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• 作者：H. Christine Lo ; Carmen Leiva ; Olivier Buriez ; John B. Kerr ; Marilyn M. Olmstead ; and Richard H. Fish
• 刊名：Inorganic Chemistry
• 出版年：2001
• 出版时间：December 17, 2001
• 年：2001
• 卷：40
• 期：26
• 页码：6705 - 6716
• 全文大小：182K
• 年卷期：v.40,no.26(December 17, 2001)
• ISSN：1520-510X

文摘

Cofactor regeneration; i.e., regiospecific conversion of NAD⁺ to 1,4-NADH, has been extensively studied and isa crucial component in the eventual use of 1,4-NADH in a variety of bioorganic synthesis processes involvingthe formation of chiral organic compounds. We have studied the reduction of a model NAD⁺ compound,1-benzylnicotinamide triflate, 1a, using [Cp*Rh(bpy)(H₂O)]²⁺, 2 (Cp* = ⁵-C₅Me₅, bpy = 2,2'-bipyridyl), as thecatalyst precursor and sodium formate (HCO₂Na) as the hydride source in 1:1 H₂O/THF and have found exclusive1-benzyl-1,4-dihydronicotinamide regioselectivity, as was observed previously for natural NAD⁺ that provided1,4-NADH (see: Steckhan et al. Organometallics 1991, 10, 1568). Moreover, a variety of 3-substituted derivativesof 1-benzylpyridinium triflate, in addition to the -C(O)NH₂ group (1a), were also studied to ascertain that this3-functionality (e.g., -C(O)NHCH₃, -C(S)NH₂, -C(O)CH₃, -C(O)OCH₃, and -CN, 1b,d-g) coordinates to a[Cp*Rh(bpy)H]⁺ complex to direct the concerted, regioselective transfer of the hydride group from the rhodiumto the 4-ring position of the NAD⁺ model; all coordinating 3-substituents had relative rates in the 0.9-1.3 rangewith substrate 1a set to 1.0. If in fact the 3-substituent presented a steric effect [-C(O)NH(CH₂CH₃)₂, 1c] or wasa nonbinding group (-CH₃, 1h; -H, 1i), no catalytic hydride transfer was observed even with the more electrophilic2 and 6 ring positions being readily available, which further implicated the crucial coordination of the NAD⁺model to the Cp*Rh metal ion center. We also found that the 1-benzyl substituent on the nitrogen atom exerteda substantial electron-withdrawing effect, in comparison to the electron-donating 1-methyl substituent, and favorablyaffected the rate of the regioselective reduction (rate enhancement of 1-benzyl/1-methyl = 2.0). The kinetics ofthe regioselective reduction of 1a were studied to show that the initial rate of reduction, r_i, is affected by theconcentrations of the substrate, 1a, precatalyst, 2, and the hydride source, HCO₂Na, in 1:1 H₂O/THF: d[1-benzyl-1,4-dihydronicotnamide]/dt = k_cat[1a][2][HCO₂Na]. Furthermore, we wish to demonstrate that a previouslysynthesized aqueous NAD⁺ model, -nicotinamide ribose-5'-methyl phosphate, 3, shows a similar regioselectivityfor the 1,4-NADH analogue, while the initial rate (r_i) for the regioselective reduction of 3 and NAD⁺ itself wasfound to be comparable in water but faster by a factor of ~3 in comparison to 1a in 1:1 H₂O/THF; the solvent,THF, appeared to inhibit the rate of reduction in 1a by presumably competing with the substrate 1a for theCp*Rh metal ion center. However, in H₂O, the initial kinetic rate for substrate 3 was not affected by its concentrationand implies that, in H₂O, [Cp*Rh(bpy)H]⁺ formation is rate determining. We assume that binding of 3 and NAD⁺to the Cp*Rh metal ion center is also a pertinent step for 1,4-dihydro product formation, the experimental rateexpression in H₂O being d[1,4-dihydro--nicotinamide ribose-5'-methyl phosphate]/dt = k_cat[2][HCO₂Na]. Whatwe have discovered, for the first time, is evidence that the regioselective reduction of NAD⁺ to 1,4-NADH by[Cp*Rh(bpy)H]⁺ is a consequence of the amide's ability to coordinate to the Cp*Rh metal center, therebyconstricting the kinetically favorable six-membered ring transition state for plausible concerted hydride transfer/insertion to C4 to regioselectively provide the 1,4-NADH derivative; [Cp*Rh(bpy)H]⁺ can be categorized as abiomimetic enzymatic hydride via its ability to bind and regioselectively transfer hydride to C4, exclusively.Clearly, the pyrophosphate and adenosine groups associated with the structure of NAD⁺ are not essential in therate of hydride transfer to C4, with NAD⁺ model 3 having a similar initial rate (r_i) of reduction as NAD⁺ itselfin water. Finally, a catalytic cycle will be proposed to account for our overall observations.