Enantioselective total synthesis of iso-cladospolide B, cladospolide C and cladospolide B from tartaric acid

The enantioselective synthesis of the natural products cladospolide B, cladospolide C, and iso-cladospolide B has been accomplished from tartaric acid. Key reactions in the synthetic sequence include the elaboration of a γ-hydroxy amide derived from tartaric acid via alkene cross metathesis, Yamaguchi lactonization, and ring closing metathesis.

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(4S,5S)-N-Methoxy-N,2,2-trimethyl-5-((5S,11S)-2,2,3,3,11,13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadecan-5-yl)-1,3-dioxolane-4-carboxamideC28H59NO6Si2[α]D = +9.6 (c 1.8, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (4S,5S,5′S,11′S)

(4S,5S)-N-Methoxy-N,2,2-trimethyl-5-((5S,11R)-2,2,3,3,11,13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadecan-5-yl)-1,3-dioxolane-4-carboxamideC28H59NO6Si2[α]D = +2.6 (c 2.1, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (4S,5S,5′S,11′R)

((4R,5S)-2,2-Dimethyl-5-((5S,11S)-2,2,3,3,11,13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadecan-5-yl)-1,3-dioxolan-4-yl)methanolC26H56O5Si2[α]D = −4.3 (c 1.9, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (4R,5S,5′S,11′S)

((4R,5S)-2,2-Dimethyl-5-((5S,11R)-2,2,3,3,11,13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadecan-5-yl)-1,3-dioxolan-4-yl)methanolC26H56O5Si2[α]D = −18.9 (c 1.5, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (4R,5S,5′S,11′R)

(5S,11S)-5-((4S,5S)-5-(Iodomethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2,3,3,11,13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadecaneC26H55IO4Si2[α]D = +10.3 (c 0.6, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5S,11S,4′S,5′S)

(5S,11R)-5-((4S,5S)-5-(Iodomethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2,3,3,11,13,13,14,14-nonamethyl-4,12-dioxa-3,13-disilapentadecaneC26H55IO4Si2[α]D = −11.6 (c 1.3, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5S,11R,4′S,5′S)

(2S,8S,9S)-8-(tert-Butyldimethylsilyloxy)undec-10-ene-2,9-diolC17H36O3Si[α]D = +2.5 (c 1.2, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (2S,8S,9S)

(2R,8S,9S)-8-(tert-Butyldimethylsilyloxy)undec-10-ene-2,9-diolC17H36O3Si[α]D = −10.4 (c 1.8, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (2R,8S,9S)

(S)-5-((5S,11S)-2,2,3,3,11,13,13,14,14-Nonamethyl-4,12-dioxa-3,13-disilapentadecan-5-yl)furan-2(5H)-oneC24H48O4Si2[α]D = −80.7 (c 0.8, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5S,11S)