New dihydroagarofuranoid sesquiterpenes, a lignan derivative, benzenoid, and antitubercular constituents from the stem of Microtropis japonica

Microtropis japonica (Fr. & Sav.) Hall. f. (Celastraceae) is a small shrub distributed in Japan, Ryukyus, and Taiwan (Lanyu Island and Nanjenshan, Pingtung). Various dihydroagarofuranoid sesquiterpenes [1–3], benzenoids [2,3], and triterpenes [4] are widely distributed in plants of the genus Microtropis. Many of these compounds exhibit cytotoxic [1,4] and antitubercular [2,3] activities. In our studies on the antitubercular constituents of Formosan plants, many species have been screened for in vitro antitubercular activity, and M. japonica has been found to be one of the active species. Investigation of the EtOAc-soluble fraction of the stem of M. japonica has led to the isolation of four new compounds, including two dihydroagarofuranoid sesquiterpenes, 8-benzoyloxymutangin (1) and 15-acetoxyorbiculin G (2), a lignan derivative, 9,9′-O-di-(Z)-feruloyl-(–)-secoisolariciresinol (3), and a benzenoid, 5′-methoxyevofolin B (4), along with 20 known compounds (5–24). Among the known isolates, 3-ethoxy-4-hydroxybenzaldehyde (5) was identified from a natural source for the first time. Salasol A (9) and celahin C (10) are the most effective among the isolates, with MICs of 28.2 and 31.3µM, respectively, against Mycobacterium tuberculosis H₃₇Rv. This paper describes the structural elucidation of 1–5 and the antitubercular activities of the isolates.

Acknowledgement: This work was supported by grant from the National Science Council of the Republic of China.

References: 1. Chen, J. J., et al. (2006)J. Nat. Prod. 69:685–688. 2. Chen, J. J. et al. (2007)J. Nat. Prod. 70:202–205. 3. Chou, T. H. et al. (2007) Chem. Biodivers 4:1594–1600. 4. Chen, I. H. et al. (2006)J. Nat. Prod. 69:1543–1546.