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Glutamine dipeptide synthesis process of non-steroidal anti-inflammatory analgesics - Zaltoprofen synthesis research

Author: JinHui
Tutor: ZhongYuGuo;TangWeiGao
School: Sichuan University
Course: Medicinal Chemistry
Keywords: Glutamine Glutamine dipeptide Glycyl -L-glutamine L - alanyl -L glutamine Synthesis
CLC: TQ463
Type: Master's thesis
Year: 2003
Downloads: 398
Quote: 1
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Abstract


L-glutamine (Gln) is a conditional essential amino acid, but low solubility in water, the solution instability and other shortcomings, which limit their widespread clinical use. (Glycyl-L-glutamine, glycyl-L-glutamine, GQ) and L-alanyl-L glutamine (AQ) is found in recent years, L-glutamine, a water-soluble prodrug, they have good water solubility and stability properties of in vivo easy to explain the release of the enzyme L-glutamine characteristics, better clinical evaluation. In this paper, on the basis of relevant literature reference, with the active ester method Available Gan glycyl-L-glutamine and L-alanine glycyl-L-glutamine dipeptide, and conducted a detailed study of its process, found one suitable for industrial-scale production line. Glycine and L-alanine as a starting material, the first of its amino group with benzyloxycarbonyl protection, the active ester of the corresponding hydroxy succinimide (HOSu), and then condensed with L-glutamine, The hydrogen release de-protecting group was willing to glycyl-L-glutamine and L-alanyl the acyloxy-L-glutamine dipeptide, the total yield of the four-step reaction were 30%, 25%. This process raw materials readily available, each step mild reaction conditions, the operation is relatively simple, low-cost. Chloride method synthesis Gan aminoacyl-L-glutamine was. Further study of the related substances in the dipeptide of L-glutamine, synthetic 6 related substances. FAB target structure and related substances by IHNMR, '3 CNMR, IRMS EI, MS and elemental analysis. Active cool Preparation of L a glutamyl Thalidomide the skin 0 HOOC HR IC HN O == C 0} CH20CCI (Z a CI) R, two rushing DCC public NHZCHC00HH Dan O O C-HR IC NH a O two CO 2 HC bee one O one hundred eleven ---- the \O00 the raw type once the bucket H, NCCH, CH, at first glance HC oHNHC CHZNH} 11 0RR = H GQR = CH3 AQ0u phthalocyanine chloride prepared glycyl phthalocyanine L valley ammonia phthalocyanine amine 0 \CH, Han Hc oH NHZ Me0H' ----- Diao Bu H2504Ro a CcH, CH, at first glance Hc oH NHZCICHZC an OH-a ---- Diao Bu PH = 0 \write Hco gung NH row H, c, O NH3 to under edge known H Qing CCH, cH, yeah HC-oH 10 O Two O N ICCH little old 2 \

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