20-O-Acylcamptothecin Derivatives: Evidence for Lactone Stabilization
- 28 June 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 65 (15) , 4601-4606
- https://doi.org/10.1021/jo000221n
Abstract
Convincing UV and NMR spectrophotometric evidence is presented which demonstrates that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are substantially more stable in the lactone form than the 20-OH parent. Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O-ether derivative of CPT underwent endocyclic ring opening at pH ≥ 8.5, while the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl PEG (or alkyl) carboxylate forms.Keywords
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