A new synthesis of dehydroluciferin [2-(6′-hydroxy-2′-benzothiazolyl)-thiazole-4-carboxylic acid] from 1,4-benzoquinone

A new synthesis of dehydroluciferin [2-(6'-hydroxy-2'-benzothiazolyl)-thiazole-4-carboxylic acid], the oxidative product of luciferin, has been realized starting from 1,4-benzoquinone. Reaction of this compound with L-cysteine ethyl ester, followed by an oxidation-cyclization step afforded 2-carbethoxy-6-hydroxybenzothiazole that was in situ hydrolyzed and decarboxylated to 6-hydroxybenzothiazole. The tert-butyl(dimethyl)silyl ether of this key intermediate was subjected to alpha-lithiation followed by formylation with DMF, and the resulting aldehyde condensed with L-cysteine ethyl ester. Dehydrogenation of the intermediate thiazolidine followed by deprotection afforded dehydroluciferin in 35% overall yield from 1,4-benzoquinone (69% from 6-hydroxybenzothiazole). (C) 2013 Elsevier Ltd. All rights reserved.