Study On Cyclodipeptides Catalysis Synthesis Of Optically Active Cyanohydrination

Optically active cyanohydrin is one of the very important intermediates in agrochemical and pharmacy industry. Being one of the main intermediates for synthesis of optically active pyrethroides, (S)-aIpha-cyano-3-phenoxybenzyl alcohol is getting more and more attention. Chiral cyclic dipeptide is an effective catalyst for asymmetric cyanohydrin synthesis. Researchers had studied the catalysis effect of different dipeptides and found that the best result was obtained with cyclo(Phe-His).The "natural" peptide cyclo(L-Leu-L-His) gives the opposite streoselectivity to cyclo(L-Phe-L-His), which provides (S)-cyanohydrins and this dipeptide can be preparaed easily and cheaply. Based on the studies of predecessors, we have studied mainly the asymmetric synthesis of cyclo(Phe-His), cyclo(L-Leu-L-His) and it's catalysis process and the results have certain theory and application value.Obtained dipeptides cyclo(L-Phe-L-His), cyclo(L-Leu-L-His), cyclo(D-Phe-D-His) by condensation of N-terminal protected L-phenylalanine,L-Leucine, D- phenylalanine and C-terminal protected L-histidine, Pd/C catalytic hydrogenating and cyclizing. Elemental analyses, IR and 'HNMR elucidated their structures. The products were further treated by fractional crystallized from different solvents or by filtered through silica and so on. Different processes have given the product different form that varied from white crystal to gray gel.Conditions of dipeptide catalysis asymmetric addition of hydrogen cyanide to aldehyde to produce (S)-alpha-cyano-S-phenoxybenzyl alcohol and then (S, S)-fenvalerate have been studied and improved. With HCN as the source of CN, ether/ toluene as solvent,the value of pH is great than 7.0, reaction time is 15 hours and the reaction temperature is at 0~-10, aldehyde has been coverted to cyanohydrin and then (S, S)-fenvalerate catalysis by cyclo(L-Leu-L-His) in 85% yield and 37% enantiomeric excess (e.e.). Also, with HCN as the source of CN", toluene as solvent, reaction time is 4 hours and the reaction temperature is at 0癈, aldehyde has beencoverted to cyanohydrin and then (S, S)-fenvalerate catalysis by cyclo(D-Phe-D-His) in 41% yield and 72% enantiomeric excess. The catalytic property can be affected greatly by the solvent. Among various solvents examined, toluene seems to be the best solvent. In addition to the importance of the solvent effect, the aggregation state of the dipeptides also affects the catalytic property. Those dipeptides precipitated from low-pole or non-pole solvents with a form to be a kind of amorphism performed better than those perfectly purified.