Diels-Alder cycloaddition, catalytic antibodies

Earlier this year the same group described the preparation of novel imprinted polymers with Diels-Alder cycloaddition capabilities [52], The imprinting system was inspired by the same approach used by Gouvemeur et al. for the preparation of catalytic antibodies for Diels-Alder cycloaddition [53]. The reaction between 1,3-butadiene carbamic acid benzylester (78) and A,lV -dimethylacrylamide (79) to give the corresponding endo- and exo-products (80) was chosen as a target. The imprinted polymer made it possible to enhance 20-fold the rate of the reaction when compared with the background. 

Scheme 3. The highly-ordered transition state associated with the Diels-Alder reaction has made it a natural target for work in the field of catalytic antibodies [15]. Indeed, Hilvert [15a] has reported recently the first successfully antibody-catalyzed Diels-Alder reaction. Monoclonal antibodies elicited to the boxed hapten 14 provided both acceleration of and multiple turnover of the cycloaddition between tetrachlorothiopene dioxide and IV-ethyl maleimide. The initial adduct decomposes by the chelotropic-extrusion of sulfur dioxide affording the dihydrophthalimide derivative 13...

Keywords Catalytic antibody. Hapten, Enantiofacial, Enantioselective, Diels-Alder cycloaddition, Cationic reactions, Aldol condensation. Disfavored cyclization... 

The transition state of Diels-Alder reaction of diene 56 with dienophile 57 to give the adduct 58 (Scheme 5.14) is a boat-like type. The antibody 39-Al 1, generated to the bicy-clo [2.2.2 ] octane hapten 59 that mimics the transition state of the reaction, efficaciously catalyzed the cycloaddition, selectively giving 58 in buffered aqueous medium (Scheme 5.14). ° Ribozymes are RNA molecules with catalytic properties. Artificial ribozymes, isolated fi om synthetic combinatorial libraries, accelerate a broad range of reactions including the Diels-Alder cycloaddition. These ribozymes generally require that at least one of the reactants be RNA or be covalently tethered to RNA. 

Catalytic antibody 1E9, the first catalytic antibody discovered for Diels-Alder reaction, catalyzes the cycloaddition between tetrachlorothiophene dioxide and N-ethylmaleimide (Equation 4.15) [86]. 

The question whether Diels-Alder reactions also occur in nature can not be answered yet since special enzymes catalyzing these reactions have not been found so far [24-25]. However, artificial catalytic antibodies for Diels-Alder reactions are well known [26] and recently an all-carbon [4 + 2]cycloaddition has been observed in the biosynthesis of two phytotoxic solanopyrones 1-1 and 1-2 from the fungus Alternaria solani using a cell-free extract of this organism [27] it is highly probable that the involved enzymes will soon be isolated (Fig. 1-2). 

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