Nucleophilic Opening of N-Carboalkoxy-2,3-anhydro-1-deoxymannojirimycin. A Useful Method for the Syntheses of 2-, 3- and 2,3-Disubstituted 1-Deoxynojirimycin Analogs |
| |
Authors: | Ish K. Khanna Francis J. Koszyk Michael A. Stealey Richard M. Weier Janet Julien Richard A. Mueller |
| |
Affiliation: | Departments of Chemistry and Physical Methodology , G. D. Searle and Co. , 4901 Searle Parkway, Skokie, IL, 60077 |
| |
Abstract: | Abstract A useful methodology for the synthesis of a number of 2-, 3- and 2,3-disubstituted deoxynojirimycin analogs is reported. It has been found that the epoxides in stereoselectively synthesized N-carboalkoxy-2,3-anhydro-1-deoxymannojirimycins (4 and 5) react with N-, S- and F- nucleophiles to give a mixture of gluco and altro products. The 3-azido altro compound (12b) yields the desired gluco derivative (40) by oxidation, in situ epimerization at C-3, followed by stereoselective reduction of the carbonyl group. The azido intermediate (12a) affords the 2,3-diazido gluco compound (51) by double inversion at C-3. Attempts have been made to understand the factors contributing to the opening of epoxides (4, 5 and 9) by different nucleophiles. |
| |
Keywords: | |
|
|