Synthetic studies on cytotoxic macrolides cruentarens A and B: stereoselective synthesis of the C8–C19 segment of cruentarens A and B

A stereoselective synthesis of the C8–C19 segment of cruentarens A and B, cytotoxic natural products, has been accomplished. The key steps involve a stereoselective radical cyclization, stereospecific methylation of a γ, δ-epoxy acrylate, nucleophilic epoxide ring opening and a cis-Wittig olefination.

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(3S,4S)-5-(Benzyloxy)-3-methylpentane-1,4-diolC13H20O3[α]D25=+2.2 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (3S,4S)

(2S,3S)-1-(Benzyloxy)-5-(tert-butyldimethylsilyloxy)-3-methylpentan-2-olC19H34O3Si[α]D25=+1.0 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2S,3S)

(5S,6S)-5-(Benzyloxymethyl)-2,2,6,10,10,11,11-heptamethyl-3,3-diphenyl-4,9-dioxa-3,10-disiladodecaneC35H52O3Si2[α]D25=-5.1 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (5S,6S)

(3S,4S)-5-(Benzyloxy)-4-(tert-butyldiphenylsilyloxy)-3-methylpentan-1-olC29H38O3Si[α]D25=-8.5 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (3S,4S)

((2S,3S)-1-(Benzyloxy)-5-iodo-3-methylpentan-2-yloxy)(tert-butyl)diphenylsilaneC29H37IO2Si[α]D25=-6.0 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2S,3S)

(E)-Ethyl 3-((2R,3S)-3-(2-(benzyloxy)ethyl)oxiran-2-yl)acrylateC16H20O4[α]D25=-7.2 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2R,3S)

(4S,5S,E)-Ethyl 7-(benzyloxy)-5-hydroxy-4-methylhept-2-enoateC17H24O4[α]D25=-14.4 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (4S,5S,E)

((2S,3S)-3-((2S,3S)-5-(Benzyloxy)-3-(tert-butyldimethylsilyloxy)pentan-2-yl)oxiran-2-yl)methanolC21H3604Si[α]D25=-24.5 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (S,S,S,S)

(2R,3R,4S,5S)-7-(Benzyloxy)-5-(tert-butyldimethylsilyloxy)-2,4-dimethylheptane-1,3-diolC22H40O4Si[α]D25=-14.5 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (2R,3R,4S,5S)

((3S,4S)-1-(Benzyloxy)-4-((4R,5R)-2,2,5-trimethyl-1,3-dioxan-4-yl)pentan-3-yloxy)(tert-butyl)dimethylsilaneC25H44O4Si[α]D25=-23.5 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (5S, 10S, 11S, 7E)

(5S,10S,11S,Z)-11-(Benzyloxymethyl)-2,2,3,3,10,14,14-heptamethyl-13,13-diphenyl-5-((S)-1-((4R,5R)-2,2,5-trimethyl-1,3-dioxan-4-yl)ethyl)-4,12-dioxa-3,13 disilapentadec-7-eneC47H72O5Si2[α]D25=-15.5 (c 1.0, CHCl3)Source of chirality: Sharpless epoxidationAbsolute configuration: (5S, 4R, 5R)