Absolute configuration of (-)-gambogic acid, an antitumor agent

Abstract

(-)-Gambogic acid (1), a biologically active "caged xanthone" from gamboge, the dried resin of Garcinia hanburyi, is of interest as a potential anticancer agent. The planar structure of (-)-gambogic acid has been determined previously by analysis of its detailed NMR data and confirmed by single-crystal X-ray diffraction, with the absolute configuration at C-13 deduced as R through a series of chemical degradations. Using (-)-morellic acid (2), an analogue of (-)-gambogic acid, as a model compound, the 5R, 7S, 10aS, 13R, 27S absolute configuration of (-)-gambogic acid was determined for the first time by comparison of physical and spectroscopic data, especially experimental and calculated electronic circular dichroism.

Figure 1

COSY and key HMBC correlations of (−)-gambogic acid (1).

Figure 2

Selected NOESY correlations of (−)-gambogic acid (1).

Figure 3

CD spectra of (−)-gambogic acid (1) and (−)-morellic acid (2). The data were obtained in MeOH (0.017 mg/mL for both compounds) on the average of three scans corrected by subtracting a spectrum of the appropriate solution in the absence of the samples recorded under identical conditions. Each scan in the range 200–400 nm was obtained by taking points every 0.5 nm with an integration time of 0.5 sec and a 2 nm band width.