Chemo-enzymatic asymmetric total synthesis of stagonolide-C

The naturally occurring phytotoxic noneolide stagonolide-C has been synthesized by a chemo-enzymatic approach. Two key intermediates have been synthesized by applying a metal–enzyme combined DKR (dynamic kinetic resolution) strategy, followed by RCM (ring-closing metathesis) to afford the target compound in an efficient way.

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Acetic acid (S)-4-(tert-butyl-dimethyl-silanyloxy)-1-vinyl-butyl esterC14H28O3SiEe = 99%[α]D29=-2.7 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (1S)

(S)-6-(tert-Butyl-dimethyl-silanyloxy)-hex-1-en-3-olC12H26O2SiEe = 99%[α]D29=-32.85 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3S)

tert-Butyl-[(S)-4-(4-methoxy-benzyloxy)-hex-5-enyloxy]-dimethyl-silaneC20H34O3SiEe = 99%[α]D29=-18.5 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (4S)

(S)-4-(4-Methoxy-benzyloxy)-hex-5-en-1-olC14H20O3Ee = 99%[α]D29=-20.2 (c 1.75, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (4S)

(S)-4-(4-Methoxy-benzyloxy)-hex-5-enoic acidC14H18O4Ee = 99%[α]D29=-19.9 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (4S)

Acetic acid (R)-3-(4-methoxy-benzyloxy)-1-methyl-propyl esterC14H20O4Ee = 98%[α]D29=-6.45 (c 3.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3R)

(R)-4-(4-Methoxy-benzyloxy)-butan-2-olC12H18O3Ee = 98%[α]D29=-24.4 (c 0.5, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2R)

tert-Butyl-[(R)-3-(4-methoxy-benzyloxy)-1-methyl-propoxy]-diphenyl-silaneC28H36O3SiEe = 98%[α]D29=-22.1 (c 1.2, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3R)

(R)-3-(tert-Butyl-diphenyl-silanyloxy)-butan-1-olC20H28O2SiEe = 98%[α]D29=-2.6 (c 2.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3R)

(R)-3-(tert-Butyl-diphenyl-silanyloxy)-butyraldehydeC20H26O2SiEe = 98%[α]D29=-1.6 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3R)

(3S,5R)-5-(tert-Butyl-diphenyl-silanyloxy)-hex-1-en-3-olC22H30O2Si[α]D29=+1.4 (c 2.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,5R)

tert-Butyl-[(1R,3S)-3-(4-methoxy-benzyloxy)-1-methyl-pent-4-enyloxy]-diphenyl-silaneC30H38O3Si[α]D29=+1.0 (c 1.25, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,3S)

(2R,4S)-4-(4-Methoxy-benzyloxy)-hex-5-en-2-olC14H20O3[α]D29=-13.7 (c 1.25, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S)

(S)-4-(4-Methoxy-benzyloxy)-hex-5-enoic acid (1R,3S)-3-(4-methoxy-benzyloxy)-1-methyl-pent-4-enyl esterC28H36O6[α]D29=-58.3 (c 1.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,S)

(S)-4-Hydroxy-hex-5-enoic acid (1R,3S)-3-hydroxy-1-methyl-pent-4-enylesterC12H20O4[α]D29=-29.3 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,S)

(E)-(5S,8S,10R)-5,8-Dihydroxy-10-methyl-3,4,5,8,9,10-hexahydro-oxecin-2-oneC10H16O4[α]D29=+44.4 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (5S,8S,10R)