Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure-activity relationships of
S B Singh1, P L Graham, R A Reamer
1Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. sheo_singh@merck.com
Bioorganic & Medicinal Chemistry Letters
|November 27, 2001
Abstract:
2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC(50) value of 4.6 microM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% overall yield using a Diels-Alder approach. Several analogues of this compound were prepared. Isolation, synthesis and HRV 3C-protease structure-activity relationships of these compounds have been described.


