Scalable Total Synthesis of (+)-Desmethylxestospongin B

TL;DR

This paper describes an improved and scalable synthesis of the natural product (+)-desmethylxestospongin B, increasing yield and simplifying key steps.

Contribution

The paper introduces a more efficient synthetic route with higher yield and reduced reliance on complex stereochemical methods.

Findings

The total yield of (+)-desmethylxestospongin B was increased by 50% compared to prior methods.

A stereoselective epoxidation method was used to streamline the synthesis of a key intermediate.

The updated synthesis produced 0.37 g of the compound, suitable for further biological studies.

Abstract

Herein, the execution of synthetic strategies solving
scalability issues observed in the original route is reported, increasing
the total yield by 50% compared to the previously disclosed synthesis.
A notable restructuring of the route’s initial steps to reach
a common allylic alcohol intermediate employs a highly stereoselective
epoxidation method and avoids superfluous protecting group manipulations
while limiting dependence on kinetic resolution in establishing stereochemistry
for four of the six chiral centers in (+)-desmethylxestospongin B.
Different protecting group strategies to avoid problems with their
subsequent removal were considered and enacted; to this end, material
was retained as byproducts were suppressed. While the lactam semireduction
under Birch conditions requires further investigation, the updated
synthesis of (+)-desmethylxestospongin B reported here made it more
scalable, affording 0.37 g of this natural product for continued biological
studies.

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