Work

Concise Syntheses of the Abyssinones and Discovery of New Inhibitors of Prostate Cancer and MMP-2 Expression

Year: 2010

Type: article

Abstract: Hydrogen-bonding catalysis is an emerging field that facilitates rapid access to medicinally relevant enantioenriched small molecules. Here, we report the first asymmetric total syntheses of four members of the abyssinone class of natural products (I, II, III, and IV 4´-OMe) via quinine- or quinidine-derived thiourea-catalyzed intramolecular conjugate additions of β-keto ester alkylidenes. This concise strategy includes a tandem deprotection/decarboxylation final step that delivers all four natural products and their corresponding antipodes. A preliminary evaluation of all of these small molecules against a metastatic human prostate cancer cell line has identified that these compounds selectively and differentially inhibit cell growth and downregulate the expression of matrix metalloproteinase-2 (MMP-2) at non-toxic concentrations.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/ml100110x

Authors: Rebecca L. Farmer, Margaret M. Biddle, Antoinette E. Nibbs, Xiaoke Huang, Raymond C. Bergan, Karl A. Scheidt

Institutions: Northwestern University, Chemistry of Life Processes Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute on Aging, National Cancer Institute