Four analogues, 10-methoxy (20), 12-aza (29), benz[j] (36), and 18-methoxy (38), of camptothecin were obtained by total synthesis. The two water-soluble analogues, 10-[(carboxymethyl)oxy]- (24) and 10-[2'-(diethylamino)-ethoxy]-20(S)-camptothecin (26), with intact ring E were prepared from natural 10 hydroxycamptothecin (3). In general, there was a good correlation between in vitro 9KB cytotoxicity and activity in the P-388 leukemia system. While the aza analogue 29 was active in P-388 only at a much higher dose level than natural camptothecin (1), the 18-methoxy analogue 38 exhibited activity comparable to that of 1. The water-soluble derivative 24 was inactive. The amine hydrochloride 26 showed excellent activity at a high dose level. This could be due to its hydrolysis to 3. dl-Camptothecin (17) was roughly half as active as 1, indicating that the l isomer is inactive.

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Improvements in the Separation of /3-Carotene and Lycopene by Column ChromatographyAn excellent experiment for demonstrating column chromatography is the separation of /3-carotene and lycopene in carrot and tomato paste, respectively. The following is a modification of the experiment as written in Fieser and Williams.1 Three grams each of carrot and tomato paste were placed in a beaker with 15 mL of 95% ethanol.2 The mixture was well stirred with a glass rod for several minutes and filtered using vacuum filtration, and the residue was pressed with another piece of filter paper to get out as much liquid as possible. The alcohol extract was discarded and the dehydrated residue was placed in a 50-mL flask along with 10 mL of dichloromethane.3 The mixture was refluxed for 5 min and then filtered using vacuum filtration. The residue was returned to the flask and the procedure was repeated twice more. The dichloromethane extracts were combined, washed once with saturated sodium chloride solution, dried over sodium sulfate, and evaporated to dryness. The oily residue was taken up in 2 mL of low-hoiling petroleum ether.4 A 150 X 11-mm column of activity I alumina was prepared using low-boiling petroleum ether. The carotanoid mixture was applied to the alumina column in a narrow band using petroleum ether to wash down the sides of the column. After several milliliters of petroleum ether were passed through the column (the carotanoids should remain in a narrow band at the top of the column), the solvent was changed to 10% diethyl ether-petroleum ether. The /3-carotene separated as a distinct yellow band from the orange lycopene. Once all the /3-carotene was eluted off, the solvent was switched to 50% diethyl ether-petroleum ether in order to elute off the lycopene. The solvent was evaporated from the two fractions and approximately 0.2 mL of dichloromethane was added to each residue. Thin-layer chromatography was done using silica gel plates and 5% chloroform-cyclohexane as the eluting solvent. The /3-carotene gave a distinct yellow spot with an Rf of 0.4, and lycopene gave an orange spot with an /?f of 0.2. This experiment requires about 3.5 h.

signal above 2.4 ppm; mass spectrum m/e 460 (M+), 445 (M+ -CHS), 432 (M+ -CO), 400 (M+ -COS), 316 (M+ -144).

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