Work

Synthesis of Indole Analogues of the Natural Schweinfurthins

Year: 2013

Type: article

Abstract: An interest in the schweinfurthins, natural stilbenes with significant antiproliferative activity, has prompted efforts to prepare a set of indole analogues. To approach the desired compounds through a Horner-Wadsworth-Emmons condensation, new indole derivatives bearing a phosphonomethyl substituent in the B-ring were required. The parent indole system with the necessary substitution pattern was obtained through Stobbe condensation and cyclization. A prenyl substituent was incorporated at the C3 position of a 4,6-disubstituted indole through a highly regioselective electrophilic aromatic substitution reaction, while metalation and alkylation provided the C2-prenylated indole. After introduction of the phosphonate group through classical reactions, the new indole phosphonates were found to undergo the desired condensation with nonracemic aldehydes representing the schweinfurthin left half. This approach provides facile access to new heteroaromatic analogues of the natural schweinfurthins and should be applicable to many other natural stilbenes as well.

Source: The Journal of Organic Chemistry

DOI: 10.1021/jo4014244

Authors: John G. Kodet, David F. Wiemer

Institution: University of Iowa

Language: English

Topic: Synthesis of Indole Derivatives

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Cancer Institute

Award: G3767283544