Asymmetric total synthesis of 5′-epi-paecilomycin-F

The asymmetric total synthesis of one of the stereoisomers of the naturally occurring 14-membered ring macrolide paecilomycin-F (5′-epi) has been reported in this article. The main highlight of the synthetic strategy involves the successful application of a ring closing metathesis (RCM) reaction at a late stage. Asymmetric Keck allylation, Sharpless asymmetric dihydroxylation, and Mitsunobu esterification have also been used successfully for the total synthesis of 5′-epi-paecilomycin-F.

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(R)-6-(4-Methoxybenzyloxy)hexan-2-yl acetateC16H24O4[α]D30=-1.9 (c 2.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(R)-6-(4-Methoxybenzyloxy)hexan-2-olC14H22O3[α]D30=+7.6 (c 2.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

((R)-6-(4-Methoxybenzyloxy)hexan-2-yloxy)(tert-butyl)diphenylsilaneC30H40O3Si[α]D30=+8.4 (c 1.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(R)-5-tert-Butyldiphenylsilyloxy-hexan-1-olC22H32O2Si[α]D30=+4.6 (c 1.3, MeOH).Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(R)-5-tert-butyldiphenylsilanyloxy-hexanalC22H30O2Si[α]D30=+8.2 (c 1.6, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(R,E)-ethyl 7-tert-butyldiphenylsilanyloxy-oct-2-enoateC26H36O3Si[α]D30=+11.5 (c 2.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(2S,3R,7R)-Ethyl 2,3-dihydroxy-7-tert-butyldiphenylsilanyloxy-octanoateC26H38O5Si[α]D30=+13.2 (c 1.6, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S,3R,7R)

(4S,5R)-Ethyl-5-((R)-4-tert-butyldiphenylsilanyloxy-pentyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylateC29H42O5Si[α]D30=+13.0 (c 1.7, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S,3R,7R)

(4S,5R)-5-((R)-4-tert-Butyldiphenylsilanyloxy-pentyl)-2,2-dimethyl-1,3-dioxolane-4-carbaldehydeC27H38O4Si[α]D30=+5.2 (c 1.2, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,R)

(S)-1-((4R,5R)-5-((R)-4-tert-Butyldiphenylsilanyloxy-pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-3-en-1-olC30H44O4Si[α]D30=17.5 (c 1.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,R,R)

((R)-5-((4R,5R)-5-((S)-1-(Methoxymethoxy)but-3-enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pentan-2-yloxy)(tert-butyl)diphenylsilaneC32H48O5Si[α]D30=+28.3 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,R,R)

(R)-5-((4R,5R)-5-((S)-1-(Methoxymethoxy)but-3-enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pentan-2-olC16H30O5[α]D30=+8.3 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (R,R,R,S)

(S)-5-((4R,5R)-5-((S)-1-(Methoxymethoxy)but-3-enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pentan-2-yl 2-hydroxy-4-methoxy-6-vinylbenzoateC26H38O8[α]D30=+42.1 (c 0.6, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,R,S)

(S)-5-((4R,5R)-5-((S)-1-(Methoxymethoxy)but-3-enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pentan-2-yl 2-hydroxy-4-methoxy-6-vinylbenzoateC25H36O7[α]D30=+52.7 (c 0.7, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S,R,R,S)

(E,7S,11R,12S,13S)-7,8,9,10,11,12,13,14-octahydro-4,11,12,13-tetrahydroxy-2-methoxy-7-methylbenzo[14]annulen-5(6H)-oneC20H28O6[α]D30=+30.7 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (7S,11R,12S,13S)