Group 13-Based Reducing Agents

Certain base adducts of borane, such as triethylamine borane [1722-26-5] (C2H )2N BH, dimethyl sulfide borane [13292-87-OJ, (CH2)2S BH, and tetrahydrofuran borane [14044-65-6] C HgO BH, are more easily and safely handled than B2H and are commercially available. These compounds find wide use as reducing agents and in hydroboration reactions (57). A wide variety of borane reducing agents and hydroborating agents is available from Aldrich Chemical Co., Milwaukee, Wisconsin. Base displacement reactions can be used to convert one adduct to another. The relative stabiUties of BH adducts as a function of Group 15 and 16 donor atoms are P > N and S > O. This order has sparked controversy because the trend opposes the normal order estabUshed by BF. In the case of anionic nucleophiles, base displacement leads to ionic hydroborate adducts (eqs. 20,21). 

Fructose bisphosphate aldolase of animal muscle is a Class I aldolase, which forms a Schiff base or imme intermediate between the substrate (fructose-1,6-bisP or dihydroxyacetone-P) and a lysine amino group at the enzyme active site. The chemical evidence for this intermediate comes from studies with the aldolase and the reducing agent sodium borohydride, NaBH4. Incubation of fructose bisphosphate aldolase with dihydroxyacetone-P and NaBH4 inactivates the enzyme. Interestingly, no inactivation is observed if NaBH4 is added to the enzyme in the absence of substrate. 

The requirement for reduction prior to DNA alkylation and crosslinking was first demonstrated by Iyer and Szybalski in 1964 [29], and can be induced both by chemical reducing agents such as sodium dithionite and thiols in vitro and by various reductive enzymes such as DT-diaphorase (NAD(P)H-quinone oxidoreduc-tase) in vitro and in vivo [47]. Much work to characterize the mechanism of reductive activation and alkylation has been carried out, principally by the Tomasz and Kohn groups, and Figure 11.1 illustrates a generally accepted pathway for mitomycin C [16, 48-50] based on these experiments, which is very similar to the mechanism originally proposed by Iyer and Szybalski [29]. 

Substitution at the SiH moiety has been carried out with alkylthio groups, such as MeS and i-PrS. Tn s(alkylthio)silanes, (RSlsSiH, are radical-based reducing agents which can effect the reduction of bromides, iodides, xanthates, phenylselenides, and isocyanides in toluene, using AIBN as the initiator at 85... 

Figure 4.21 BASED can react with molecules after photoactivation to form crosslinks with nucleophilic groups, primarily amines. Exposure of its phenyl azide groups to UV light causes nitrene formation and ring expansion to the dehydroazepine intermediate. This group is highly reactive with amines. The cross-bridge of BASED is cleavable using a disulfide reducing agent.

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. 

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