A Sequential Two‐Component Etherification/Oxa‐Conjugate Addition Reaction: Asymmetric Synthesis of (+)‐Leucascandrolide A Macrolactone

Abstract

A smooth operator: The asymmetric synthesis of the macrolactone of (+)‐leucascandrolide A (see structure) has been accomplished through a convergent route (longest linear sequence of 14 steps) in 20 % overall yield. The assembly of the 1,5‐bis(tetrahydropyran) core in a single operation provides the most concise synthetic approach developed to date.

Muscarine, imidazole, oxazole, and thiazole alkaloids

“…Recently, three different strategies have been developed for construction of the macrolactone core of (+)-leucascandrolide A. [219][220][221] (+)-Phorboxazoles A 235 and B 236, isolated originally from an extract of the sponge Phorbas sp., are two 21-membered macrolides possessing a novel macrocyclic architecture. Recently, a diminutive form of (+)-phorboxazole A, hemiphorboxazole A 237 was isolated from the same marine sponges.…”

Iodocyclization and Prins-Type Macrocyclization: An Efficient Formal Synthesis of Leucascandrolide A

“…Currently, there is no natural source of leucascandrolide A. Based on its impressive biological activity, inaccessibility from natural sources, and structural complexity associated with ample synthetic challenges, the construction of leucascandrolide A has spurred considerable synthetic interest, resulting in several total and formal syntheses. − …”

New trends in bismuth-catalyzed synthetic transformations

“…The same group reported a one-pot diastereoselective sequential two-component etherification, followed by an oxaconjugate addition. 36 The reaction of an anomeric acetal with a trimethylsilyloxy diene afforded a bis(tetrahydropyran) core used in the total synthesis of (+)-leucascandrolide A (Scheme 28). Bi(NO) 3 was used as a Brønsted acid source.…”