Concise total syntheses of dl-camptothecin and related anticancer drugs Journal Article

  


Authors: Shen, W.; Coburn, C. A.; Bornmann, W. G.; Danishefsky, S. J.
Article Title: Concise total syntheses of dl-camptothecin and related anticancer drugs
Abstract: The readily available tricyclic ester 10 has been converted to dl-camptothecin (1) in 39% yield. It was discovered that, with the C5 carbomethoxy group in place, the C6 benzylic position of 10 (pyridone numbering) is selectively deprotonated by sodium hexamethyldisilazide. This allows for condensation with benzaldehyde to produce acid 17 which, after ozonolysis and methylation, afforded the tricyclic keto ester 16. The latter is smoothly converted to camptothecin (1), 10-hydroxycamptothecin (24), and 7-ethyl-10-hydroxycamptothecin (31) via (i) Friedländer condensation with appropriate aminobenzaldehydes, (ii) HBr-induced decarbomethoxylation, and (iii) hydroxylation at C20. In the case of the two analog syntheses, the HBr step also accomplishes concurrent demethylation of the C10 methoxyl group. © 1993, American Chemical Society. All rights reserved.
Keywords: antineoplastic agent; 7 ethyl 10 hydroxycamptothecin; camptothecin; drug synthesis; camptothecin derivative; reaction analysis; 10 hydroxycamptothecin; article
Journal Title: Journal of Organic Chemistry
Volume: 58
Issue: 3
ISSN: 0022-3263
Publisher: American Chemical Society  
Date Published: 1993-01-01
Start Page: 611
End Page: 617
Language: English
DOI: 10.1021/jo00055a012
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027394922&doi=10.1021%2fjo00055a012&partnerID=40&md5=d8f9f014906de0e503229f7435059770
Notes: Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. William Bornmann
    112 Bornmann
  2. Samuel J Danishefsky
    539 Danishefsky
Related MSK Work