Syntheses of 5,8-Disubstituted Indolizidine Poison-frog Alkaloids

doi:10.3969/j.issn.0251-0790.2012.03.015

Abstract

Abstract:

A diverse array of biologically active alkaloids has been detected in amphibian skin, which contains over 20 structural classes and more than 800 alkaloids. Most of these alkaloids appear to be derived from dietary sources such as ants, beetles, mites and so on. A great number of the alkaloids show very interesting biological activities such as pharmacological effects at neuronal nicotinic acetylcholine receptors. However, these alkaloids have been isolated in minute amounts from the amphibian skin. Consequently, a great need for the development of the synthetic strategy of these alkaloids has arisen for the determination of the structures of natural products and the investigations of their biological activities. The 5,8-disubstituted indolizidines constitute the largest subclass of alkaloids, and about 80 alkaloids have been detected up to present. In this paper, we report the syntheses of the analogous indolizidines (-)-203A, (-)-209B, (-)-235B″, (-)-231C, (-)-233D, (-)-219F, (-)-221I, (-)-193E(Proposed), (-)-251N and 221K(Proposed) using the stereoselective Michael conjugate addition reaction as the key step. Furthermore, the absolute stereochemistry of (-)-203A and (-)-233D was established, and the relative stereochemistry of 231C, 219F, 221I and 251N was established.

Key words: Michael conjugate addition, Poison-frog alkaloid, Total synthesis, Absolute stereochemistry, Relative stereochemistry

CLC Number:

O629.39

TrendMD:

ZHOU De-Jun, TOYOOKA Naoki. Syntheses of 5,8-Disubstituted Indolizidine Poison-frog Alkaloids[J]. Chem. J. Chinese Universities, 2012, 33(03): 511.

References

[1] Daly J. W., Spande T. F., Garraffo H. M.. J. Nat. Prod.[J], 2005, 68: 1556-1575
[2] Daly J. W.. J. Med. Chem.[J], 2003, 46: 445-452
[3] Daly J. W., Garraffo H. M., Spande T. F.; Ed.: Pelletier S. W.. Alkaloids: Chemical and Biological Perspectives[M], New York: Pergamon Press, 1999, 13: 1-161
[4] Daly J. W.; Ed.: Cordell G. A.. The Alkaloids[M], New York: Academic Press, 1998, 50: 141-169
[5] Daly J. W., Kaneko T., Wilham J., Garraffo H. M., Spande T. F., Espinosa A., Donelly M.. Proc. Natl. Acad. USA[J], 2002, 99: 13996-14001
[6] Clark V. C., Raxworthy C. J., Rakotomalala V., Sierwald P., Fisher B. L.. Proc. Natl. Acad. USA[J], 2005, 102: 11617-11622
[7] Hodgkinson T. J., Shipman M.. Synthesis[J], 1998: 1141-1144
[8] Comins D. L., Dehghani A.. Tetrahedron Lett.[J], 1992, 33: 6299-6302
[9] Cacchi S., Morera E., Orter G.. Tetrahedron Lett.[J], 1985, 26: 1109-1112
[10] Toyooka N., Nemoto H.. Recent Res. Dev. Org. Chem.[J], 2002, 6: 611-624
[11] Basha A., Lipton M., Weinreb S. M.. Tetrahedron Lett.[J], 1977, 18: 4171-4174
[12] Dess D. B., Martin J. C.. J. Org. Chem.[J], 1983, 48: 4155-4156
[13] Dess D. B., Martin J. C.. J. Am. Chem. Soc.[J], 1991, 113: 7277-7287
[14] Ireland R. E., Lin L.. J. Org. Chem.[J], 1993, 58: 2899
[15] Stork G., Zhao K.. Tetrahedron Lett.[J], 1989, 30: 2173-2174
[16] XU Bo-Yan(许柏岩), SONG Na(宋娜), LI Wen-Ze(李文泽), XIN Zhi-Jun(辛志军), LI Ying(李瀛). Chem. J. Chinese Universities(高等学校化学学报)[J], 2009, 30(7): 1329-1331
[17] Takahashi S., Kuroyama Y., Sonogashira K., Hagihara N.. Synthesis[J], 1980: 627-630
[18] Toyooka N., Zhou D. J., Nemoto H., Garraffo H. M., Spande T. F., Daly J. W.. Tetrahedron Lett.[J], 2006, 47: 577-580
[19] Tamao K., Sumitani K., Kumada M.. J. Am. Chem. Soc.[J], 1972, 94: 4374-4376
[20] Comins D. L., LaMunyon D. H., Chen X.. J. Org. Chem.[J], 1997, 62: 8182-8187
[21] Shishido Y., Kibayashi C.. J. Org. Chem.[J], 1992, 57: 2876-2883
[22] Seyferth D., Marmor R. S., Hilbert P.. J. Org. Chem.[J], 1971, 36: 1379-1385
[23] Toyooka N., Zhou D. J., Nemoto H., Garraffo H. M., Spande T. F., Daly J. W.. Tetrahedron Lett.[J], 2006, 47: 581-582
[24] Toyooka N., Zhou D. J., Nemoto H., Garraffo H. M., Spande T. F., Daly J. W.. Heterocycles[J], 2006, 70: 541-548
[25] Hoffmann R. W.. Chem. Rev.[J], 1989, 89: 1841-1860
[26] Deslongchamps P.. Stereoelectronic Effects in Organic Chemistry[M], New York: Pergamon, 1983: 203-290