The asymmetric syntheses of methyl D-digitoxoside, L-oleandrose and L-cymarose from methyl sorbate, an achiral precursor

Article abstract of DOI:10.1248/cpb.c12-00308

The addition of 4 eq of chloral to osmundalactone (4S,5R)-4 gave quantitative formation of the hemiacetal derivative (4S,5R)-8, which was treated with methane sulfonic acid to afford the intramolecular Micheal addition product (+)-(3S,4S,5R)-9 possessing a 3,4-cis-dihydroxy-d-lactone in 78% overall yield from (4S,5R)-4. The obtained (+)-(3S,4S,5R)-9 was subsequently converted to methyl D-digitoxoside (pyranoside) (12) in 13% overall yield and methyl D-digitoxoside (furanoside) (12) in 20% overall yield. The reaction of benzyl-osmundalactone (4R,5S)-3 and MeOH in the presence of Amberlyst A-26 as a basic catalyst gave 3,4-trans-δ-lactone (-)-(3S,4R,5S)-20 in 28% yield and 3,4-cis-d-lactone (-)-(3R,4R,5S)-21 in 45% yield. Dibal-H reduction of (-)-(3S,4R,5S)-20 followed by catalytic hydrogenation gave L-oleandrose (6) in 86% overall yield, while Dibal-H reduction of (-)-(3R,4R,5S)-21 followed by catalytic hydrogenation provided L-cymarose (7) in 85% overall yield.