Racemic haptens

Racemic haptens have the advantage of synthetic expedience, but they do not always yield (R)- and (S)-specific catalysts in a single experiment. The eighteen catalytic antibodies obtained with the tripeptide phosphonate 6,14 for example, only catalyzed the hydrolysis of substrates (7) containing D-phenylalanine at the cleavage site. Depsipeptides containing leucine or tryptophan in place of phenylalanine were not hydrolyzed. The selectivity for d- over... 

Selenoxide syn-eliminations are another reaction type favoured by less polar solvents (Reich, 1979). The planar 5-membered, pericyclic transition state for syn-elimination of [39] was mimicked by the racemic proline-based cis-hapten [39] to give 28 monoclonal antibodies (Appendix entry 8.5) (Zhou et al., 1997). Abzyme SZ-cts-42F7 converted substrate [40] exclusively into... 

Fig. 25) (Baldwin, 1976). By raising antibodies to the charged hapten [67], Janda and co-workers produced an abzyme which accelerated 6-exo attack of the racemic epoxide to yield exclusively the disfavoured tetrahydropyran product [68] and in an enantiomerically pure form (Appendix entry 14.1) (Janda et al 1993). 

Figure 18 Kinetic resoiution of racemic naproxen ester 28 by antibody 15G2 raised against hapten 27.

Mu YQ, Gibbs RA. Design and synthesis of chiral and racemic phosphonate-based haptens for the induction of aldolase catalytic antibodies. Biooig. Med. Chem. 1997 5(7) 1327—1337. 

Selected Biological Aspects. - The design and preparation of haptens (390) and (391) for catalytic antibody-promoted dynamic kinetic resolution of racemic 4-substituted 4H-oxazolin-5-ones have been reported. Transition state mimicry and a bait and switch strategies were adopted to propose the structure of the haptens. A key step in their synthesis is based on a ring-closing metathesis reaction. ... 

Conjugation of a racemic drug to a protein increases the possibility for heterogeneous antisera because at least two haptens (R and S) are introduced. The immune system could respond by producing antibodies to only one enantiomer, or varying amounts of antibodies to each enantiomer. Each antibody may also have affinity for the opposite enantiomer. The use of racemic radioligands further complicates the situation. These problems have been discussed by Maeda and Tsuji (23), Cook et al. (24), and Rominger and Albert (25). 

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... 

The immunoaffinity chromatography of auxins is carried out in the same way. Effective immunosorbents have been described for antibodies prepared to each of the three types of lAA-hapten-protein conjugates [135-137]. For abscisic add, immunoaffinity chromatography has not only been used to isolate the hormone from plant extracts [138], but also has found use in the enantiomeric separation of commercially available racemic [ H]-abscisic acid [139-140]. 

Fig. 3 (A) [33] Sigrnatropic rearrangement of chorismate to prephenate catalyzed by antibody 11F1-2E11. The hapten is a shape mimic of the cyclic transition state. (B) Antibody 1E9 catalyzes a Diels-Alder reaction of tetrachlorothiophene dioxide and yV-ethylmaleimide. The hapten is comprised of the endo hexachloronorbornene unit. (C) Antibody 21H3A catalyzes the transesterification reaction between iec-phenethyl alcohol and an enolic ester to form a chiral ester. The hapten here is racemic phosphonate.

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