RESUMO
Several dozen spirocyclic sesquiterpenoids known as the bromo-chamigrenes have been isolated to date. Yet, despite their unique structures, synthetic efforts toward this collection have been modest. Herein, we outline two strategies to generate their skeletons based on (1) a biomimetic bromonium-induced polyene cyclization using BDSB (Et2SBr·SbCl5Br) and (2) a Diels-Alder reaction which ultimately delivered four members of the class. In addition, X-ray crystallography reveals that one member has a structure in need of revision.
RESUMO
A highly convergent total synthesis of the potent polyketide macrolide rhizopodin has been achieved in 29 steps by employing a concise strategy that exploits the molecule's C2 symmetry. Notable features of this convergent approach include a rapid assembly of the macrocycle through a site-directed sequential cross-coupling strategy and the bidirectional attachment of the side chains by means of Horner-Wadsworth-Emmons (HWE) coupling reactions. During the course of this endeavor, scalable routes for synthesis of three main building blocks of similar complexity were developed that allowed for their stereocontrolled construction. This modular route will be amenable to the development of syntheses of other analogues of rhizopodin.
Assuntos
Actinas/química , Macrolídeos/síntese química , Oxazóis/síntese química , Actinas/metabolismo , Ciclização , Dimerização , Macrolídeos/química , Oxazóis/químicaRESUMO
A convergent synthesis of the central C8-C22 core of the potent macrolide antibiotic rhizopodin is reported. Notable features of the stereocontrolled approach include an asymmetric reverse prenylation of an alcohol using a method of Krische, a thiazolium catalyzed transformation of an epoxyaldehyde as described by Bode, and a late-stage oxazole formation from advanced intermediates. This route demonstrates the applicability of these methodologies in complex natural product synthesis.
