Intermediates for incorporation of tetrahydroxypipecolic acid analogues of alpha- and beta-D-mannopyranose into combinatorial libraries: unexpected nanomolar-range hexosaminidase inhibitors. Synthesis of alpha- and beta-homomannojirimycin
Homoazasugars have the distinction as a class of natural products in that most of them have been synthesised before they were isolated. Syntheses of α-1 and β-homomannojirimycin 2 rely on the stereoselective and chemoselective sodium cyanoborohydride reduction of a [2.2.2] bicyclic imino lactone (6)...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1998
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| Summary: | Homoazasugars have the distinction as a class of natural products in that most of them have been synthesised before they were isolated. Syntheses of α-1 and β-homomannojirimycin 2 rely on the stereoselective and chemoselective sodium cyanoborohydride reduction of a [2.2.2] bicyclic imino lactone (6) to give a single [2.2.2] bicyclic amino-lactone (7). Methanolysis of 7 under basic conditions is accompanied by efficient epimerisation of the first formed α-amino-ester (8) to the more stable β-amino-ester (9) in which the 2,6-substitutents are equatorial. Both 7 and 9 are suitable intermediates for the incorporation of tetrahydroxypipecolic acid derivatives into combinatorial libraries containing α- and β-C-glycosyl analogues of aza-D-mannopyranose, respectively. Methylamides derived from 7 and 9 are shown to be specific and potent inhibitors of two β-N-acetylglucosaminidases but have no effect on an α-N-acetylgalactosaminidase. The synthesis of α- 14 and β-17 manno-pipecolic acids is also reported. |
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