Total Synthesis of the Psammaplysins: Evolution of a Dipolar Cycloaddition Approach

Abstract

The psammaplysins are a unique group of bromotyrosine-derived natural products isolated from the Psammaplysilla genus of marine sponges. Aside from the various biological activities they possess, synthetic chemists have been drawn to the family for decades due to the intriguing 5/7-spiroisoxazoline-oxepine core common to all members. Herein, we describe our synthetic approach towards the psammaplysin family in the context of this broader work. Our route centers upon the use of a carefully choreographed alkoxymethylenation/1,3-dipolar cycloaddition to construct the key spiroisoxazoline-oxepine ring system, followed by its functionalization and divergent coupling to access various family members. We also detail the development of the first asymmetric approach to this class of marine natural products.

1 Introduction

2 Initial Synthetic Approach and Challenges Encountered

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

4 Development of an Asymmetric Solution to the Family

5 Conclusions and Outlook

Key words

kinetic resolution - dipolar cycloaddition - nitrile oxide - total synthesis - psammaplysin - alkaloids

Publication History

Received: 15 November 2024

Accepted after revision: 27 January 2025

Accepted Manuscript online:
27 January 2025

Article published online:
31 March 2025

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