Stereoselective synthesis of a C19–C26 fragment of amphidinolides G and H

A short, stereoselective synthesis of the C19–C26 segment of the structure of the cytotoxic macrolides amphidinolides G and H is reported. A precursor from the chiral pool has been used as the starting material.

A short, stereoselective synthesis of the C19–C26 segment of the structure of the cytotoxic macrolides amphidinolides G and H is reported.Figure optionsDownload as PowerPoint slide

(3R,5R)-5-(tert-Butyldiphenylsilyloxymethyl)-3-methyldihydrofuran-2(3H)-oneC22H28O3SiEe = 100%[α]D = −13.4 (c 1.1, CHCl3)Absolute configuration: (3R,5R)

(4R,6R)-7-(tert-Butyldiphenylsilyloxy)-6-hydroxy-4-methylhept-2E-enoic acid ethyl esterC26H36O4SiEe = 100%[α]D = −14.0 (c 0.9, CHCl3)Absolute configuration: (4R,6R)

(2R,3S,4R,6R)-7-(tert-Butyldiphenylsilyloxy)-2,3,6-trihydroxy-4-methylheptanoic acid ethyl esterC26H38O6SiEe = 100%[α]D = +9.1 (c 1.5, CHCl3)Absolute configuration: (2R,3S,4R,6R)

(4R,5S)-5-[(2R,4R)-5-(tert-Butyldiphenylsilyloxy)-4-hydroxypent-2-yl]-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid ethyl esterC29H42O6SiEe = 100%[α]D = −2.0 (c 1.7, CHCl3)Absolute configuration: (4R,5S,2′R,4′R)

(4R,5S)-5-[(2R,4R)-5-(tert-Butyldiphenylsilyloxy)-4-(triethylsilyloxy)pent-2-yl]-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid ethyl esterC35H56O6Si2Ee = 100%[α]D = +7.1 (c 1.6, CHCl3)Absolute configuration: (4R,5S,2′R,4′R)

(4R,5S)-5-[(2R,4R)-5-(tert-Butyldiphenylsilyloxy)-4-(triethylsilyloxy)pent-2-yl]-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid N-methoxy-N-methylamideC35H57NO6Si2Ee = 100%[α]D = +13.2(c 1.1, CHCl3)Absolute configuration: (4R,5S,2′R,4′R)

1-{5-[(2R,4R)-5-(tert-Butyldiphenylsilyloxy)-4-(triethylsilyloxy)pent-2-yl]-(4R,5S)-2,2-dimethyl-[1,3]dioxolan-4-yl}-ethanoneC34H54O5Si2Ee = 100%[α]D = +17.7 (c 0.8, CHCl3)Absolute configuration: (4R,5S,2′R,4′R)