4 3 9 .3 8 3 9 .5 2 3 9 .6 6 3 9 .8 0 4 5 .5 1 4 6 .2 9 6 8 .7 7 6 8 .8 7 7 0 .5 8 7 6 .8 2 1 0 9 .6 5 1 2 2 .0 1 1 2 3 .6 2 1 2 7 .9 6 1 2 8 .6 0 1 3 5 .1 3 1 3 7 .3 4 1 4 0 .9 8 1 5 1 .8 7 1 5 8 .9 6 1 6 3 .3 9 1 6 6 .0 9 1 7 5 .5 5 DEPT135 in DMSO: 11 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 1 3 .8 1 3 5 .8 8 3 9 .2 1 3 9 .3 6 3 9 .3 9 3 9 .5 0 3 9 .6 3 3 9 .6 7 3 9 .7 7 3 9 .9 1 4 0 .0 5 4 5 .5 1 4 6 .2 8 6 4 .9 6 6 8 .7 8 6 8 .8 7 7 0 .5 8 1 0 9 .6 5 1 2 2 .0 3 1 2 3 .6 2 1 2 7 .9 6 1 2 8 .6 0 1 4 0 .9 8 3 5” 2‟ 5‟ 1 1” 4” 2 2” 3” 3‟ 3a 4a 1a 2a 4‟ 1b 2b 1b EtOH 6‟ Et2O 6‟ 3b 2b 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N H O O O Fe 2b 3b 1 2 3 2' 3' 4' 5' 6' 1" 2" 3" 4" 5" 11 ox DMSO H N N H O O O Fe 11
COSY in DMSO: 11 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 HSQC in DMSO: 11 ppm 1 2 3 4 5 6 7 8 9 10 ppm 140 120 100 80 60 40 20 0 H N N H O O O Fe 11 H N N H O O O Fe 11
HRMS: 11 H N N H O O O Fe 11
IR: 12 1H NMR in DMSO: 12 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 1 .8 6 1 .9 0 2 .4 0 2 .4 9 2 .8 8 3 .3 2 3 .3 4 3 .3 6 3 .3 7 3 .3 8 3 .9 4 4 .1 9 4 .2 8 4 .3 9 6 .4 5 7 .7 0 7 .7 3 7 .7 7 7 .8 1 7 .9 3 7 .9 7 8 .8 2 4 .0 5 6 .2 5 4 .0 3 5 .4 9 4 5 .7 7 2 .0 0 1 4 .4 8 5 .0 6 NH+ 3” 2” 2a 1, 2 3‟ 4‟ 4b 6‟ Et2O Fe H N HN O O O 12 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N HN O O O Fe 2b 3b 4b 1 2 3 2' 3' 4' 5' 6' 1" 2" 3" 4" 5" 12 2b DMSO 1b 3a 4a
13C NMR in DMSO: 12 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150 155 160 165 170 175 180 ppm 1 3 .7 9 2 5 .8 3 3 6 .4 4 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 3 .9 1 4 6 .2 4 6 8 .7 5 6 8 .8 2 7 0 .4 7 7 6 .8 8 1 0 9 .6 3 1 2 1 .9 8 1 2 3 .5 3 1 2 7 .7 8 1 2 8 .6 1 1 3 5 .4 4 1 3 7 .1 9 1 4 1 .0 0 1 5 1 .8 5 1 5 8 .9 3 1 6 3 .1 6 1 6 5 .8 6 1 7 5 .5 5 DEPT135 in DMSO: 12 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 ppm 1 3 .7 9 3 6 .4 4 3 9 .1 8 3 9 .3 4 3 9 .3 7 3 9 .4 8 3 9 .5 1 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 0 .0 3 6 8 .7 5 6 8 .8 2 7 0 .4 8 1 0 9 .6 3 1 2 1 .9 8 1 2 3 .5 2 1 2 7 .7 8 1 2 8 .6 1 1 4 1 .0 0 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N HN O O O Fe 2b 3b 4b 1 2 3 2' 3' 4' 5' 6' 1" 2" 3" 4" 5" 12 3 5” ox 2‟ 5‟ 1 1” 4” 2” 2 3‟ 3” 1a 4‟ 2a 3a, 4a 1b 4b 2b 3b 6‟ DMSO Fe H N HN O O O 12
