Asymmetric reduction of methyl benzoylformate with a chiral NAD(P)H-model compound

Ohno, Atsuyoshi; Ikeguchi, Masahiko; Kimura, Takeshi; Oka, Shinzaburo

doi:10.1039/c39780000328

Cited by 29 publications

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“…119−128 The role played by a divalent metal ion such as magnesium may be the activation of the substrate and the 1,4-dihydronicotinamide, as well as the stabilization of the transition state. 129,130 mNADHs, especially MNAH, PNAH, and BNAH, have been used in the reduction of a wide range of compounds (Scheme 14), such as α-keto esters, 121,131,132 α-diketones, 133 α-hydroxy ketones, 133 trifluoroacetophenone, 134,135 benzaldehydes and acetophenone, 136 2-acylpyridines, 137 and cinnamoylpyridines (with Mg 2+ or Zn 2+ ). 138 The reduction of different imines to amines has also been carried out, with α-imino esters, 139 αimino acids, 140 α,β-unsaturated iminium salts, 141 and reductive aminations.…”

Section: Applications To Organic Chemistrymentioning

confidence: 99%

“…mNADHs, especially MNAH, PNAH, and BNAH, have been used in the reduction of a wide range of compounds (Scheme ), such as α-keto esters, ,, α-diketones, α-hydroxy ketones, trifluoroacetophenone, , benzaldehydes and acetophenone, 2-acylpyridines, and cinnamoylpyridines (with Mg 2+ or Zn 2+ ) . The reduction of different imines to amines has also been carried out, with α-imino esters, α-imino acids, α,β-unsaturated iminium salts, and reductive aminations .…”

Section: Applications To Organic Chemistrymentioning

confidence: 99%

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Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry

2014

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The topic of synthetic nicotinamide cofactor analogues is resurfacing as new approaches are being explored, especially in the areas of organic chemistry and biocatalysis. By changing the adenine dinucleotide moiety for a simpler alkyl or aryl group and taking advantage of their ability for hydride transfer, these cofactor biomimetics are used in redox reactions in catalytic or stoichiometric amounts. Alteration of the amide functional group on the pyridine ring, thus varying their electronic properties, and the presence of divalent metal ions also enable rate acceleration in enzyme-catalyzed and chemical reactions. Herein, an overview of the synthesis, mechanism, and applications of nicotinamide cofactor NAD(P)H analogues in redox chemistry, particularly 1,4-dihydronicotinamide derivatives and their oxidized counterpart, is presented. These compounds have been extensively studied as models of NAD(P)H for enzymatic reactions with oxidoreductases as well as nonenzymatic reactions, and the focus of this review is placed mainly on the scope and limitations of these synthetic analogues in biocatalysis.

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Section: Applications To Organic Chemistrymentioning

confidence: 99%

Section: Applications To Organic Chemistrymentioning

confidence: 99%

Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry

2014

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“…For this reason, chiral NAD(P)H model 21 was designed by Ohno's group (Figure 11). 46,47 It was found that 21 exerts high enantiospecificity in the reaction in the presence of Mg 2+ , and the ee was controlled by steric effects of substituents. The C-4 functional group played a crucial role in the transition state.…”

Section: Effect Of the C-4 Substituent Of Dihydropyridinementioning

confidence: 99%

Progress on Chiral NAD(P)H Model Compounds

Chen

Wang

Xing

et al. 2016

Synlett

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NAD(P)H and NAD + have a significant role in biochemistry, and many NAD(P)H models received particular attention. Research in NADH models mainly focuses on asymmetric reduction and life sciences. Over the past few decades, a particularly large number of new chiral NAD(P)H models have appeared, and there have been significant developments in this area. We summarized advanced research in chiral NAD(P)H models in this paper. These models not only show very good performance in asymmetric reduction, but also have excellent fluorescence features. In addition, we present a discussion about some recent studies on the asymmetric reduction of NAD(P)H-dependent dehydrogenase, and we open a new door on research into NAD(P)H models. At last, some advances focused on the fluorescence phenomenon of some chiral NAD(P)H models have also been summarized.

