Divergent syntheses of all 16 carbasugar stereoisomers via stereoconversion of carba-β-d-altropyranose derivatives

We have developed practical synthetic routes to enantiopure d- and l-carba-β-altrose derivatives and all the possible stereoisomers via their divergent stereoconversions. Carba-β-d-altrose was prepared from 3-cyclohexene-1-carboxylic acid and converted to carba-β-d-mannose, carba-β-d-idose, and carba-β-d-talose derivatives via regio- and stereoselective oxidation/reduction of 3-OH and/or 4-OH. The four carbasugar stereoisomers were then transformed to the remaining 12 carbasugar stereoisomers and their 1,2-epoxides by regio- and stereoselective manipulation of hydroxyl groups in C1 and C2, which includes oxidation/reduction, Mitsunobu’s reaction, olefination/dihydroxylation, and epoxidation/ring-opening protocols.

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1-O-Benzoyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-β-d-allopyranoseC44H48O6Side = 90%[α]D22=-6.0(c0.45,CHCl3)Source of chirality: enzymatic resolution

2-O-Benzoyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-altropyranoseC44H48O6Side >99%[α]D19=-13.7(c1.48,CHCl3)Source of chirality: enzymatic resolution

3,4-Di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-1-O-methoxymethyl-5a-carba-α-d-allopyranoseC39H48O6Side >99%[α]D22=+16.7(c0.50,CHCl3)Source of chirality: enzymatic resolution

2-O-Benzoyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-β-d-glucopyranoseC44H48O6Side >99%[α]D21=+47.9(c0.76,CHCl3)Source of chirality: enzymatic resolution

3,4-Di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-glucopyranoseC37H44O5Side >99%[α]D21=+37.8(c1.43,CHCl3)Source of chirality: enzymatic resolution

3,4-Di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-mannopyranoseC37H44O5Side >99%[α]D21=+3.0(c0.44,CHCl3)Source of chirality: enzymatic resolution

1-O-Allyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-idopyranoseC40H48O5Side >99%[α]D20=+19.3(c1.05,CHCl3)Source of chirality: enzymatic resolution

1-O-Allyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-gulopyranoseC40H48O5Side >99%[α]D19=+17.2(c0.53,CHCl3)Source of chirality: enzymatic resolution

1-O-Benzoyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-β-d-gulopyranoseC44H48O6Side >99%[α]D20=-42.7(c0.97,CHCl3)Source of chirality: enzymatic resolution

1-O-Allyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-talopyranoseC40H48O5Side >99%[α]D21=+3.2(c0.80,CHCl3)Source of chirality: enzymatic resolution

3,4-Di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-α-d-galactopyranoseC37H44O5Side >99%[α]D18=+46.9(c1.0,CHCl3)Source of chirality: enzymatic resolution

1-O-Allyl-3,4-di-O-benzyl-6-O-(tert-butyldiphenyl)silyl-5a-carba-β-d-galactopyranoseC40H48O5Side >99%[α]D21=-1.4(c0.58,CHCl3)Source of chirality: enzymatic resolution