Reductive-Amination-Mediated Conjugation

The use of periodate coupling chemistry for HRP first was introduced by Nakane and Kawaoi (1974 see also Nakane, 1975). In the first step of their protocol, the few amine groups on HRP were initially blocked with 2,4-dinitrofluorobenzene (DNFB) before periodate oxidation. 

Reductive animation coupling forming secondary amine linkage 

---

Reductive Amination-Mediated Hapten-Carrier Conjugation... 

In some cases, the ability to modify glycans at the reducing end without reduction preserves the carbohydrate s native structure sufficiently to allow interactions with proteins that would otherwise not interact if the bond were reduced. Therefore, depending on the ultimate use of the biotinylated carbohydrate, using a hydrazide mediated conjugation process can have advantages over the use of amine-biotin compounds. 

In the same year, Zhou and List reported a novel one-pot tandem reaction which, for the first time, combined chiral Bronsted acid catalysis with enamine and iminium catalysis. Later, on the basis of control experiments and ESI-MS/MS analysis, a reasonable mechanism was proposed (Scheme 2.2). The initial step of this tandem reaction was mediated by achiral /j-ethoxyaniline (PEP-NH2) and chiral phosphoric acid (R)-TRIP either reagent alone was inefficient in promoting this aldol condensation to afford the first iminium intermediate. The following step was a conjugate reduction which was also Bronsted acid and amine co-catalysed, and no further conversion took place in the absence of either catalyst. The final step was an acid-catalysed reductive amination. This novel sequence allowed the highly enantioselective synthesis of pharmaceutically active chiral ds-3-substituted cyclohejyl or heterocyclohexyl amines in high diastereo- and... 

A short synthesis of (-f)-monomorine (1562) by Maruoka and coworkers used the chiral phase-transfer catalyst (R)-1672 to mediate an enantioselective conjugate addition between enone 1673 and the imine-protected glycine ester 1674 (Scheme 213). In a remarkable one-pot reaction, the intermediate adduct 1675 was then treated with Hantzsch ester (diethyl 2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylate) in mildly acidic medium, which brought about deprotection of the acetal and imine as well as a double reductive amination in which the dihydropyridine acted as the hydrogen transfer agent. The resulting indolizidine ester (—)-1676 was... 

---