Total synthesis of (4S,10R)-4-hydroxy-10-methyl-11-oxododec-2-en-1,4-olide and related bioactive marine butenolides

Marine-derived microorganisms produce structurally diverse butenolides possessing a variety of bioactivities. Described here is the total synthesis of (4S,10R)-4-hydroxy-10-methyl-11-oxododec-2-en-1,4-olide and a related butenolide containing anti stereochemistry at C10–C11. A three-module coupling strategy has been established for synthesis of the stereoisomers of the naturally occurring butenolides by assembling the C3–C7 and C9–C12 fragments via double alkylation of a 1,3-dithiane. The C10–C11 stereochemistry could be easily controlled by an asymmetric aldol condensation, while the butenolide unit was efficiently constructed according to the ring-closing metathesis protocol.

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(4S,10R,11S)-4,11-Dihydroxy-10-methyldodec-2-en-1,4-olideC13H22O3Diastereomer ratio: (4S,10R,11S):(4R,10R,11S) ⩾ 91:9[α]D23=+78.0 (c 0.10, MeOH)Source of chirality: asymmetric reactionAbsolute configuration: (4S,10R,11S)

(4S,10R)-4-Hydroxy-10-methyl-11-oxododec-2-en-1,4-olideC13H20O3Diastereomer ratio: (4S,10R):(4R,10R) ⩾ 91:9[α]D23=+32.0 (c 0.10, MeOH)Source of chirality: asymmetric reactionAbsolute configuration: (4S,10R)