文献类型：专利

英文题名：Synthesis of pyrrolysine includes reacting 2,2-dimethyl propionaldehyde and glycine methyl ester hydrochloride to form methyl-(E)-2-(2,2-dimethyl propyleneamino)acetate, and performing Michael addition reaction and hydrolyzing

作者：DUAN M;GAO J;LI X;LUO X;SUN L;YUE W;ZHOU Y

机构：[1]UNIV EAST CHINA SCI & TECHNOLOGY

申请号：CN101709047-A

申请日：2009-05-25

公开日：2010-05-19

语种：英文

收录：DERWENT

摘要：NOVELTY - A pyrrolysine is synthesized by reacting 2,2-dimethyl propionaldehyde and glycine methyl ester hydrochloride to form methyl-(E)-2-(2,2-dimethyl propyleneamino)acetate, performing Michael addition reaction and hydrolyzing to obtain pyrrole ring, sulfidizing and methylating pyrrole ring to condense with lysine, and desulfidizing and demethylating. USE - Method of synthesizing pyrrolysine (claimed). ADVANTAGE - The method has low cost, uses easily obtained raw materials, has moderate and easily controlled reaction conditions, and uses simple reaction devices. The obtained intermediate compounds in the reaction are stable. Each reaction in the synthesis is quantitative and has high yield. DETAILED DESCRIPTION - A pyrrolysine is synthesized by: (A) refluxing glycine methyl ester hydrochloride, benzene, 2,2-dimethyl propionaldehyde and triethyl amine at 80-120 degrees C for 1-3 hours to obtain (E)-2-(2,2-dimethyl propyleneamino)acetate; (B) mixing obtained compound with tetrahydrofuran, lithium bromide, ethyl crotonate and 1,8-diazabicyclo(5.4.0)undec-7-ene, to generate Michael addition reaction at 10-50 degrees C for 10-30 minutes to obtain methylethyl-2-(2,2-dimethyl propyleneamino)-3-methyl glutarate; (C) mixing obtained addition product with methanol, water and acetic acid, performing acidolysis at 60-100 degrees C, and cyclizing to obtain 3-methyl-2-hydroxymethyl ester-5-oxopyrrolidine; (D) mixing obtained oxopyrrolidine compound with tetrahydrofuran and Ravaisson reagent, reacting at 10-50 degrees C for 1-3 hours to obtain 3-methyl-2-carboxymethyl ester-5-thiopyrrolidine; (E) reacting thiopyrrolidine compound with acetone and methyl iodide, performing methylation reaction at 0-40 degrees C for 10-18 hours to give 3-methyl-2-carboxymethyl ester-5-thiomethyl-3,4-dihydro-2H-pyrrole; (F) mixing the pyrrole compound with tetrahydrofuran, water and sodium hydroxide, hydrolyzing, condensing with methyl-(R)-6-amino-2-trifluoroacetylaminoacetate under the catalysis of diphenylphosphoryl azide at 10-50 degrees C for 3-6 hours to obtain methyl-(2R)-6-(3-methyl-5-thiomethyl-3,4-dihydro-2H-pyrrole-2-amido)-2-trifluoroacetylamino-caproate; (G) reacting caproate compound with tetrahydrofuran, water and methanol in lithium hydroxide at 10-50 degrees C for 4-10 hours to obtain lithium-(2R)-2-amino-6-(3-methyl-5-thiomethyl-3,4-dihydro-2H-pyrrole-2-amido)caproate; and (H) reacting obtained compound with acetone and Raney nickel, and heating at 40-80 degrees C for 0.5-3 hours to obtain pyrrolysine lithium salt.