COSY in DMSO: 12 ppm 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 HSQC in DMSO: 12 ppm 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 Fe H N HN O O O 12 Fe H N HN O O O 12
HRMS: 12 Fe H N HN O O O 12
IR: 13 1H NMR in DMSO: 13 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 ppm 1 .5 5 2 .4 0 2 .4 9 2 .8 5 3 .2 7 3 .9 2 4 .1 9 4 .2 2 4 .3 8 4 .8 9 5 .2 6 5 .2 9 5 .3 0 5 .7 4 6 .4 5 7 .7 2 7 .8 0 7 .9 2 7 .9 7 8 .6 5 8 .7 4 8 .7 6 6 .4 2 5 .1 1 6 .4 7 3 .0 7 3 .1 5 2 1 .1 4 2 7 .0 7 2 .3 2 1 1 .8 2 4 .9 1 NH+ 2a 1b 2”, 3” 1, 2 3‟ 5b 2b 4‟ Et2O 3b, 4b 6‟ Et2O Fe H N N H O O O 13 3a 4a amide DMSO 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N H O O O Fe 2b 3b 4b 5b 1 2 3 2' 3' 4' 5' 1" 2" 3" 4" 5" 13 6'
13C NMR in DMSO: 13 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 ppm 1 3 .8 0 1 5 .2 0 2 3 .0 5 2 6 .2 9 3 8 .6 1 3 9 .0 8 3 9 .2 2 3 9 .3 6 3 9 .5 0 3 9 .6 4 3 9 .7 8 3 9 .9 2 4 5 .8 2 4 6 .3 2 6 4 .9 5 6 8 .7 7 6 8 .8 7 7 0 .4 7 7 6 .9 2 1 0 9 .6 4 1 2 1 .9 7 1 2 3 .4 7 1 2 7 .7 5 1 2 8 .6 2 1 3 5 .7 7 1 3 7 .0 8 1 4 1 .0 6 1 5 1 .8 7 1 5 8 .9 4 1 6 2 .1 4 1 6 5 .6 0 1 7 5 .5 8 DEPT135 in DMSO: 13 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 ppm 1 3 .8 0 1 5 .2 0 2 6 .3 0 3 8 .6 1 3 9 .2 1 3 9 .3 4 3 9 .3 7 3 9 .4 8 3 9 .5 2 3 9 .6 1 3 9 .7 5 3 9 .8 9 4 0 .0 3 6 4 .9 5 6 8 .7 7 6 8 .8 7 7 0 .4 7 1 0 9 .6 4 1 2 1 .9 8 1 2 3 .4 6 1 2 7 .7 5 1 2 8 .6 2 1 4 1 .0 5 3 5” 2‟ 5‟ ox 1 1a 1” 4” 2a 2” 3” 2 3‟ 4‟ Et2O 1b, 5b 2b 4b 3b 6‟ 3a, 4a Et2O DMSO Fe H N N H O O O 13 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N H O O O Fe 2b 3b 4b 5b 1 2 3 2' 3' 4' 5' 1" 2" 3" 4" 5" 13 6'
COSY in DMSO: 13 ppm -0.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 10 9 8 7 6 5 4 3 2 1 0 HSQC in DMSO: 13 ppm 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 Fe H N N H O O O 13 Fe H N N H O O O 13
HRMS: 13 Fe H N N H O O O 13
