Study Of Preparative Production Of (s)-2-Methyl-1-Butanol Via Porcine Pancreatic Lipase Catalysis

Lipase has great potential as catalysts for use in organic synthesis, because of their high catalytic efficiency and stereoselectivity. As research of lipase catalyzed reaction in non-aqueous phase proceeds, more study and application are reported. Because of the importance of chiral drugs, considerable efforts have been made in developing biotransformation for the production of chiral drugs.With the theory of lipases' catalyzed transesterification in non-aqueous organic media, racemic 2-methyl-1-butanol was resoluted by porcine pancreatic lipase (PPL) with tributyrin, vinyl acetate and triacetin respectively served as substrate and organic phase. Thus, an optical active alcohol, (s)-2-methyl-1-butanol was obtained.In the preparative research of the alcohol with tributyrin served as substrate and organic phase, A TLC method for quickly and convenientively monitoring resolution reaction was developed, which is suitable in range from 30% to 55% reaction proceeding and with ±3% deviation compared with HPLC; Purity of product was increased by combining distillation with column chromatography in separation process; The alcohol with high purity and productivity is obtained at 55% reaction proceeding; Higher temperature and more water not only denature PPL, but also decrease stereoselectivity of PPL.In a new system with vinyl acetate served as substrate and organic phase, the resolution proceeded smoothly after acetaldehyde was removed by 4A sieve. Suitable operation conditions for the new system in existence of free PPL were achieved. The conditions include T 25℃,pH=7.5, substration proportion dl-2-methyl-1-butanol: vinyl acetate=1:1.6(mol/mol), stirring rate 260rmp. (s)-2-methyl-1-butanol with 72.3% optical purity was obtained under the conditions above. As for catalyzing ability, immobilized PPL surpasses free PPL. Polar supports surpass hydrophobic ones in the diversity of supports. It shows that celite is greater than any other support .As to another new system with triacetin served as substrate and organic phase, available conditions are as follow: T 40℃,pH=7.5, substration proportion dl-2-methyl-1-butanol: triacetin =1:1.3(mol/mol), stirring rate 260rmp. (s)-2-methyl-1-butanol with 62.6% optical purity was obtained under the conditions. As for catalyzing ability, immobilized PPL is prior to free PPL. Polar supports surpass hydrophobic supports in the diversity of supports. It shows that celite is greater than any other support..Optical purity of products become lower after replacing substrate with new ones, but the results have their value from economical and industrial viewpoint. And it can provide some experimental basis and experience for further research.