Simple and efficient preparation of [10,20-C-13(2)]- and [10-CH3,13-C-13(2)]-10-methylretinal: Introduction of Substituents at the 2-position of 2,3-unsaturated nitriles

In this paper, we present the synthesis of [10,20-C-13(2)] -10-methylretina l and [10-CH3,13-C-13(2)] -10-methylretinal, two doubly C-13-labeled chemic ally modified retinals that have been recently used to study the structural and functional details behind the photocascade of bovine rhodopsin (Verdeg em et al. Biochemistry 1999, 38, 11316; de Lange et al. Biochemistry 1998, 37, 1411). To obtain both doubly C-13-labeled compounds, we developed a nov el synthetic method to directly and regiospecifically introduce a methyl su bstituent on the 2-position of 3-methyl-5-(2',6',6'-trimethyl-1'cyclohexen- 1'-yl)-2,4-pentadienenitrile. Encouraged by these results, we investigated the scope of this novel reaction by developing a general method for the int roduction of a variety of substituents to the 2-position of 3-methyl-2,3-un saturated nitriles, paving the way for simple and efficient synthesis of a wide variety of 10-, 14-, and 10,14-substituted chemically modified retinal s, and other biologically important compounds.