Formal total synthesis of (+)-didemniserinolipid B

The formal total synthesis of (+)-didemniserinolipid B, a marine tunicate possessing a 6,8-dioxabicyclo[3.2.1]octane framework, was accomplished starting from l-(+)-tartaric acid. The key transformations in the synthesis include the elaboration of a γ-hydroxy-amide readily obtained by desymmetrization of tartaric acid bis-amide via the controlled addition of a Grignard reagent followed by stereoselective reduction of the resulting ketone.

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(4R,5R)-5-(6-(Benzyloxy)hexanoyl)-N,N,2,2-tetramethyl-1,3-dioxolane-4-carboxamideC21H31NO5[α]D = +10.1 (c 3.8, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(R)-Methyl 2-((4R,5R)-5-(5-(benzyloxy)pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-hydroxyacetateC21H33NO5[α]D = +14.3 (c 1.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(S)-Methyl 2-((4R,5R)-5-(5-(benzyloxy)pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-hydroxyacetateC21H33NO5[α]D = +27.9 (c 2.0, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(R)-2-(Benzyloxy)-2-((4S,5R)-5-(5-(benzyloxy)pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethanolC26H36O5[α]D = −3.7 (c 1.9, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(R)-1-(Benzyloxy)-1-((4R,5R)-5-(5-(benzyloxy)pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-19-hydroxynonadecan-4-oneC43H68O6[α]D = +14.1 (c 1.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

15-((1R,2R,5R,7R)-2-(Benzyloxy)-7-(5-(benzyloxy)pentyl)-6,8-dioxabicyclo[3.2.1]octan-5-yl)pentadecan-1-olC40H62O5[α]D = +23.5 (c 0.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration (1R,2R,5R,7R)