Silane Reduction of 5-Hydroxy-6-methyl-pyridine-3,4-dicarboxylic Acid Diethyl Ester Synthesis of Vitamin B6 英文参考文献.docVIP

Molecules 2003, 8, 873-881 molecules ISSN 1420-3049 Silane Reduction of 5-Hydroxy-6-methyl-pyridine-3,4- dicarboxylic Acid Diethyl Ester: Synthesis of Vitamin B6 Yves René Dumond and Andrew G. Gum* DSM Nutritional Products§ RD Chemical Process Technology, P.O. Box 3255, Bldg. 214/0.61, CH- 4002 Basel, Switzerland, Tel. (+41) 61 687 3293, Fax (+41) 61 687 2117. * Author to whom correspondence should be addressed; email: andrew.gum@. § registered as Roche Vitamins Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland Received: 31 October 2003; in revised form: 1 December 2003 / Accepted: 10 December 2003/ Published: 31 December 2003 Abstract: Alternative methods for the synthesis of pyridoxine have been investigated. The key intermediate, 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5), was reduced with either a silane monomer (MeSiH(OEt)2) or a polysiloxane (polymethylhydrosiloxane, PMHS) to afford crude pyridoxine. An isolation technique utilizing a commercially available resin was devised, affording the desired product, vitamin B6, in an overall yield of 38-54 % and a purity of 76%. Keywords: Polymethylhydrosiloxane (PMHS), silanes, ester reduction, pyridoxine, vitamin B6 Introduction Vitamin B6 is a water-soluble vitamin that is manufactured in bulk as pyridoxine hydrochloride. Vitamin B6 is an important nutrient and plays an essential role in the bodys amino acid biochemical pathways. As a consequence, it is found in a variety of vitamin preparations and is a common food additive. Because of its importance, the synthesis and commercial production of vitamin B6 have been the subject of intense research for many years [1-2]. Currently, the preferred industrial synthesis of vitamin B6 uses the Kondrat’eva approach [3-6], which combines a Diels-Alder reaction with a subsequent aromatization as the key step in forming the hydroxypyridine ring. Typically, the Diels-  Molec