Total synthesis of (-)-mucocin and studies toward the asymmetric total synthesis of brianthein A

Public Deposited

Analytics

Last Modified

Creator

Abstract

A highly convergent asymmetric total synthesis of antitumor acetogenin natural product (-)-mucocin is described. This approach combined asymmetric glycolate aldol additions with ring-closing metatheses to construct cyclic ethers. In addition, a relay ring-closing metathesis strategy was successfully applied to the regioselective formation of an intermediate dihydrofuran. Finally, the two complex alkene fragments were coupled via a selective cross metathesis reaction. During efforts toward the asymmetric total synthesis of bioactive natural product brianthein A, a novel asymmetric aldol addition-thioimide transesterificationdianionic Claisen rearrangement strategy was developed. This strategy showcased the utility and versatility of the thiazolidinethione-mediated propionate aldol methodology previously developed in the Crimmins laboratories, and allowed rapid access to several complex intermediates containing all-carbon quaternary stereocenters in high yield and diastereoselectivity. Furthermore, synthesis of the highly functionalized trans-fused 6,10-bicyclic core of brianthein A was accomplished. By utilizing ring-closing metathesis as the key cyclization strategy, along with introducing an appropriate conformational constraint to the cyclization substrate, formation of the challenging ten-membered carbocycle was successful.

Date of publication

DOI

Resource type

Rights statement

Advisor

Degree granting institution

Language

Access right

Date uploaded

Relations

Thumbnail	Title	Date Uploaded	Visibility	Actions
	Total synthesis of (-)-mucocin and studies toward the asymmetric total synthesis of brianthein A	2019-04-10	Public	Download