Synthesis of (+) and (-)-Streptomyces coelicolor butanolide 5 (SCB-5)

Abstract

Various 1-(1-hydroxyalkyl) paraconyl alcohols are important signaling molecules within antibiotics production in Streptomyces sp. Intending developing a flexible convergent chemical synthesis of such butanolides, a zwitterionic aza-Claisen rearrangement was chosen as reliable strategy generating the central stereotriad. Reaction of enantiopure N-allyl pyrrolidines and 4-phenylbutenoic acid fluoride delivered defined configured amides displaying the 2,3,1’ stereotriads. The configuration was determined by the allyl alcohol moiety indicating a complete remote stereo control. Amide removal by iodolactonization and proceeding reductions, halocyclization and elimination gave key alkylidene tetrahydrofuran derivatives. Stepwise degradation of the olefins through ozonolysis, reductive work-up and protecting group removal delivered both enantiomers of the target Streptomyces coelicolor butanolide 5.