Toward Pyridine-Fused Selenium-Containing Antioxidants 英文参考文献.docVIP

Molecules 2004, 9, 472-479 molecules ISSN 1420-3049 Toward Pyridine-Fused Selenium-Containing Antioxidants Tahli Fenner and Carl H. Schiesser* School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia, 3010. Tel. (+61)-3-8344-4180, Fax (+61)-3-9347-5180. * Author to whom correspondence should be addressed; e-mail: carlhs@.au. Received: 17 February 2004 / Accepted: 21 February 2004 / Published: 31 May 2004 Abstract: Photolysis of the thiohydroximate ester derivative 21 of 2-carboethoxy-2-(2- 2-dodecyl-2- (benzylseleno)pyridin-3-yl)tridecylcarboxylic acid (20) affords carboethoxy-2,3-dihydroselenolo[2,3-b]pyridine (22) in 89% yield in a process presumably involving intramolecular homolytic substitution by a tertiary alkyl radical at selenium with loss of a benzyl radical. Work toward extending this methodology to the preparation of pyridine-fused selenium analogues of antioxidants is described. Keywords: Free radical, homolytic substitution, selenium, antioxidants. Introduction Interest in selenium containing therapeutics has grown over the last thirty years [1]. Simple organoselenium compounds have been prepared, such as selenazolopyrimidone (1), that show antitumor activity against mouse leukemia [2]. (Aminoethyl)phenylselenide (2) shows excellent antihypertensive activity and selenazine derivatives such as 3 show both antibacterial and antitumor activity [3]. Despite this, the major therapeutic benefit that selenium currently offers appears to be in the form of dietary supplements [4]. Selenium is an essential trace element and dietary deficiency can lead to ailments including gum disease, as well as debilitating conditions such as Keshan’s disease [4e]. The biochemistry and pharmacology of selenium is of intense current interest. Selenium is now know to be intimately involved in the activi