Sodium cyanoborohydride, reductive amination with

Figure 7.11 Oxidation of glycoproteins with periodate, such as glycosylated antibodies, results in the formation of aldehyde groups that can be used for conjugation to dendrimers containing amine groups. Reductive amination with sodium cyanoborohydride results in coupling via secondary (or tertiary) amine bonds.

REDUCTIVE AMINATION WITH SODIUM CYANOBOROHYDRIDE N,N-DIMETHYLCYCLOHEXYL-... 

FNA was synthesized by reaction of /(-naltrexamine (48) with the monomethyl ester of fumaroyl chloride [79], Amine (48) was prepared first from naltrexone by reductive amination with sodium cyanoborohydride in the presence of ammonium acetate to give 6a- and 6/i-epimers (ratio ca. 2 1). Separation was achieved by fractional crystallization [83], An improved synthesis of (48) was reported via the dibenzyliminium salt of naltrexone (46 easily accessible from naltrexone and dibenzylamine) which was reduced with sodium cyanoborohydride to give exclusively the 6/i-epi-mer (47). Catalytic hydrogenolysis afforded /i-naltrexamine (Scheme 3.6) [84]. 

REDUCTIVE AMINATION WITH SODIUM CYANOBOROHYDRIDE N.N-DIMETHYLCY-CLOHEXYLAMINE, 52, 124 Reference electrode for electrolytic reduction, 52, 28 Resorcinol dimethyl ether, 50,52 Rhodium-on-alumina, catalyzed reduction of aromatic nuclei, 51, 105... 

You met reductive amination with sodium cyanoborohydride in Chapter 11, p. 234. 

The influence of glycosylation on tissue uptake of enzymes has been investigated. Lactose and A-acetylneuraminyl-Iactose have been coupled to Escherichia coli L-asparaginase by reductive amination with sodium cyanoborohydride (see Scheme 2, Vol. 10, Part II, Chapter 8, p. 428). Oligosaccharides obtained from... 

Oligosaccharides derived from baker s yeast D-mannan have been coupled to human serum albumin by reductive amination with sodium cyanoborohydride. [ " C]-Labelled derivatives containing two or four D-mannose residues per 10000 mol. wt. were administered intravenously to rats selective uptake of these derivatives by the endothelial and Kupffer cells of the liver was observed within ten to fifteen minutes. The extent of hepatic uptake was a function of the number and size of the D-manno-oligosaccharides coupled. Reductive manno-samination may provide a means of directing proteins of potential therapeutic interest towards specific liver cells. 

A combined reductive amination sequence has been developed as a useful way of synthesizing amines, with sodium cyanoborohydride as the reducing agent of choice. This complex metal hydride is a less reactive version of sodium... 

Rather than preforming the a-amino ketimines to be reduced, it is often advantageous to form in situ the more reactive iminium ions from a-aminoketones and primary amines or ammonium salts in the presence of the reducing agent, e.g., sodium cyanoborohydride. Use of this procedure (reductive amination) with the enantiopure a-aminoketone 214 and benzylamine allowed the preparation of the syn diamines 215 with high yields and (almost) complete diastereoselectivities [100] (Scheme 32). Then, the primary diamines 216 were obtained by routine N-debenzylation. Similarly, the diamine 217 was prepared using ammonium acetate. In... 

Scheme 32 Reductive amination of chiral a-aminoketones with sodium cyanoborohydride...

Schiff base interactions between aldehydes and amines typically are not stable enough to form irreversible linkages. These bonds may be reduced with sodium cyanoborohydride or a number of other suitable reductants (Chapter 2, Section 5) to form permanent secondary amine bonds. However, proteins crosslinked by glutaraldehyde without reduction nevertheless show stabilities unexplainable by simple Schiff base formation. The stability of such unreduced glutaraldehyde conjugates has been postulated to be due to the vinyl addition mechanism, which doesn t depend on the creation of Schiff bases. 

Figure 3.14 Carbonyl groups can react with amine nucleophiles to form reversible Schiff base intermediates. In the presence of a suitable reductant, such as sodium cyanoborohydride, the Schiff base is stabilized to a secondary amine bond.

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... 

Figure 14.21 Aldehyde-particles can be reacted with amine-containing proteins or other molecules to form intermediate Schiff bases, which can be stabilized by reduction with sodium cyanoborohydride.

Hapten molecules containing aldehyde residues may be crosslinked to carrier molecules by use of reductive animation (Chapter 3, Section 4). At alkaline pH values, the aldehyde groups form intermediate Schiff bases with available amine groups on the carrier. Reduction of the resultant Schiff bases with sodium cyanoborohydride or sodium borohydride creates a stable conjugate held together by secondary amine bonds. 

Thus, glycoproteins such as HRP, GO, or most antibody molecules can be activated for conjugation by brief treatment with periodate. Crosslinking with an amine-containing protein takes place under alkaline pH conditions through the formation of Schiff base intermediates. These relatively labile intermediates can be stabilized by reduction to a secondary amine linkage with sodium cyanoborohydride (Figure 20.8). 

REDUCTION OF ALKYL HALIDES AND TOSYLATES WITH SODIUM CYANOBOROHYDRIDE IN HEXAMETHYL-PHOSPHORAMIDE (HMPA) A. 1-IODODECANE TO n—DECANE B. 1-DODECYL TOSYLATE TO n-DODECANE, 53, 107 REDUCTION OF KETONES BY USE OF TOSYLHYDRAZONE DERIVATIVES ANDROSTAN-17 0—OL, 52, 122 REDUCTIVE AMINATION WITH SO-... 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

Vinylamines (enamines) are reduced by alane, mono- and dichloroalane to saturated amines, and hydrogenolyzed to amines and alkenes [710]. Reduction is favored by dichloroalane while hydrogenolysis is favored by alane. Alane, chloroalane and dichloroalane gave the following results with -N-pyrrolidinylcyclohexene V-pyrrolidinylcyclohexane in 13, 15 and 22% yield, and pyrrolidine and cyclohexene in 80, 75 and 75% yields, respectively [710]. Saturated amines were also obtained by treatment of enamines with sodium borohydride [711], with sodium cyanoborohydride [103, 712] (Procedure 22, p. 210) and by heating for 1-2 hours at 50-70° with 87% or 9S% formic acid (yields 37-89%) [320]. 

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

The overall carbon-nitrogen framework was confirmed by synthesis. Reductive amination of the triketone (336) (429) with sodium cyanoborohydride and ammonium acetate formed a mixture of four isomeric pyrrolizidines. Pure sam-... 

Dialkylpyrrolidines. These compounds can be prepared by reductive amination of 1,4-diketones with sodium cyanoborohydride and ammonium acetate (4, 448-449). 1-Pyrrolines are usually formed also, but they can be reduced to pyrrolidines by NaBH4 in a second step.1... 

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