Synthesis Of The New Anti-HIV/HBV Agent ET And Anti-cancer Agent CAP

The first part of this dissertation is the study on synthesis of ET (emtricitabine ; FTC).It was a kind of nucleoside reverse transcriptase inhibitor drug,which was developed jointly by American Emory university and triangle pharmic company and marketed in july,2003.It is a kind of nucleoside antivirus drug developed in the base of lamivudine. ET ,combined with other drugs,can be used to cure AIDS or HBV. It has strong antivirus effect as well as security and good enduration.ET was synthesized through two processes. The first process is synthesis through six steps with dithiane-l,4-diol and glyoxylic acid with 50% water solution as starting materials, and at the same time the process was optimized as follows:(l) glyoxylic acid monohydrate replace with cheap glyoxylic acid with 50% water solution;(2) the yield of L-menthol was increased to 35% from 22%;(3) In the forth step when oxathiolane and silylated 5-Fu was coupling, two methods were used: first, the expensive imported reagent TMSOTf was replaced by lewis acid SnCl₄;second, initially transfer OAc to Cl, then coupling silylated 5-Fu . (4)The reduction was conducted NaBH₄ instead of LiAlH₄, at the same time we found a method of a recrystallization, avoiding silica gel column chromatography mentioned in the literature. The process above has good stability, reiteration and lower cost and easily to industrialisation. The second process is synthesized through eight steps with S- (-) -mandelic acid as starting material. In this process 2-position chirality was obtained by S- (-) -mandelic acid, then selective reduction lactone by DIBAL—H or LTTBA, after coupling silylated-Fu, 5-position chirality was obtained by diastereomeric recrystallization and target molecule was got through the alkali hydrolysis in methanol solution of ammonia.The second part of this dissertation is the study on synthesis CAP. It is a kind of new-style 5-fluorouracil , 5-FU developed's pre-medicament by Switzerland Rhodes company, authorized into clinic treatment by FDA in Sep, 1998. And it was authorized again curing ambulant rectum cancer. CAPis the first examined and approved new-style oral fluorin emiction pyridine' s pre-medicament.It is tumour cell selective fluorin emiction pyridine' s pre-medicament, which can make tumour cell keep upper 5— FU level and has lower virulence and wide range of effective dosage.In this dissertation, CAP is obtained with D-ribose as starting material through a 7-steps process by hydroxy protection, reduction, silylation coupling, acetylation, deprotection under alkali hydrolysis . The last two steps , excellent reagent condition are found to avoid column chromatography.