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“…[2] The second aspect was to incorporate a substituent at the reaction center: the C-4 position of the dihydropyridine ring. [3] The third one was to design the specific conformation to obtain high stereoselectivity. [4] However, in the first situation the dihydronicotinamide unit needs to be modified significantly by introducing big chiral auxiliaries, a complicated ring or by changing the amide group to a chiral sulfinyl group.…”

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confidence: 99%

A Novel NADH Model: Design, Synthesis, and its Chiral Reduction and Fluorescent Emission

Wang¹,

Zhao²

2009

Adv Synth Catal

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A novel chiral nicotinamide adenine dinucleotide hydrogen (NADH) model with C 3 symmetry was designed and synthesized. Hydrogens at the C-4 position of all dihydropyridine rings in the inner part of the bowl could transfer to the substrate with powerful enantioselectivity. This novel C 3 symmetrical NADH model is capable of fluorescence emission at 455 nm when excited at 390 nm.Keywords: chiral NADH model; enantioselectivity; fluorescence; magnesium(II); synthesis The coenzyme nicotinamide adenine dinucleotide hydrogen (NADH) is an important molecule in nature. Over the past several decades, NADH mimics have become one of the highlights of biochemistry and organic chemistry.[1] To the best of our knowledge, the dihydropyridine amido group is the key structure for NADH models.Kanomata [1f] designed and synthesized a bridged NADH model with an [n]A C H T U N G T R E N N U N G (2,5)pyridinophane (parapyridinophane) skeleton as a sterically-demanding side chain that induces high enantioselectivity. Kanomata believed that the oligomethylene chain bridging the 2-and 5-positions of a dihydronicotinoyl ring would behave as an "enzyme wall" that allows the substrates to approach from the opposite side exclusively. In the asymmetric reduction of methyl benzoylformate, mandelate was obtained with a high enantiomeric excess when a 1 molar ratio of magnesium was used.Generally, chemists had formerly designed NADH models according to three aspects: the first one was to control the stereoselectivity by changing the substitutent of the dihydronicotinamide with a view to form a remote sterically-demanding side chain.[2] The second aspect was to incorporate a substituent at the reaction center: the C-4 position of the dihydropyridine ring.[3] The third one was to design the specific conformation to obtain high stereoselectivity.[4] However, in the first situation the dihydronicotinamide unit needs to be modified significantly by introducing big chiral auxiliaries, a complicated ring or by changing the amide group to a chiral sulfinyl group. The second one suffered from loss of chirality at the C-4 position during the course of the model reduction reaction. The third one was particular and by far fewer models have been studied. Herein, a novel chiral NADH model compound 1 with C 3 -symmetry was designed and synthesized.Our model 1 has six chiral carbon centers. (1R,2R)-Diaminocyclohexane is introduced as chiral source to connect three identical pyridine-3,5-dicarbonyl groups into a large ring. Then three identical 1,4-dihydropyridine units are connected by the phenyl-1,3,5-trimethylene group to form model 1. Molecular modeling via molecular dynamics followed by energy minimization with Gaussian 03 shows that the bowl-shaped conformation shown in Figure 1 is the most stable one. The phenyl-1,3,5-trimethylene group is the "bottom" of the "bowl" and the rigidly defined concave cavity of the bowl can hold a metal ion in a fixed position relative to the 1,4-dihydropyridine. As a result, regulation of the stereoselective appro...

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Asymmetric reduction of methyl benzoylformate with a chiral NAD(P)H-model compound

Abstract: The title reaction with N-(R)-a-methylbenzyl-1-propyl-2-methyl-4-(R) -methyl-1,4-dihydronicotinarnide or its 4-(S)-methyl isomer affords methyl mandelate in 97 yo optical yield and quantitative chemical yield.

Cited by 29 publications

References 0 publications

Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry

Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry

Progress on Chiral NAD(P)H Model Compounds

A Novel NADH Model: Design, Synthesis, and its Chiral Reduction and Fluorescent Emission

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