Total Synthesis of (–)-Tetracycline

Keywords

(–)-tetracycline - tetracycline antibiotics - epoxide opening Stevens rearrangement - reductive transposition - benzocyclobutene Diels–Alder reaction - auto-oxidation

Significance

The tetracyclines are a class of natural products and semisynthetic analogues that serve as antibiotics in human and veterinary medicine. Myers and co-workers describe a synthetic route to (–)-tetracycline. Their modular synthetic sequence allows for preparation of several 6-deoxytetracycline analogues, which culminated in development of the drug Eravacycline.

Comment

Ester A, accessed from benzoic acid in four steps, was converted into ketone C through 1,2-addition of heteroaryl anion B. The product was transformed into tricyclic ketone D by treatment with catalytic lithium triflate in toluene. The authors propose that the transformation proceeds through opening of the epoxide and subsequent Stevens rearrangement. Pentacycle I was accessed by a Diels–Alder reaction of enone G with benzocyclobutene H.

Publication History

Article published online:
21 November 2024