A stereoselective synthesis of 6,6,6-trifluoro-L-daunosamine and 6,6,6-trifluoro-L-acosamine.
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.
Hayman
Colin M
CM
Department of Chemistry, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Larsen
David S
DS
Simpson
Jim
J
Bailey
Karl B
KB
Gill
Gurmit Singh
GS
D005461:Fluorine / Q000737:chemistry*; D006595:Hexosamines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D006595:Hexosamines; C007217:daunosamine; D005461:Fluorine; C010669:acosamine