title: Trapping phosphodiester-quinone methide adducts through in situ lactonization.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville 72701, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.forename: K D
authors.initials: KD
authors.lastname: Turnbull
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry*; D000478:Alkylation; D004952:Esters; D006900:Hydroxylation; D045563:Indolequinones; D007211:Indoles / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry*
chemical_list: D000477:Alkylating Agents; D004952:Esters; D045563:Indolequinones; D007211:Indoles; D007783:Lactones; D009943:Organophosphorus Compounds; D011809:Quinones; C068040:quinone methide