Ten-Year Retrospective of the Vanderbilt Institute of Chemical Biology Chemical Synthesis Core.

Chemical synthesis has been described as a central science. Its practice provides access to the chemical structures of known and/or designed function. In particular, human health is greatly impacted by synthesis that enables advancements in both basic science discoveries in chemical biology as well as translational research that can lead to new therapeutics. To support the chemical synthesis needs of investigators across campus, the Vanderbilt Institute of Chemical Biology established a chemical synthesis core as part of its foundation in 2008. Provided in this Review are examples of synthetic products, known and designed, produced in the core over the past 10 years.

A Modular Construction of Epidithiodiketopiperazines.

Epidithiodiketopiperazines (ETPs) possess remarkably diverse biological activities and have attracted significant synthetic attention. The preparation of analogues is actively pursued; however, they are structurally challenging, and more direct and modular methods for their synthesis are desirable. To this end, the utility of a bifunctional triketopiperazine building block for the straightforward synthesis of ETPs is reported. A modular strategy consisting of enolate alkylation followed by site-selective nucleophile addition enables the concise synthesis of (±)-hyalodendrin and a range of analogues.

An enantioselective synthesis of α-alkylated pyrroles via cooperative isothiourea/palladium catalysis.

Herein we describe the direct enantioselective Lewis base/Pd catalysed α-allylation of pyrrole acetic acid esters. This provides high isolated yields of highly enantioenriched products and exhibits broad reaction scope with respect to both reaction partners. The products can be readily elaborated in a manner which points towards potential applications in target directed synthesis.