Hydrides reductive deamination

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

Thiochroman-4-ones are reduced to thiochroman-4-ols by sodium borohydride6 and lithium aluminum hydride.50 Lithium aluminum hydride reduction of thiofiavan-4-ones (27) forms the 2,4-ws-thiofiavan-4-ols (28) as in Eq. (8). By contrast, deamination of 2,4-cis-4-aminothio-flavans (29) with nitrous acid produced the trans- alcohol (30) as shown in Eq. (9).50 The alcohols obtained by the hydride reductions have... 

Chemically, methods for deoxygenation and reductive deamination have seen additions in the last two decades which depart from those traditional approaches using hydride reduction of activated alcohols and diazene generation from aliphatic amines. New methods for amine activation, new complex hydrides and, in particular, methods using electron transfer and free radical processes have greatly expanded the range of substrate molecules which can be subject to efficient functional group removal. 

An overall reductive deamination procedure for the conversion of a-amino-acid esters [R CH(NH2)C02R ] into esters (R CH2C02R ) involves prior conversion of the former into the a-isonitrilo-ester, followed by reduction with tributyltin hydride overall yields are very good. ... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

The deamination of primary amines RNH2 (R = CsHn, PhCH2, PhCHMe or PhCH=CHCH2) to the corresponding hydrocarbons is accomplished by conversion into the benzimidoyl chlorides, followed by reduction with tributyltin hydride in the presence of AIBN (equation 121)398. 

Deamination of e,nwith sodium nitrite in acetic acid/sodium acetate gave a mixture of compounds from which, after reduction of the crude mixture with lithium aluminum hydride, was isolated bicyclo[3.1.1]heptanediol 23 in 20% yield by chromatography.88,89... 

Hydrodeamination.6 ct-Amino acid esters can be deaminated by conversion to isonitrile esters followed by reduction with this hydride (equation 1). 

Amino-3-cyanobenzodiazepinium chloride reacted with sodium boro-hydride to give a mixture of 2,3-dihydro- and 2,3,4,5-tetrahydro-3-cyano-benzodiazepines. It was suggested that deamination, brought about by hydride attack at C-2, preceded reduction (81CPB1165). Similar reduction of the 2-amino-3-ethoxycarbonyl analog provided only 3-ethoxycarbonyl-2,3-dihydrobenzodiazepine. 

DAAO is one of the most extensively studied flavoprotein oxidases. The homodimeric enzyme catalyzes the strictly stere-ospecihc oxidative deamination of neutral and hydrophobic D-amino acids to give a-keto acids and ammonia (Fig. 3a). In the reductive half-reaction the D-amino acid substrate is converted to the imino acid product via hydride transfer (21). During the oxidative half-reaction, the imino acid is released and hydrolyzed. Mammalian and yeast DAAO share the same catalytic mechanism, but they differ in kinetic mechanism, catalytic efficiency, substrate specificity, and protein stability. The dimeric structures of the mammalian enzymes show a head-to-head mode of monomer-monomer interaction, which is different from the head-to-tail mode of dimerization observed in Rhodotorula gracilis DAAO (20). Benzoate is a potent competitive inhibitor of mammalian DAAO. Binding of this ligand strengthens the apoenzyme-flavin interaction and increases the conformational stability of the porcine enzyme. 

Deamination of an amine can be accomplished by reduction of the aryidiazonium tetrafluoroborate with zinc and ethanol " or, more elFectively, with sodium boro-hydride (8)." The simplest procedure is to the solid borohydride in portions to... 

Equation (24) has been chosen as an example of the radical deoxygenation of secondary alcohols via thiono esters [58], whereas Eq. (25) represents an example of deamination of primary amines via isocyanides [7, 54]. The reaction mechanism of these reductions is similar to that described for tin hydride, i.e. attack of silyl radical on the C=S or N=C moieties to form a radical intermediate which undergoes -scission to form alkyl radicals. Hydrogen abstraction from the hydride gives the product and the (TMS)3Si radical, thus completing the cycle of this chain reaction. 

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