Continuation of the phytochemical examination of this plant (1) which has produced two antitumor principles, vincaleukoblastine and leurosine, has yielded six previously unreported minor alkaloids in addition to those already reported from these laboratories (2). Details of the procedure leading to the preparation of isoleurosine, lochneridine, sitsirikine sulfate, vincamicine, Catharine, and vindolicine, as well as their preliminary characterization, are described.
HE EXPERIMENTAL antitumor activity of Tvincaleukoblastine (VLB)' and leurosine against the P-1534 leukemia, as well as against some other transplantable neoplasms, has been reported by Johnson, Wright, Svoboda, Vlantis, and M a t t s (3-6) and by Noble, Beer, and Cutts (7-13). The antimitotic activity of VLB in tissue culture has been studied by Palmer, Livengood, Warren, Simpson, and Johnson (14). The activity of these compounds in markedly inhibiting the growth of a heterologously transplanted human choriocarcinoma in the hamster cheek pouch has been shown by Hertz (1 5). Reports on preliminary clinical trials of VLB2 have been presented by Hodes, Rohn, and Bond (16-19), Hertz, Lipsett, and Moy (20-22), and Warwick, Darte, and Brown (23, 24).
In addition to the 12 crystalline alkaloids already obtained from this plant in our laboratories (2)3 continued investigation has resulted in the preparation of six new minor alkaloids. Reworking of the previously described A and B alkaloidal fractions enabled us to obtain isoleurosine and lochneridine from the former and sitsirikine sulfate and vincamicine from the latter. Vindolicine and Catharine were obtained by a different procedure involving a gradient pH extraction. Alkaloids from the benzene extraction of alkalinized ammonium hydroxide drug were extracted by a dilute tartaric acid solution. The pH of this extract was adjusted to 3.3 and extracted