Plant antitumor agents. 28. Resolution of a key tricyclic synthon, 5'(RS)-1,5-dioxo-5'-hydroxy-2'H,5'H,6'H-6'-oxopyrano[3',4'-f].DELTA.6,8-tetrahydroindolizine: total synthesis and antitumor activity of 20(S)- and 20(R)-camptothecin
- 1 December 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 30 (12) , 2317-2319
- https://doi.org/10.1021/jm00395a024
Abstract
The resolution of the tricyclic ketone (3a + 3b) by the separation of diastereomeric adducts 4a and 4c of the precursor ketal 5 is described. The regenerated enantiomers 3a and 3b of 100% optical purity represent the key intermediates from which 20(R)-camptothecin (1a) and 20(S)-camptothecin (1b), respectively, have been prepared. The 20R analogue 1a was 10-100 times less active than the natural 20(S)-camptothecin (1b) in 9KB and 9PS cytotoxicity assays and almost inactive in in vivo L-1210 leukemia tests as compared to the highly potent and active natural compound 1b.This publication has 3 references indexed in Scilit:
- Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogsJournal of Medicinal Chemistry, 1986
- Plant antitumor agents. 22. Isolation of 11-hydroxycamptothecin from Camptotheca acuminata decne: total synthesis and biological activityJournal of Medicinal Chemistry, 1986
- Plant antitumor agents. 18. Synthesis and biological activity of camptothecin analogsJournal of Medicinal Chemistry, 1980