Sodium cyanoborohydride, reaction with

Sodium cyanoborohydride. reductive ami nation with, 931 Sodium cyclamate, LP50 of, 26 Sodium hydride, reaction with alcohols, 605... 

The reactivity of these tricyclic compounds has been investigated in detail. Reaction of these with sodium cyanoborohydride in acetic acid reduces the imine double bonds to give the tetrahydro-derivatives, for example, 37 gives 39. Reaction of 37 with sodium methoxide results in the ring-opened sulfonate salt 40 re-acidification of this salt gives the corresponding sulfonic acid which cyclizes back to the tricycle 37. Further heating of the sulfonic acid... 

An interesting procedure has been proposed for the synthesis of amylose-b-PS block copolymers through the combination of anionic and enzymatic polymerization [131]. PS end-functionalized with primary amine or dimethylsilyl, -SiMe2H groups were prepared by anionic polymerization techniques, as shown in Scheme 56. The PS chains represented by the curved lines in Scheme 56 were further functionalized with maltoheptaose oligomer either through reductive amination (Scheme 57) or hydrosilyla-tion reactions (Scheme 58). In the first case sodium cyanoborohydride was used to couple the saccharide moiety with the PS primary amine group. 

Aldehyde-containing macromolecules will react spontaneously with hydrazide compounds to form hydrazone linkages. The hydrazone bond is a form of Schiff base that is more stable than the Schiff base formed from the interaction of an aldehyde and an amine. The hydrazone, however, may be reduced and further stabilized by the same reductants utilized for reductive amination purposes (Chapter 3, Section 4.8). The addition of sodium cyanoborohydride to a hydrazide-aldehyde reaction drives the equilibrium toward formation of a stable covalent complex. Mallia (1992) found that adipic acid dihydrazide derivatization of periodate-oxidized dextran (containing multiple formyl functionalities) proceeds with much greater yield when sodium cyanoborohydride is present. 

Figure 1.114 The reaction of a reducing sugar with an amine-containing compound in the presence of sodium cyanoborohydride results in ring opening with the formation of a secondary amine derivative.

Derivatives of hydrazine, especially the hydrazide compounds formed from carboxylate groups, can react specifically with aldehyde or ketone functional groups in target molecules. Reaction with either group creates a hydrazone linkage (Reaction 44)—a type of Schiff base. This bond is relatively stable if it is formed with a ketone, but somewhat labile if the reaction is with an aldehyde group. However, the reaction rate of hydrazine derivatives with aldehydes typically is faster than the rate with ketones. Hydrazone formation with aldehydes, however, results in much more stable bonds than the easily reversible Schiff base interaction of an amine with an aldehyde. To further stabilize the bond between a hydrazide and an aldehyde, the hydrazone may be reacted with sodium cyanoborohydride to reduce the double bond and form a secure covalent linkage. 

Glutaraldehyde is the most popular b/s-aldchydc homobifunctional crosslinker in use today. Flowever, a glance at glutaraldehyde s structure is not indicative of the complexity of its possible reaction mechanisms. Reactions with proteins and other amine-containing molecules would be expected to proceed through the formation of Schiff bases. Subsequent reduction with sodium cyanoborohydride or another suitable reductant would yield stable secondary amine... 

In a fume hood, add 10 pi of 5M sodium cyanoborohydride (Sigma) per ml of reaction solution. Caution cyanoborohydride is extremely toxic. All operations should be done with care in a fume hood. Also, avoid any contact with the reagent, as the 5M stock solution is dissolved in 1 N NaOH. If a higher pH buffer was used for the Schiff base formation, then adjust the solution to pH 7.5 before adding the cyanoborohydride. 

Aldehyde particles are spontaneously reactive with hydrazine or hydrazide derivatives, forming hydrazone linkages upon Schiff base formation. Reactions with amine-containing molecules, such as proteins, can be done through a reductive amination process using sodium cyanoborohydride (Figure 14.21). 

Proteins may be modified with oxidized dextran polymers under mild conditions using sodium cyanoborohydride as the reducing agent. The reaction proceeds primarily through e-amino groups of lysine located at the surface of the protein molecules. The optimal pH for the reductive amination reaction is an alkaline environment between pH 7 and 10. The rate of reaction is greatest at pH 8-9 (Kobayashi and Ichishima, 1991), reflecting the efficiency of Schiff base formation at this pH. 

Santagada and coworkers have disclosed a reductive amination method for the generation of a reduced peptide bond by reaction of a protected amino acid aldehyde with an N-deprotected amino ester using sodium cyanoborohydride as reducing agent [296]. 

Takano s group reported the first enantioselective total synthesis of (—)-anti-rhine as well (146). Chiral product 235 was prepared via a number of stereoselective reactions. Reductive condensation of 235 with tryptamine, using sodium cyanoborohydride at pH 6, supplied lactam 236, which was reduced by di-isobutylalminum hydride to hemiacetal 237. The latter could be cyclized to (-)-antirhine by simple acid treatment (146). 

A major achievement in augmenting the chemical potential of antibodies has been in the area of redox processes. Many examples now exist of stereoselective reductions, particularly recruiting sodium cyanoborohydride (Appendix Section 22). A growing number of oxidation reactions can now be catalysed by abzymes, with augmentation from oxidants such as hydrogen peroxide and sodium periodate (Appendix Section 21). 

The reductive amination of hexane-2,5-dione and heptane-2,6-dione with ammonia and primary amines RNH2 (R = PhCH2, Ph2CH, PhMeCH, Ph, 4-MeOC6H4, 2-ClC6H4 and 2,6-Me2CgH3) under the influence of sodium cyanoborohydride or sodium triacetoxyboro-hydride has been studied. The reactions yield respectively pyrrolidines and piperidines as mixtures of cis- and fraws-isomers no cyclic products were obtained when 2-chloroaniline of 2,6-dimethylaniline were employed (equation 57)168. 

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