A formal, stereoselective synthesis of the natural tetrahydropyran derivative ophiocerin D

A short, formal stereoselective synthesis of the naturally occurring tetrahydropyran derivative ophiocerin D is reported. The four stereocenters of the molecule were created with the aid of two Sharpless asymmetric dihydroxylations.

A short, formal stereoselective synthesis of the naturally occurring tetrahydropyran derivative ophiocerin D is reported.Figure optionsDownload as PowerPoint slide

Ethyl (2E,4R,5R)-5-hydroxy-4-(4-methoxyphenoxy)hex-2-enoateC15H20O5Ee = 92%[α]D = −58.8 (c 1, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2E,4R,5R)

Ethyl (2E,4R,5R)-5-(tert-butyldimethylsilyloxy)-4-(4-methoxyphenoxy)hex-2-enoateC21H34O5SiEe = 92%[α]D = +8.8 (c 1, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2E,4R,5R)

Ethyl (2R,3R,4R,5R)- 5-(tert-butyldimethylsilyloxy)-2,3-dihydroxy-4-(4-methoxyphenoxy)hexanoateC21H36O7SiEe = 96%[α]D = +19.5 (c 1, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2R,3R,4R,5R)

Ethyl (2R,3S,4R,5R)-5-(tert-butyldimethylsilyloxy)-2,3-bis(methoxymethoxy)-4-(4-methoxyphenoxy)hexanoateC25H44O9SiEe = 96%[α]D = +2 (c 1.3, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2R,3S,4R,5R)

(2S,3R,4R,5R)-5-(tert-Butyldimethylsilyloxy)-2,3-bis(methoxymethoxy)-4-(4-methoxyphenoxy)hexan-1-olC23H42O8SiEe = 96%[α]D = +15 (c 0.86, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2S,3R,4R,5R)

(2R,3S,4R,5S)-4,5-Bis(methoxymethoxy)-3-(4-methoxyphenoxy)-2-methyltetrahydro-2H-pyranC17H26O7Ee = 96%[α]D = −17.3 (c 0.9, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2R,3S,4R,5S)

(2R,3S,4S,5S)-4,5-Bis(methoxymethoxy)-3-(4-methoxyphenoxy)-2-methyltetrahydropyran-3-olC10H20O6Ee = 96%[α]D = −6.2 (c 1.7, CHCl3)Source of chirality: asymmetric Sharpless dihydroxylationAbsolute configuration: (2R,3S,4S,5S)