Total Synthesis of Psammaplysins A, M, O, and Q and Ceratinamide A

Abstract

The psammaplysins are a unique class of brominated marine alkaloids bearing a signature 5/7-spiroisoxazolineoxepine core linked to a variable tyramine-derived unit. Here, we report the total synthesis of several members of this family via a dipolar cycloaddition between an in situ generated nitrile oxide and an unusual seven-membered enediol diether dipolarophile. Carefully orchestrated oxidative transformation toward the fully functionalized spirocycle and direct coupling with tyramine-derived amines provides access to five representative family members, psammaplysins A, M, O, and Q and ceratinamide A, the latter four for the first time. Additionally, kinetic resolution of a late-stage intermediate enables the first asymmetric synthesis of (−)-psammaplysin A, thereby confirming its absolute configuration.

Baeyer–Villiger oxidation: a promising tool for the synthesis of natural products: a review

“…In 2023, Morrow & Smith presented the total synthesis of psammaplysins A 65 and first total synthesis of psammaplysin O, Q, M, (65 and 67) and ceratinamide A 67 by utilizing Baeyer Villiger oxidation as a fundamental step to convert 6-membered ketone 56 into 7-membered lactone 57. 91 The synthesis was started with the preparation of lactone 57 in 99% yield from ketone 56 via subsequent Baeyer–Villiger oxidation with m -CPBA. Benzyloxymethylenation of lactone 57 afforded enol ether 58 in 53% yield ( E / Z = 1 : 1), ( E )-58 was further treated with compound 59 under optimized conditions ( i -Pr 2 NEt, MTBE) to furnish a single diastereomer spiroisoxazoline 60 in 44% yield.…”