Methanol → Spongistatin 3

Participants

Reaction Steps

The cell growth inhibitory (P388 leukemia) dichloromethane fraction prepared from a 400 kg (wet wt) scaleup recollection (1988) of Spongia sp conducted in the Republic of Maldives was separated by a series of steric exclusion and partition chromatographic steps employing SEPHADEX LH-20 to obtain P388 active fractions reminiscent of spongistatin 1. A careful HPLC sequence using C-8 SILICA GEL (PREPEX and ULTREMEX) and 1:1 methanol water to 5:5:8 methanol-acetonitrile-water afforded 4.34 mg (1.08×10-6 % yield) of amorphous spongistatin 2: mp 140°-141° C.; [α]D +24.5°,(C 0.39, CH3OH); UV (CH3OH, log ε) λ, 220 (4.21), λ, 273 (2.95) nm; IR (film) 3426, 2937, 1736, 1651, 1603, 1381, 1234, 1177, 1086 cm-1, high resolution FABMS m/z 1227.6040 [M+K]+ corresponding to C63H96O21K (calcd mass 1227.6082). In contrast to that of spongistatin 1, no [M-35]+ ion was found. Spongistatin 3 was also obtained (2.69 mg, 6×10-8 % yield) as a colorless and noncrystalline powder; mp 148°-149° C.; [α]D +28.1° (c 0.15, CH3OH); UV (CH3OH, log ε) λ, 226 (3.14), λ268 (2.24) nm; IR (film) 3426, 2934, 1734, 1653, 1591, 1387, 1231, 1173, 1090 cm-1 ; HRFAB ms, m/z 1219.5556 [M+K]+ corresponding to C61H93ClO20K (calcd mass 1219.5584).

Provenance & Evidence