Jeannine H. Powell, Edward M. Johnson, P. Gannett
Dec 18, 2000
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Molecules
Abstract
Jeannine H. Powell, Edward M. Johnson II and Peter M. Gannett*Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy,P. O. Box 9530, Morgantown, West Virginia, USA. Tel. (304)-293-1480, Fax (304) 293-2576.*Author to whom correspondence should be addressed; e-mail pgannett@hsc.wvu.eduReceived: 8 May 2000; in revised form 13 November 2000 / Accepted: 14 November 2000 /Published: 18 December 2000Abstract: Methods to reduce the carboxylic acid moiety in 3-carboxy-2,2,5,5-tetramethyl-pyrrolin-1-oxyl to an alcohol as an intermediate toward the corresponding aldehyde havebeen explored and an improved method has been developed.Keywords: Nitroxide, spin label, reduction, carboxylic acid, alcohol, anhydrideIntroductionSpin-labeled nucleic acids have been proposed as probes for the study of DNA conformation anddynamics [1,2]. A potentially very useful moiety is a thymidine analog coupled via an acetylene bridgeto a pyrrolin-N-oxyl molecule [2]. The synthesis of this spin-labeled nucleic acid begins with stablenitroxides described by Rozantsev [3]; further elaboration of these compounds is described in severalsources [2,4]. In our hands, one of the most problematic steps in the overall synthesis is the reductionof the carboxylic acid moiety in 1 to the alcohol 2, which is then oxidized to the aldehyde 3, withoutperturbation of the nitroxide (Figure 1).Here we report several methods we have utilized for theconversion of 1 into 2 and in one instance of 1 into 3.