Absolute Configuration and Cytotoxicity of a New Vouacapane Diterpenoid from Coulteria velutina

Abstract

Objective: Determine the structure, absolute configuration, and antiproliferative activity of a new furan diterpenoid isolated from the leaves of Coulteria velutina (Britton & Rose) Sotuyo & G.P.Lewis (Fabaceae). Methods: The structures of the natural product and those of 2 derivatives were established mainly by nuclear magnetic resonance spectroscopy, while their absolute configurations were established using vibrational circular dichroism involving comparison of the experimental and calculated spectra of a rigid derivative. Results: Isolation of (−)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-6-[( E)- p-coumaroyloxy]vouacapan-18-oic acid (1), an undescribed secondary metabolite from the leaves of C velutina, is reported hereafter. Hydrolysis of 1 provided (+)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-6-hydroxyvouacapan-18-oic acid (2), identical to a diterpenoid isolated from Caesalpinia echinata, but whose absolute configuration remained undetermined. Subsequent lactonization of 2 yielded (+)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-vouacapan-6,18-olide (3). The absolute configurations of compounds 1–3 were established by vibrational circular dichroism studies of 3. In addition, the antiproliferative activity of the natural product 1 against HeLa, MDA-MB-231, Caco-2, and NIH/3T3 cell lines is reported. Conclusions: The leaves of C velutina yielded the new vouacapane 1. It showed weak antiproliferative activity against HeLa and MDA-MB-231 cancer cell lines (IC50 = 92.2 and 106.2 μg/mL, respectively), but was also weakly active against the NIH/3T3 healthy cell line (IC50 value of 127.6 µg/mL). Its absolute configuration was determined by vibrational circular dichroism analysis of the conformationally rigid compound 3. This derivative can be used as a reference for the absolute configuration of related vouacapanes. In addition, this is the first phytochemical investigation of C velutina.