Synthesis of conduritol epoxides and aziridines and methods of u

Details Synthesis of conduritol epoxides and aziridines and methods of u Synthesis of conduritol epoxides and aziridines and methods of u

1997-02-11

1998-11-10

Kight, John

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 168, 536124, 548961, 568811, 568822, 568832, C07D20326, C07H 1704, C07H 1100, C07G 1700

Patent

active

058346066

DESCRIPTION:

BRIEF SUMMARY
This patent application claims priority to U.S. Ser. No. 08/261,586 filed Jun. 17, 1994, under 35 U.S.C. .sctn.120.


FIELD OF THE INVENTION

This invention relates to novel processes for the synthesis of certain conduritol epoxides and aziridines and the use of these epoxides and aziridines to synthesize various or higher disaccharides such as conjugates of cyclitols and/or carbohydrates and their carbocyclic analogs (C-analogs), as well as various heteroatom-linked conjugates such as N-, S- or O-linked conjugates. This invention also relates to certain novel compounds useful as synthons and/or as therapeutic agents useful in treating various disease in a mammal.


BACKGROUND OF THE INVENTION

The expression of arene cis-diols was originally discovered and described by Gibson 24 years ago (Gibson, D. T.; Hensley, M.; Yoshioka, H.; Mabry, J. J. Biochemistry, 1970, 9, 1626). Since that time, use of such arene cis-diols in enantiocontrolled synthesis of oxygenated compounds has gained increasing acceptance by those skilled in the art. Many examples of their applications to the total synthesis of carbohydrates, cyclitols, and oxygenated alkaloids can be found in the literature; however, much of the work done within this area has been with the more traditional approach of attaining optically pure compounds from the carbohydrate chiral pool. (Hanessian, S. in Total Synthesis of Natural Products: The Chiron Approach; Pergamon: Oxford, 1983).
The synthesis of glycoconjugates has attracted considerable attention conference, San Francisco, 1993!. Higher saccharides such as the gangliosides GM3 and sialyl Lewis x both of which are proposed to be involved in malignancy and intercellular adhesion, trans-cell membrane signal transduction and regulation of cell growth have been the subject of Ruggeri, R. B. Science 1993, 260, 1307; (b) Liu, K. K. -C.; Danishefsky, S. J. J. Am. Chem. Soc. 1993, 115, 4933! by chemical as well as enzymatic Garcia-Junceda, E.; Williams, M. A.; Bayer, R.; Ketcham, C.; Walker, L. E.; Paulson, J. C.; Wong, C. -H. Am. Chem. Soc. 1992, 114, 9283!. The current chemical and/or enzymatic synthesis of these compounds is arduous at best giving rise to a growing body of high yielding, selective, Kahne, D. A one-step synthesis of the ciclamycin trisaccharide. J. Am. Chem. Soc., 1993, 115, 1580 and the references therein.; (b) Frazer-Reid, B.; Zugan, W.; Andrews, W.; Skowronski, E. Torsional effects in glycoside reactivity: saccharide couplings mediated by acetate protecting groups. J. Am. Chem. Soc., 1991, 513, 1434.; (c) Frazer-Reid, B. n-Pentenyl glycosides in organic chemistry: a contemporary example of serendipity. Synlett, 1992, 927.; (d) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. An efficient thioglycoside-mediated formation of .alpha.-glycosidic linkages promoted by iodonium dicollidine perchlorate. Tetrahedron Lett., 1990, 31, 274.; (e) Kondo, H.; Achi, S.; Ichikawa, Y.; Halcomb, R. C.; Ritzen, H.; Wong, C. -H. Glycosyl phosphites as glycosidation reagents: scope and mechanism. J. Org. Chem., 1994, 59, 864.; (f) Toshima, K.; Nozaki, Y.; Inokuchi, H.; Nakata, M.; Tatsuta, K.; Kinoshita, M. A new entry for the controlled synthesis of 2,6-dideoxy oligosaccharides. Tetrahedron Lett., 1993, 34, 1611!. However, these glycosidation methods are incompatible if the glycosidic donor is to be a carba-sugar and, therefore, would not be useful if a fully carbocyclic oligosaccharide analog were required. Thus, the carbocyclic analogs of these types of compounds are generally unattainable by currently available methods, generally: Hanessian supra!.
Whereas the carbocyclic analogs of simple sugars are known (Suami, T.; Ogawa, S. In Advances in Carbohydrate Chemistry and Biochemistry; Tipson, R. S.; Horton, D., Eds.; Academic: New York, 1990; Vol. 48, p 21; Ley, S. V.; Yeung, L. L. Synlett 1992, 291) an attempt at rational and exhaustive design of higher members is absent in the literature.
The present invention alleviates the problems associated with prior chemical or enzymatic synthesis for making c

REFERENCES:
Zipperer et al, Chem. Ber., vol. 171, (1988), pp. 757-780.
Ley et al, SYNLETT (1992) pp. 291-292 "Microbial Oxidation in Synthesis: Preparation of Pseudo-alpha-D-glucopyranose from Benzene".
Paulsen et al, Chemical Abstract, vol. 112, No. 139199, (1990) "Cyclit Reactions".

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