A Stereocontrolled Total Synthesis of Lipoxin B4 and Its Biological Activity As a Pro-Resolving Lipid Mediator of Neuroinflammation

Overview

Journal Chemistry

Specialty Chemistry

Date 2022 May 2

PMID 35491534

Authors

C Frank Lee

Carla E Brown

Alexander J Nielsen

Changmo Kim

Izhar Livne-Bar

Philip J Parsons

Christophe Boldron

Francois Autelitano

Donald F Weaver

Jeremy M Sivak

Mark A Reed

Affiliations

Soon will be listed here.

Abstract

Two stereocontrolled, efficient, and modular syntheses of eicosanoid lipoxin B4 (LXB ) are reported. One features a stereoselective reduction followed by an asymmetric epoxidation sequence to set the vicinal diol stereocentres. The dienyne was installed via a one-pot Wittig olefination and base-mediated epoxide ring opening cascade. The other approach installed the diol through an asymmetric dihydroxylation reaction followed by a Horner-Wadsworth-Emmons olefination to afford the common dienyne intermediate. Finally, a Sonogashira coupling and an alkyne hydrosilylation/proto-desilylation protocol furnished LXB in 25 % overall yield in just 10 steps. For the first time, LXB has been fully characterized spectroscopically with its structure confirmed as previously reported. We have demonstrated that the synthesized LXB showed similar biological activity to commercial sources in a cellular neuroprotection model. This synthetic route can be employed to synthesize large quantities of LXB , enable synthesis of new analogs, and chemical probes for receptor and pathway characterization.

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