314
2
General Synthetic Methods
⊡ Scheme 17
⊡ Scheme 18
In the synthesis of a miharamycin sugar moiety [31], a C-3-branched hexopyranoside was constructed through Wittig reaction and dihydroxylation. Olefination of the ketosugar 47 was performed with [(ethoxycarbonyl)-methylene]triphenylphosphorane affording 48 as a mixture of
isomers (Z:E = 7:3). Oxidation of 48 with OsO 4 in pyridine led to a mixture of stereoisomers 49
in a quantitative yield, whereas a catalytic amount of OsO 4 and 4-methylmorpholine N-oxide
in acetone/water gave only a 66% yield of 49. Similarly, ketone sugar 50 was converted into the
exo-methylene derivative by reaction with H 2 C=CHPPh 3 , a further Sharpless dihydroxylation
using AD-mix (ether α or β) afforded the single stereoisomer [32] ( > Scheme 17).
Asymmetric synthesis of macrolide antibiotic, ossamycin, was started from known 52, which
was further converted into furanoside 53 via zinc reduction and subsequent cyclization
( > Scheme 18). Compound 53 was subjected to hydroboration, Swern oxidation, Wittig
olefination, and hydrogenation furnished key intermediate 55 towards ossamycin [33].
Treatment of 5-O-TBS-1,2-O-isopropylidene-α-D-erythro-pentofuranos-3-ulose 56 with
[(ethoxycarbonyl)-methylene]triphenylphosphorane gave (E/Z)-57 (7:1; 90%) ( > Scheme 19).
Desilylation and hydrogenation of 57 at 25 psi H 2 /Pd-C gave 58 with a trace amount of the
over-reduced diol 59. Formation of 59 was minimized at lower hydrogen pressure (5 psi).
Reduction of 57 with NaBH 4 /EtOH gave worse results. The 1,2-O-isopropylidene group is
known to direct incoming reagents from the β-face of furanosyl derivatives and thus ribo
diastereomers 58 (or 59) were obtained with either catalytic hydrogenation or chemical
reduction [34].
2
General Synthetic Methods
⊡ Scheme 17
⊡ Scheme 18
In the synthesis of a miharamycin sugar moiety [31], a C-3-branched hexopyranoside was constructed through Wittig reaction and dihydroxylation. Olefination of the ketosugar 47 was performed with [(ethoxycarbonyl)-methylene]triphenylphosphorane affording 48 as a mixture of
isomers (Z:E = 7:3). Oxidation of 48 with OsO 4 in pyridine led to a mixture of stereoisomers 49
in a quantitative yield, whereas a catalytic amount of OsO 4 and 4-methylmorpholine N-oxide
in acetone/water gave only a 66% yield of 49. Similarly, ketone sugar 50 was converted into the
exo-methylene derivative by reaction with H 2 C=CHPPh 3 , a further Sharpless dihydroxylation
using AD-mix (ether α or β) afforded the single stereoisomer [32] ( > Scheme 17).
Asymmetric synthesis of macrolide antibiotic, ossamycin, was started from known 52, which
was further converted into furanoside 53 via zinc reduction and subsequent cyclization
( > Scheme 18). Compound 53 was subjected to hydroboration, Swern oxidation, Wittig
olefination, and hydrogenation furnished key intermediate 55 towards ossamycin [33].
Treatment of 5-O-TBS-1,2-O-isopropylidene-α-D-erythro-pentofuranos-3-ulose 56 with
[(ethoxycarbonyl)-methylene]triphenylphosphorane gave (E/Z)-57 (7:1; 90%) ( > Scheme 19).
Desilylation and hydrogenation of 57 at 25 psi H 2 /Pd-C gave 58 with a trace amount of the
over-reduced diol 59. Formation of 59 was minimized at lower hydrogen pressure (5 psi).
Reduction of 57 with NaBH 4 /EtOH gave worse results. The 1,2-O-isopropylidene group is
known to direct incoming reagents from the β-face of furanosyl derivatives and thus ribo
diastereomers 58 (or 59) were obtained with either catalytic hydrogenation or chemical
reduction [34].