Synthetic approaches toward ecteinascidins. Part 1. Preparation of an (E)-2-arylidene-3-benzyl-1,5-imino-3-benzazocin-4-one having a protected phenol in the E-ring

Abstract

A synthetic strategy for the preparation of ecteinascidins isolated from the Caribbean tunicate Ecteinascidia turbinata and an efficient synthesis of a key tricyclic lactam intermediate 32 are described. The key step is the intramolecular cyclization of the allylic alcohol 15 to the (E)-1,5-imino-3-benzazocine 16. Cyclization of 15 (R = Me, Bn) afforded the desired product 16 in good yield. However, treatment of 15 (R = MOM) under acidic conditions gave compound 18 in high yield, the structure of which was determined by X-ray crystallography. Finally, 16 was converted into (E)-N-methyltricyclic lactam 32 that can serve as a synthetic precursor of ecteinascidins.