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Bioorg Med Chem. 2011 Mar 1;19(5):1708-13. doi: 10.1016/j.bmc.2011.01.027. Epub 2011 Jan 19.

Unexpected stereochemical tolerance for the biological activity of tyroscherin.

Author information

1
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.

Abstract

Here we describe the concise syntheses of the 15 diastereomers and key analogs of the natural product tyroscherin. While systematic analysis of the analogs clearly demonstrated that the hydrocarbon tail is important for biological activity, structure-activity relationship studies of the complete tyroscherin diastereoarray revealed a surprisingly expansive stereochemical tolerance for the cytotoxic activity. Our results represent a departure from the tenet that biological activity is constrained to a narrow pharmacophore, and highlight the recently emerging appreciation for stereochemical flexibility in defining the essential structural elements of biologically active small molecules.

PMID:
21315614
PMCID:
PMC3056444
DOI:
10.1016/j.bmc.2011.01.027
[Indexed for MEDLINE]
Free PMC Article

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