Reduction by borohydrides

Enzymes can also undergo other side reactions under conditions that divert a chemically reactive intermediate from its usual catalytic function. Again, glutamine synthetase is an excellent example (see figure above), because its side reactions include acyl-phosphate reduction by borohydride, pyroglutamate formation, and the formation of y-glutamyl hydroxamate in the presence of hydroxylamine and arsenate. 

Reduction, by borohydride, of the polyaldehyde to the polyalcohol, followed by complete hydrolysis by acid gives glycolaldehyde (4), glyceritol... 

If a true equilibrium exists between the two forms, the shift must be very slow since extended times of reduction by borohydride do not improve the yield significantly. 

Mechanistic details involved in imine and carbonyP - reductions are undoubtedly similar, although thorough investigations of the former are lacking. Certainly, hydride transfer to the electrophilic carbon, with or without prior activation by protonation or complexation is essential for both types of ir-systems (Scheme 1). Whether or not alcohol solvents participate in imine reductions by borohydride (in the absence of added acid) to furnish the amine proton (as is the case with carbonyls) is not known and must await detailed kinetic study and analysis of the initial intermediates formed before hydrolysis. Direct, in situ, reductive amination with NaBHsCN has been attributed to initial, reversible formation (via an intermediate hydroxyamine, (1) of an iminium ion (2) from carbonyls and amines followed by rapid attack by hydride (Scheme 2). However, the inermess of an imine (partial structure 3) to the usual reductive... 

Fuhrhop et al.35 demonstrated that incorporation of quinone moieties into either the head groups or within the hydrophobic spacer of a bolaphile gave redox-active membranes (Figure 9). Unsymmetrical bo-laamphiphiles were used as models for photosynthetic electron acceptors (e.g. 29) and vesicle formation was verified by electron micrograph. The anticipated membrane organization would position the quinone moieties on the vesicle exterior. The location of the quinone moieties in this series was verified by their quantitative reduction by borohydride. Since boro-hydride does not diffuse through lipid membranes these membrane quinones must be part of the vesicle exterior. 

In protic media, it is the solvent that plays the role of the acid catalyst and provides electrophilic assistance by hydrogen bonding [ESI, PSl, W2], In alcoholic media, it has been shown that the transition state for the reduction by borohydrides involves an alcohol molecule that is converted to the corresponding borate (Figure 3.2). 

The keto-amide (25 R = OMe), on treatment with PPA, gives only the oxazole (24), but it can be converted into the 3-benzazepine (26) via reduction (by borohydride) to the alcohol followed by cyclization with PPA. ... 

Reactions of 1,3-Diazepines. The 1,3-diazepine system (96) was found to be very susceptible to decomposition by water, acids, silica gel, and alumina, and could only be isolated via chromatography on Sephadex. Hydrolysis at ca 50 °C gave (95) and photolysis gave (97). The hydrolysis, photolysis, and reduction by borohydride of the thieno-fused analogues (98) and (99) were also investigated... 

The two versions of the Miilheim electrochemical process provide colloidal solutions (e.g., in THF) of a variety of transition metal or bimetallic nanoparticles, and constitute a simple, clean and reliable alternative to chemical processes such as reduction by borohydrides in which the excess reducing agent and/or the oxidized form thereof have to be removed from the product (in fact, boron originating from boron hydrides is sometimes incorporated in the nanopaiticles) [26], But are these methods of any use in catalysis. One possibiUty is immobUization on soUd carriers, deUvering materials having islands of metal clusters of a predefined size. Moreover, they allow for the design of heterogeneous catalysts with well-defined compositional and structural features on a macroscopic and microscopic level. 

In the transamination process, the pyridoxal coenzyme is transferred from the enzyme-imine intermediate to the substrate-imine. The evidence of an imine function comes from reduction by borohydride which does not yield pyridoxine but shows that a covalent bond is formed with a lysine residue of the enzyme. The protonation of the pyridine ring is also essential for catalysis. 

This enzyme catalyses the decarboxylation of the ) -ketoacid oxaloacetate, with the same stoichiometry as acetoacetate decarboxylase. The former however, requires a Mn ion for activity and is insensitive to the action of sodium borohydride. This duality of mechanism is not unlike the one observed for enzymatic aldol condensation, where enzymes of Class 1 react by forming Schiff-base intermediates, whereas enzymes of Class II show metal ion requirements [47]. Oxaloacetate decarboxylase from cod also catalyses the reduction by borohydride of the enzymatic reaction product pyruvate. This is evidenced by the accumulation of D-lactate in presence of enzyme, reducing agent, and manganous ions. It has been proposed that both reduction and decarboxylation occur by way of an enzyme-metal ion-substrate complex in which the metal ion acts as an electron sink, thereby stabilizing the enolate ion formed in the decarboxylation reaction [48] ... 

Table 7. Summary of Inorganic Reductions by Sodium Borohydride ...

J. Seyden-Penne, Reductions by the Alumino- and Borohydrides in Organic Synthesis, 2nd Edn, J. Wiley Sons, New York, 1997. ISBN 1560819391. 

It is quickly deacylated in vivo and may qualify as a prodrug. The published synthesis is rather long and bears conceptual similarities to the synthesis of cannabinoids. It has some five asymmetric centers. Dane salt formation between 3,5-di-methoxyani1ine and ethyl acetoacetate followed by borohydride reduction gives synthon The amino group is protected by... 

Fenticonazole (106), on the other hand, is used topically to combat a wide variety of dermatophytes and yeasts, particularly Candida albicans. It can be synthesized from 2,4-dichlo-rophenacyl chloride (104) by reduction with borohydride and subsequent displacement with imidazole to give 105. This last undergoes ether formation with p-thiolphenylbenzyl chloride mediated by NaH to produce fcnticonazole (106) [37]. 

The formation and structures of unstable products from nuclear reduction of 2,3-dimethoxyquinoxaline by borohydride or electrochemical means have been studied. ... 

Norbomenone 26 undergoes reduction by sodium borohydride under kinetic conditions to produce 5% exo- (i.e., endo attack) and 95% endo- (i.e., exo attack) 2-norbomeol. This leads to the partial rate constants of 11.4 for exo and 0.6 for endo attack (relative rate with respect to the rate of LiAlH reduction of cyclopen-tanone (1.00)) [80]. In the saturated 2-norbomanone 25, the values are 4.55 for exo and 0.74 for endo attack. Thus, the introduction of the double bond enhances the... 

There are reports (reviewed in Ref. (55)) of acetylene reduction by FeMoco using very powerful reductants such as sodium borohydride or sodium amalgam. Unfortunately, in most of these experiments the integrity of FeMoco after reaction was not established, and thus the reaction could have been carried out by fragments of FeMoco. Reduction of acetylene bound to a metal site by powerful reductants is well established. 

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