Oxidation catalytic antibodies

Naturally occurring redox enzymes have been successfully exploited for asymmetric synthesis for some years.1 Although impressive chemo-, regio-, and enantioselectivities have been achieved in some cases, these biocatalysts have prescribed selectivity and often require expensive cofactors that must be recycled for preparative work. Catalytic antibodies offer an attractive alternative, since they are not limited a priori by Nature s choices. Thus the need for cofactor recycling can be circumvented through the use of inexpensive oxidants and reductants, and, as we have seen above, selectivity can be tailored through appropriate hapten design. 

A retro hetero Diels-Alder reaction to release an anthracene derivative 9-9 and nitroxyl (HNO) from the corresponding cycloadduct 9-8 by a catalytic antibody has been described by Reymond and Lerner [565]. As a haptene the acridinium salt 9-10 was used (Fig. 9-3). The antibody obtained is of great biological interest as a prodrug release system since the liberated nitroxyl is easily oxidized by the ubiquitous enzyme superoxide dismutase to give nitric oxide (NO) which acts as a chemical messenger for several important bioregulatory processes. 

Epoxide hydrolysis is a valuable synthetic transformation. A number of epoxide hydrolase enzymes are known [37]. One of the most interesting and original transformations described using catalytic antibodies is the intramolecular cyclization of racemic hydroxyepoxide 17 (Scheme 7). This compound normally yields tetrahydrofuran 19a following Baldwin s rule. By contrast a single enantiomer of the disfavored product tetrahydropyran 20 a is obtained using a catalytic antibody raised against A-oxide hapten 16 [38]. The same antibody also catalyzes cyclization of hydroxyepoxide 18 to yield optically enriched oxepane... 

Diels-Alder reaction releasing, besides nitroxyl which can be converted to nitric oxide, a strongly blue fluorescent anthracene product 64 (Scheme 22) [99]. This reaction can therefore be followed sensitively in cell culture supernatants. Using early screening we have isolated seven different catalytic antibodies for the reaction out of approximately 12,000 individual cell culture wells resulting from fusions with ten different immunized mice. Due to early screening, the experiment was completed in a matter of weeks and comprised cloning of only a handful of antibodies [100]. 

In the line of catalytic antibodies development, Nimri and Keinan reported that the incorporation of the Ru(II) porphyrin (12 in Figure 10.11) within a specially raised monoclonal antibody (mAb) catalyzed the enantioselective oxidation of aromatic sulfides. Great care was taken in the design of the hapten from which the mAb was elicited so that it mimicked the transition state. For stability reasons, the hapten was an Sn(IV) porphyrin and one of the axial positions was occupied by an a-naphthoxy ligand. In the presence of excess mAb, the Ru porphyrin catalyzed the sulfoxidation of thioanisole and analogs (see Scheme 10.9) with up to 43% ee (S) [57]. 

---