Study On Syntheses Of Chiral Hydantoin& Cyclic Dipeptide And Their Effects On Asymmetric Cyanohydrination

Asymmetric synthesis of optically active cyanohydrins is very important to thedevelopment of medical and agrochemical products, while chiral hydantoins andchiral cyclic dipeptides are the effective asymmetric catalysts for synthesis of them.For example, (S)-α-cyano-3-phenoxybenzylalcohol is an important precursor forsynthesis of a series of optically active pyrethroids such as deltamethrin andfenvalerate. Asymmetric synthesis of chiral cyanohydrins is the key step to producechiral pyrethroids with high optical activity. First of all, the enantioselectivity of theprepared chiral hydantoins and chiral cyclic dipeptides was mainly studied byapplication them to asymmetric cyanohydrination of 3-phenoxy benzaldehyde.Second, in connection with industrialization process, the asymmetric catalytic efficacyof these catalysts was also observed in the synthesis of fenvalerate by reaction ofbutylric acid chloride and 3-phenoxyphenylaldehyde, which have practical andtheoretical value.The methods of preparation of 3,5-disubstituted chiral hydantoins from aminoacids were been studied. A series of chiral hydantoin compounds[ (5S or5R)-5-(5-substituted) -3-phenyl-2,4- imidazolidinedione, 1a,1b,1c,1d,1e,1f,1g,1h,1iand 1j], were obtained by condensation and cyclization of amino acids with phenylisocyanates or benzyl isocyanates. These ten kinds of hydantoin all have opticalactivity and have been identified by elementary analysis, IR, HNMR and 1 13 CNMR.Some improvements were made in condensation reactions, such as mixed solventswere used instead of water alone and an effective method of separating condensationproduct and by-product (diarylurea), which ensured hydantoins with high purity.And effects of the ratio of raw materials, pH value of solution, reaction temperatureand reaction time et al on preparation of chiral hydantoins, have been discussed indetail. These studies led to the conclusion that, optimally, the reaction should be run atthe pH of condensation 1.5-2.0 high than the isoelectrics point of amino acid, molarratio of isocyanates to amino acids is about 1.2-1.4, the cyclization reaction time isbetween 3.5-4h. The result of the experiment indicated that, the improved process ofchiral hydantoin preparation has many advantages, such as rapid reaction, betterproduct and higher yield of 75%. The products 1c and 1d had not been reportedbefore.The process of preparation of cyclic dipeptides from L-phenylalanine (D-phenylalanine , L-leucine) and L-histidine ( as the raw materials) was studied. The i韩邦友:手性海因,环二肽的合成及不对称氰醇化研究 2004 年 5 月peptide was linked after protection of amino group in phenylalanine (leucine) andcarboxyl group in histidine, then the protective group was removed by hydrogenation,cyclization was completed under refluxing in methanol. As a result, a series of chiralcyclic dipeptides were obtained. The prepared cyclic dipeptides and their precursorswhich all have certain optical activity have been identified to be the expectedstructures by m.p., elementary analysis, IR, HNMR and CNMR. The two methods 1 13of preparation of chiral cyclodipeptides, such as "mixed anhydrides" and "activeesters" were been studied. And effects of the molar ratio of raw materials,concentration of reactants, reaction temperature, reaction time et al., have beenstudied in detail. Especially, the crystal form of cyclic dipeptides and absorption byactive carbon were studied, so that the purity and asymmetric catalytic effectivenessof target product was good. With study of many experiments and in order to takeadvantage of phosgene in Jiangsu Kuaida Agrochemical Co., Ltd. improvement wasmade in active esterification in which liquid alkaline was replaced by solid alkalineand phosphorus oxychloride was replaced by phosgene. The result of the experimentshowed that with higher yield of 65%, less pollution, easily obtained raw materials,low cost, the simplified process was easier to industrialize than...