Stereocontrolled and Adaptable Synthesis of (-)-Aspergilone A via the Key Intermediate (+)-Phenol A.

ABSTRACT: We report the first total synthesis of (-)-aspergilone A, a citrinin-type azaphilone, and the determination of the absolute configuration of naturally occurring (+)-aspergilone A. The synthesis is centered around phenol A, a substructure of citrinin-type azaphilones, as the key intermediate. (+)-Phenol A was constructed using two sequential 1,2-boronate rearrangements with exceptional stereocontrol. Formally, this approach allows for the construction of all stereoisomers of phenol A without the need to change the synthetic procedure. The synthesis was completed in 11 steps with a total yield of 15.7% and >99% ee. The absolute configuration of (+)-aspergilone A was determined to be 3R, 4S.

SUBMITTER: Langer MK 

PROVIDER: S-EPMC12481563 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature