Determination of the Absolute Configurations of Pharmacological Natural Products via Density Functional Theory Calculations of Vibrational Circular Dichroism: The New Cytotoxic Iridoid Prismatomerin

Abstract

A new highly cytotoxic iridoid has very recently been isolated from Prismatomeris tetrandra and shown to have the structure 3, similar to that of the iridoid oruwacin, 2. We report the determination of the absolute configuration (AC) of the new iridoid, prismatomerin, using vibrational circular dichroism (VCD) spectroscopy. The VCD spectrum of the acetate derivative of 3, 4, is analyzed using the Stephens theory of VCD and density functional theory (DFT). The AC of the naturally occurring 3 is shown to be 1R,5S,8S,9S,10S, identical to that of the naturally occurring iridoid plumericin, 1, also determined using VCD spectroscopy. The [alpha]D values of the natural products 3 and 1 are negative and positive, respectively. Since the ACs of 3 and 1 are identical, it follows that the AC of 3 cannot be correctly determined by empirical comparison of the signs of the [alpha]D values of 3 and 1.