No abstract

racemase catalysis that made this application of the double isotope fractionation experiment possible. We are also grateful to Dr. W. W. Cleland, who has independently devised and used the double fractionation method, for communicating his work13 prior to publication.

Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at < 10(-6) M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10(-4) M concentrations. An ID50 range of >10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.

Enantioselective epoxidation of allylic alcohols: (2 S ,3 S )‐3‐propyloxiranemethanol product: (2 S ,3 S )‐3‐propyloxiranemethanol

4739for 16 h at reflux under an atmosphere of nitrogen (Dean-Stark apparatus). The solution was cooled and vigorously stirred over anhydrous potassium carbonate for 5 min and then the mixture was filtered and the solvent evaporated to give a pale yellow solid (1.16 g, ca. 100%). Recrystallization from dichloromethane/petroleum ether provided a solid which was identical in all respects with the ether adduct 4f obtained by method 1. 1 1,ll-Dimethyl-10,12-dioxahexacyclo[7.6.1. 16.".02,7.05,15.09.13]-3-beptadecene (12). A solution of the ketal 4g (198 mg, 0.5 mmol, tri-n-butylstannane (320 mg, 1.1 mmol), and azobis(isobutyronitri1e) (2 mg) in toluene (1 mL) was heated for 23 h at reflux under an atmosphere of nitrogen. Carbon tetrachloride (1 mL) was added and refluxing was continued for 2 h. The solution was cooled to ambient temperature and diluted with ether/dichloromethane (2:1, 15 mL). The mixture was treated with a solution of potassium fluoride (2 g) in water (10 mL) and was vigorously stirred for 0.25 h. The suspension of tri-n-butylstannyl fluoride was filtered and the aqueous layer was separated and extracted with ether/dichloromethane (2:1, 10 mL). The organic extracts were washed with 10% aqueous sodium bicarbonate (15 mL), dried (MgSO,), and concentrated. The residue was dissolved in 95% ethanol (5 mL) heated at reflux and sodium metal (805 mg, 35.0 mmol) was added in portions over 1.5 h. More 95% ethanol (2 mL) was added to the thick mixture and refluxing was continued for 2.5 h. The solution was cooled to ambient temperature and poured into ice water (15 mL). The organic material was extracted into petroleum ether (3 X 10 mL), washed with water (10 mL) and saturated sodium chloride solution (10 mL), dried (MgSO,), and evaporated to give a yellow oil (180 mg). Chromatography on neutral alumina (Woelm, activity 1) with dichloromethane/ petroleum ether (1:l) as the eluent afforded the ketal 12: mp 84-86 O C ; IR (CCI,) 3050, 1365, 1375 cm-I; lH NMR (CCI,) 6 6.03 (dd, J = 5 and 2 Hz, 2 H), 1.96 (br s, 2 H), 1.87 and 1.39 (ABq, J = 9 Hz, 8 H), 1.30 (s, 6 H); MS, m / e 258 (M'), 243 (M+ -CH,), M+ -CH, calcd for C17H2202 243.138496, found 243.138077. 1 l-Oxa-2,5-dichlorohexacyclo[7.6.l.l6,13.O2,7.O5~'s.O9~'~]beptadecane (13). To a solution of the ether 4f (1.464 g, 4.0 mmol) in ethyl acetate (40 mL) was added 5% palladium on carbon catalyst (75 mg) and triethylamine (1.01 g, 10 mmol). The mixture was stirred for 3 h at ambient temperature and pressure under a hydrogen atmosphere. The catalyst and triethylamine hydrochloride were removed by filtration through Celite and the filtrate was evaporated to give the dichloro ether 13 (0.957 g, 80%). An analytical sample, mp 98-99 O C , was prepared by sublimation at 90 "C (0.5 mm) ' H NMR (CDCI,) 6 3.52 (s, 4 H), 2.41 (br s, 4 H), 2.29 (s, 4 H), 1.80 (center of a merging ABq, J = 14 Hz, 8 H); MS, m / e 298, 300, 302 (M'). Anal. Calcd for C16H20C120: C, 64.22; H, 6.74. Found: C, 64.47; H , 6.99. 16-0xapentacyclo[8.4.3.O1~1o.O4~1~.O7~12]beptadeca-3,7-diene (14) and 1 l...