The Aldol reaction catalyzed by DNA proline in water.doc

Early studies revealed that L-proline could catalyze the direct aldol reaction, but in many case obtaining racemic product in aqueous medium. Moreover, considering that Golefes group reported the DNA based asymmetric catalysis, DNA could interact with amino acids through H bond, which was constituent part of protein or recognized as the smallest protein in asymmetric catalysis. We assume that the enantioselectivity could be improved if this type of chiral acid served as an additive in the L-proline catalyzed aldol reactions, due to a cooperative effect in the catalytic system (Scheme 1). In this paper, we report an improved L-proline catalyzed aldol reaction in aqueous medium. Under the optimized conditions, the aldol product was afforded in up to 53% in aqueous medium.Scheme 1Table 1 The Aldol reaction catalyzed by DNA-proline in water EntryDNA-proline(mmol)bYield %Ee%10.0389.7Rac.20.03212730.06263340.12243250.243828Reaction conditions: DNA: 10mg, 4-nitrobenzaldehyde: 0.1mmol, H2O:1.5ml, acetone: 1.5ml, rt for 5d. a: no DNA. b: mole of the proline. Table 2 The effect of water in the ee for the DNA-proline catalyzed aldol reaction of acetone with 4-nitrobenzaldehyde EntryH2O%Yield %Ee%Ee%a10767065225605393402342Rac.4502633Rac.5662834Rac.6751611Rac.Reaction conditions: DNA: 10mg, L-proline: 0.06mmol, 4-nitrobenzaldehyde: 0.1mmol, rt for 5d. a: no DNAThe effect of water-acetone ratio on the enantiomeric excess of the product was also investigated (Table 2). The lower ee so much as racemic product was obtained in the presence of water catalyzed by L-proline only, however, in the presence of DNA, it was obtained enantioselective product. The ee was from 53% to 11%, accompanying with the ratio of water from 25% to 75% (entry 2-6). In organic medium, the presence of DNA could also increase the ee from 65% to 70%. It was demonstrated that DNA played an important role in the aldol reaction in aqueous medium. Table 3 The effect of the concentration of the substrate and the catalystEntrySubstrate(mmol)Yield %Ee %10.0313.820.1234230.2284140.331425a0.14141Reaction conditions: DNA: 10mg, , H2O:1.0ml, acetone: 1.5ml, rt for 5d. a: DNA:20mg. L-proline : 0.12mmolTable 4 The source of the chiralityEntryCatal. systemYield %Ee %1Proline + A93Rac.2Proline + T91Rac.3Proline + G88Rac.4Proline + C89Rac.Reaction conditions: base: 0.03mmol, L-proline: 0.06mmol, 4-nitrobenzaldehyde: 0.1mmol, H2O:1.5ml, acetone: 1.5ml, rt for 2d. Table 5 The source of the chiralityEntryCatal. systemYield %Ee %1L-Proline + dAMP13312L-Proline + dTMP15263L-Proline + dGMP15304L-Proline + dCMP13285L-proline + DNA2342Reaction conditions: nucleotide: 0.03mmol, L-proline: 0.06mmol, 4-nitrobenzaldehyde: 0.1mmol, H2O:1.0ml, acetone: 1.5ml, rt for 5d. Table 6 The effect of other amino acidsEntryDNA + AAYield %Ee %1L-Phe33182L-Leu33213L-Ala17194L-CysNR-5L-Trp26116L-Glu20227L-Arg8388L-His73Rac.9L-Lys874Reaction conditions: DNA: 10mg, amino acid: 0.06mmol, 4-nitrobenzaldehyde: 0.1mmol, H2O:1.0ml, acetone: 1.5ml, rt for 5dThe catalytic ability of other amino acid was also investigated (Table 6). The acidic and neutral amino acid gave better result than that of basic amino acid (entry 1-3, 6 vs 7-9), which gave better reaction rate. Because of interaction of DNA with amino acid through H-bond tightly, the acti