Trapping phosphodiester-quinone methide adducts through in situ lactonization
by Zhou, Q. B.; Turnbull, K. D.
The goal of in situ modification of DNA via phosphodiester alkylation has led to our design of quinone methide derivatives capable of alkylating dialkyl phosphates. A series of catechol derivatives were investigated to trap the phosphodiester-quinone methide alkylation adduct through in situ lactonization. The catechol derivatives were uniquely capable of characterizable p-quinone methide formation for mechanistic clarity. These investigations revealed that with a highly reactive lactonization group (phenyl ester), lactonization competed with quinone methide formation. Lactone-forming groups of lower reactivity (methyl ester, n-propyl ester, and dimethyl amide) allowed quinone methide formation followed by phosphodiester alkylation; however, they were ineffective at in situ lactonization to drain the phosphodiester alkylation equilibrium to the desired phosphotriester product. The derivatives tethered with lactone-forming functionality of intermediate reactivity (chloro-, trichloro-, and trifluoroethyl esters), allowed quinone methide formation, phosphodiester alkylation, and in situ lactonization to efficiently afford the trapped phosphotriester adduct.
- Journal
- Journal of Organic Chemistry
- Volume
- 65
- Issue
- 7
- Year
- 2000
- Start Page
- 2022-2029
- URL
- https://dx.doi.org/10.1021/jo9915168
- ISBN/ISSN
- 1520-6904; 0022-3263
- DOI
- 10.1021/jo9915168