6,6,6-三氟-L-柔红糖胺和6,6,6-三氟-L-阿可糖胺的立体选择性合成。

A stereoselective synthesis of 6,6,6-trifluoro-L-daunosamine and 6,6,6-trifluoro-L-acosamine.

作者信息

Hayman Colin M, Larsen David S, Simpson Jim, Bailey Karl B, Gill Gurmit Singh

机构信息

Department of Chemistry, University of Otago, P.O. Box 56, Dunedin, New Zealand.

出版信息

Org Biomol Chem. 2006 Jul 21;4(14):2794-800. doi: 10.1039/b606055b. Epub 2006 Jun 21.

DOI:10.1039/b606055b

PMID:16826305

Abstract

A short synthesis of 6,6,6-trifluoro-L-acosamine 15 and 6,6,6-trifluoro-L-daunosamine 19 has been accomplished. The pyranose ring system of these carbohydrate analogues was formed by a hetero-Diels-Alder reaction of vinylogous imide 11 and ethyl vinyl ether which gave adduct 12a in 40% yield. Hydroboration gave 13 and subsequent hydrogenolytic removal of the (R)-2-phenylethyl chiral auxiliary gave ethyl 6,6,6-trifluoro-L-acosaminide 14. Acid hydrolysis furnished target 15. Glycoside 13 was N-trifluoroacetylated to give 16, the structure was confirmed by single crystal X-ray diffraction. The C-4 stereochemistry of 16 was inverted by Swern oxidation of the 4-OH group, and subsequent borohydride reduction to give 17. Hydrogenolytic removal of the auxiliary gave ethyl-6,6,6-trifluoro-L-daunosaminide 18. Acid hydrolysis provided 19.

摘要

已完成6,6,6-三氟-L-阿考胺15和6,6,6-三氟-L-柔红糖胺19的简短合成。这些碳水化合物类似物的吡喃糖环系统是通过烯醇式酰亚胺11与乙烯基乙醚的杂环狄尔斯-阿尔德反应形成的，该反应以40%的产率得到加合物12a。硼氢化反应得到13，随后通过氢解去除(R)-2-苯乙基手性助剂得到6,6,6-三氟-L-阿考胺乙酯14。酸水解得到目标产物15。糖苷13经N-三氟乙酰化得到16，其结构通过单晶X射线衍射得以确认。通过对4-OH基团进行斯文氧化，然后用硼氢化物还原，使16的C-4立体化学发生反转，得到17。通过氢解去除助剂得到6,6,6-三氟-L-柔红糖胺乙酯18。酸水解得到19。