IR: 14 1H NMR in DMSO: 14 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 1 .0 8 1 .1 4 1 .1 6 1 .1 7 1 .2 1 2 .4 0 2 .4 9 2 .6 0 2 .9 8 3 .3 5 3 .3 6 3 .3 7 3 .3 8 3 .6 4 3 .9 7 3 .9 9 4 .0 1 4 .0 2 4 .2 0 4 .2 4 4 .4 2 4 .7 1 4 .7 3 6 .4 5 7 .4 5 7 .7 1 7 .7 9 7 .9 0 2 2 .9 2 3 .6 4 4 .6 5 4 .4 0 4 4 .8 1 1 .6 4 3 .0 9 3 .2 6 1 .7 0 3 .1 7 4a NH+ 2” 1, 2 3” 3‟ 4‟ 3a H2O 2a 1b 6‟ Et2O Fe H N N N O O O 14 4" 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N N O O O Fe 2b 3b 4b 5b 1 2 3 2' 3' 4' 5' 1" 2" 3" 5" 14 2b-5b DMSO
13C NMR in DMSO: 14 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 ppm 1 3 .7 8 4 2 .3 4 4 6 .3 5 5 2 .7 8 6 8 .7 7 6 8 .8 9 7 0 .5 1 7 6 .9 6 1 0 9 .6 3 1 2 1 .8 7 1 2 3 .1 3 1 2 7 .5 4 1 2 8 .7 4 1 3 5 .6 5 1 3 7 .3 5 1 4 1 .1 7 1 5 1 .8 6 1 5 8 .8 9 1 6 2 .5 2 1 6 8 .3 7 1 7 5 .6 1 DEPT135 in DMSO: 14 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 1 3 .7 8 3 9 .2 0 3 9 .3 4 3 9 .3 7 3 9 .4 8 3 9 .6 1 3 9 .6 5 3 9 .7 5 3 9 .7 9 3 9 .8 9 4 0 .0 3 6 8 .7 7 6 8 .8 9 7 0 .5 1 1 0 9 .6 3 1 2 1 .8 7 1 2 3 .1 3 1 2 7 .5 4 1 2 8 .7 4 1 4 1 .1 7 3 .3 0 2 8 .1 0 2 8 .4 3 4 .5 2 4 .6 5 3 .3 7 4 .5 7 7 .5 2 8 .6 1 1 .6 6 5 .2 7 3 5” 2‟ 5‟ 2a ox 1a 1 1” 4” 2” 3” 3‟ 2 4‟ 3a, 4a 5b 1b 6‟ 4" 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N N O O O Fe 2b 3b 4b 5b 1 2 3 2' 3' 4' 5' 1" 2" 3" 5" 14 DMSO Fe H N N N O O O 14
COSY in DMSO: 14 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 ppm 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 HSQC in DMSO: 14 ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 ppm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 Fe H N N N O O O 14 Fe H N N N O O O 14
HRMS: 14 Fe H N N N O O O 14
IR: 15 1H NMR in DMSO: 15 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ppm 1 .0 6 1 .0 7 1 .0 8 1 .1 9 1 .2 1 2 .3 3 2 .4 0 2 .4 9 2 .9 9 3 .0 6 3 .0 8 3 .3 4 3 .3 6 3 .3 7 3 .3 8 3 .5 5 4 .0 5 4 .1 9 4 .2 2 4 .2 9 4 .4 0 6 .4 5 7 .7 2 7 .7 8 7 .8 1 7 .9 4 7 .9 5 7 .9 7 8 .6 4 8 .7 5 8 .8 1 8 .8 9 8 .9 5 7 .9 8 7 .7 2 6 .1 7 7 .6 5 4 4 .6 6 2 .5 4 1 6 .7 3 4 .0 3 NH+ 3b, 2a 2” 3” 3‟ 1 2 4‟ Et2O 3a 4a 6‟ 4b H N N H O O O Fe 15 4a 4a 4a 4a 4a 3a 2a 3a 2a 1a 1b H N N H O O O Fe 2b3b 4b 1 2 3 2' 3' 4' 5' 6' 1" 2" 3" 4" 5" 15 Et2O DMSO
