Isolation and synthesis of two antiproliferative calamenene-type sesquiterpenoids from Sterculia tavia from the Madagascar rain forest

Abstract

Investigation of the endemic Madagascan plant Sterculia taiva Baill. (Malvaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of two new bioactive calamenene-type sesquiterpenoids, named tavinin A (2) and epi-tavinin A (3) together with the known sesquiterpenoid mansonone G (1). The structures of the two new compounds were elucidated based on analysis of their 1D and 2D NMR spectra and mass spectrometric data, and were confirmed by de novo synthesis. The three isolated sesquiterpenoids (1-3) had modest antiproliferative activities against the A2780 ovarian cancer cell line, with IC(50) values of 10.2, 5.5 and 6.7 μM, respectively.

Figure 1

a. HMBC, COSY, and NOESY correlations of 2; b. HMBC, COSY and NOESY correlations of 3

Scheme 1

Conditions: a. Isopropylmagnesium chloride, THF, −15 °C, 1h, 42.1%; b. 2% Osmium tetroxide, N-Methyl-morpholine-N-oxide (NMO), dichloromethane, RT, 48h, 75.4%; c. Sulfur trioxide-pyridine complex, dichloromethane, 0 °C, 2h, 91.9%; d. 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), benzene, reflux, 24h, 58%; e. NaBH₄, CeCl₃.7H₂O, rt, 5min, 90.3%. f. 2% Osmium tetroxide, N-Methyl-morpholine-N-oxide (NMO), dichloromethane, RT, 48 h; g. Sulfur trioxide-pyridine complex, dichloromethane, 0°C, 2 h, 13% (rac-2) 10% (rac-3). Synthesis of compound 2 and 3