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Stereoselective Aldol Additions Catalyzed by Dihydroxyacetone Phosphate-Dependent Aldolases in Emulsion Systems: Preparation and Structural Characterization of Linear and Cyclic Iminopolyols from Aminoaldehydes

Authors

  • Laia Espelt Dr.,

    1. Department of Peptide and Protein Chemistry Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain, Fax: (+34)93-4006112
    2. Department of Surfactant Technology Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain
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  • Teodor Parella Dr.,

    1. Servei de Ressonància magnètica Nuclear, Universitat Autònoma de Barcelona, Bellaterra, Spain
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  • Jordi Bujons Dr.,

    1. Department of Biological Organic Chemistry (DBOC) Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain
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  • Conxita Solans Dr.,

    1. Department of Surfactant Technology Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain
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  • Jesús Joglar Dr.,

    1. Research Unit on Bioorganic Molecules (RUBAM) Department of Biological Organic Chemistry Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain
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  • Antonio Delgado Dr.,

    1. Research Unit on Bioorganic Molecules (RUBAM) Department of Biological Organic Chemistry Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain
    2. Unitat de Química Farmacèutica, Facultat de Farmacia, Universitat de Barcelona, Spain
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  • Pere Clapés Dr.

    1. Department of Peptide and Protein Chemistry Institute for Chemical and Environmental Research-CSIC, Jordi Girona 18 – 26, 08034 Barcelona, Spain, Fax: (+34)93-4006112
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Abstract

The potential of dihydroxyacetone phosphate (DHAP)-dependent aldolases to catalyze stereoselective aldol additions is, in many instances, limited by the solubility of the acceptor aldehyde in aqueous/co-solvent mixtures. Herein, we demonstrate the efficiency of emulsion systems as reaction media for the class I fructose-1,6-bisphosphate aldolase (RAMA) and class II recombinant rhamnulose-1-phosphate aldolase from E. coli (RhuA)-catalyzed aldol addition between DHAP and N-benzyloxycarbonyl (N-Cbz) aminoaldehydes. The use of emulsions improved the RAMA-catalyzed aldol conversions by three to tenfold relative to those in conventional DMF/water mixtures. RhuA was more reactive than RAMA towards the N-Cbz aminoaldehydes regardless of the reaction medium. With (S)- or (R)-Cbz-alaninal, RAMA exhibited preference for the R enantiomer, while RhuA had no enantiomeric discrimination. The linear N-Cbz aminopolyols thus obtained were submitted to catalytic intramolecular reductive amination to afford the corresponding iminocyclitols. This reaction was diastereoselective in all cases examined; the face selectivity was controlled by the stereochemistry of the newly formed hydroxyl group originating from the aldehyde. Characterization of the resulting iminocyclitols allowed the assessment of the diastereoselectivity of the enzymatic aldol reactions with respect to the N-protected aminoaldehyde. RAMA formed single diastereoisomers from N-Cbz-glycinal and from both enantiomers of N-Cbz-alaninal, while 14 % of the epimeric product was observed from N-Cbz-3-aminopropanal. Diastereoselectivity from RhuA was lower than that observed from RAMA. Interestingly, a single diastereoisomer was formed from (S)-Cbz-alaninal, whereas only a 34 % diastereomeric excess was observed from its enantiomer (i.e., (R)-Cbz-alaninal).

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