Regioselective Reduction of NAD+ Models with [Cp*Rh(bpy)H]+: Structure-Activity Relationships and Mechanistic Aspects in the Formation of the 1,4-NADH Derivatives (original) (raw)

1999, Angewandte Chemie International Edition

The interest in practical methods for the regeneration of the co-enzyme 1,4-NADH, the reduced form of nicotinamide adenine dinucleotide (NAD ), has continued to be high in the field of biocatalysis, where enzymatic reduction reactions are important for the synthesis of chiral organic compounds. [1a, b] Conversion of NAD into 1,4-NADH by enzymatic, chemical, photochemical, and electrochemical methods has been studied extensively in order to increase the rate of the regeneration, while maintaining the necessary high regioselectivity. The regeneration is frequently the limiting step in the eventual use of 1,4-NADH in enzymatic synthesis, particularly for higher volume and more energy intensive processes. [1a, b] In the search for higher rates and a more economical regeneration process various transition metal hydrides have been studied as catalysts for the regioselective reduction of NAD and NAD models to their corresponding 1,4-NADH derivatives. [2a±g] In the most successful example, Steckhan and co-workers have described the use of [Cp*Rh(bpy)(H)] (Cp* pentamethylcyclopentadienyl, bpy 2,2'-bipyridyl), generated in situ, for the regiospecific reduction of NAD to 1,4-NADH, [2b] and then demonstrated the cofactor regeneration process in enzymatic, chiral reduction reactions. [3, 4] While the above mentioned reduction of NAD by [Cp*Rh(bpy)H] was shown to be regiospecific for 1,4-NADH, [2b, 5a] the full mechanistic details of this important 8.1 Hz, 4 F), À 162.35 (dt, 1 J 23.03, 2 J 6.9 Hz, 2 F); HR-MS: m/z: 797.0854 (calcd for C 37 H 12 N 4 F 15 : 797.0822). nm (9.3); 1 H NMR (CDCl 3 ): d 8.91 (d, J 4.2 Hz, 2 H), 8.49 (d, J 4.8 Hz, 2 H), 8.35 (d J 4.6 Hz, 4 H), 7.72 (m, 3 H), 7.33 (m, 6 H), À 1.7 (br s, 3 H); HR-MS: m/z: 729.9810 (calcd for C 37 H 20 N 4 Cl 6 : 729.9819).