Synthesis of the C8–C16 fragment of amphidinolide R

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An asymmetric synthesis of the C8–C16 fragment with several stereogenic centers of amphidinolide R, is described. The key reaction, Sharpless asymmetric epoxidation has provided the basis for generation of the required stereocenters. The target fragment was accomplished in a convergent manner in nine steps (longest linear synthesis of the sequence) and 32% overall yield was obtained starting from 2-butene-1,4-diol.

(2R,3R)-4-(Benzyloxy)-2-methylbutane-1,3-diolC12H18O3[α]D27 = −14.4 (c 1.0, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (2R,3R)

(2R,3R)-2,4-Bis((tert-butyldimethylsilyl)oxy)-3-methylbutan-1-olC17H40O3Si2[α]D27 = +3.1 (c 1.1, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (2R,3R)

(2R,3R)-2,4-Bis((tert-butyldimethylsilyl)oxy)-3-methylbutanalC17H38O3Si2[α]D27 = +2.2 (c 1.09, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (2R,3R)

(2R,3S)-3-((tert-Butyldimethylsilyl)oxy)-2-methylpent-4-en-1-olC12H26O2Si[α]D27 = +26.8 (c 1.34, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (2R,3S)

Dimethyl ((3R,4R)-3,5-bis((tert-butyldimethylsilyl)oxy)-4-methyl-2-oxopentyl)phosphonateC20H45O6PSi2[α]D27 = +23.4 (c 1.20, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (3R,4R)

(6R,7R,11R,12S,E)-7-((tert-Butyldimethylsilyl)oxy)-2,2,3,3,6,11,14,14,15,15-decamethyl-12-vinyl-4,13-dioxa-3,14-disilahexadec-9-en-8-oneC30H62O4Si3[α]D27 = +10.1 (c 1.0, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (6R,7R,11R,12S,E)

(6R,7R,8R,11R,12S,E)-7-((tert-Butyldimethylsilyl)oxy)-2,2,3,3,6,11,14,14,15,15-decamethyl-12-vinyl-4,13-dioxa-3,14-disilahexadec-9-en-8-olC30H64O4Si3[α]D27 = +19.6 (c 0.65, CHCl3)Source of chirality: (+)-Diethyl l-tartrateAbsolute configuration: (6R,7R,8R,11R,12S,E)