A-Hydroxyl-co-carboxyl asymmetric

The convenient synthesis of a-hydroxyl-co-methoxycarbonyl asymmetric telechelic PIBs has been achieved by the combination of two recently discovered techniques, haloboration-initiation and end capping with 1,1-diphenylethylene followed by end quenching with silyl ketene acetals, 1 -methoxy-1 -trimethylsiloxy-2-methyl-propene (MTSMP), 1-methoxy-1-trimethylsiloxy-propene (MTSP), and 1-methoxy-l-trimethylsiloxy-ethene (MTSE). Nearly quantitative chain end functionalization has been proved by NMR, quantitative NMR, and FT-IR spectroscopy. The methoxycarhonyl end arising by quenching with MTSMP could not be hydrolyzed under either basic or acidic conditions. These methods also failed to yield the acid when the corresponding diisobutylene derivative was used. The sterically less hindered esters, however, readily underwent hydrolysis resulting in the formation of a-hydroxyl-co-carboxyl asymmetric telechelic PIBs. 

Combination of the head and end group control provides a novel synthetic route for the synthesis of a-hydroxyl-co-methoxycarbonyl asymmetric telechelic PIB H0PIBC(R)(R )C00CH3 (a condensation macromonomer). Hydrolysis of the methoxycarbonyl end group results in the formation of a-hydroxyl-co-carboxyl asymmetric telechelic PIB HOPIBC(R)(R )COOH, while ester dcoholysis provides a method for polycondensation reactions of PIB. In the present publication we report the synthesis of these materials. 

Some biotransformations introduce an asymmetric center into a drug and these often proceed stereospeci-fically. The most common examples are hydroxylation of a secondary carbon and the reduction of ketones to secondary alcohols. Ibuprofen undergoes both co and co-l oxidation of the isobutyl side chain, and formation of the resulting carboxylic acid metabolite introduces a second asymmetric center into the molecule. Both ibuprofen enantiomers have been shown to undergo stereospecific oxidation to give a metabolite with the same configuration at the new asymmetric center. 

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