Synthesis of the C12−C19 Fragment of (+)-Peloruside A through a Diastereomer-Discriminating RCM Reaction

Abstract

[reaction: see text]. A short and efficient asymmetric synthesis of the C12-C19 fragment of the cytotoxic macrolide (+)-peloruside A has been achieved via a highly diastereomer-discriminating RCM of alpha-branched but-3-enoate ester of a methallylic alcohol derived from hydrolytically resolved (S)-(-)-propylene oxide.

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

“…Presumably, the identity of the protecting groups on this substrate (i.e., R 2 and R 3 ) would be critical to the success of the reaction. After formation of the epoxide, the bulky trityl ether was envisioned to direct the subsequent ring-opening to the distal carbon [19–22]. Alkene 6 would ultimately be formed by a Myers alkylation [23] of (+)-pseudoephedrine derived amide 7 with allylic iodide 8 .…”

“…A Myers alkylation and a reagent-controlled Shi epoxidation were used to construct this compound in a highly stereoselective fashion. The bulky trityl group of 25 was intended to serve as a means of directing a ring-opening reaction to the distal carbon of the epoxide [19–22]. However, an unanticipated Lewis acid promoted Payne rearrangement intervened, producing alcohol 26 instead of the expected regioisomer 27 .…”

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

“…Since then, the RCM of butenoates has been used in methodology and synthetic applications [170][171][172][173][174][175][176][177][178][179][180]. It is quite amazing that despite this kind of ring closure appears to …”

Microtubule-Stabilizing Natural Products as Promising Cancer Therapeutics

“…The first synthesis of the natural enantiomer was recently completed by Taylor [117]. In addition, a number of synthetic efforts are underway toward total syntheses [118,119]. NMR studies have recently determined the bioactive conformation of peloruside bound to microtubules [120] which may aide in the future design of analogs.…”