Synthesis Of Non-steroidal Anti-inflammatory Drugs The Darboux Dragon And Alkaloid Halofuginone

This paper is made up of the synthesis of the non-steroidal anti-inflammatory drugs(NSAIDs) darbufelone and alkaloid halofuginone.The first part is on the synthesis of darbufelone, whose chemical name is (Z)-5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]-2-imino-4-thiazolidinone, methanesulfonate salt. It is the product of the Warner-Lambert company for treatment of osteoarthritis(OA) and rheumatoid arthritis(RA). The synthesis method ,in which the key intermediate, (Z)-5-[[3,5-bis(1,1-dimethylethyl )-4-hydroxyphenyl]methylene]-2-imino-4-thiazolidinone (CI-1004) , is prepared from 3,5-di-tert-butyl-4-hydroxybenzaldehyde and pseudothiohydantoin, has a low yield and is protected by patent. So we designed a simple and new one, which employed 3,5-di-tert-butyl-4-hydroxybenzaldehyde, chloroacetyl chloride and thiourea as raw materials and afforded a higher yield. Besides, we got the key intermediate CI-987 of Tazofelone which is a new inflammatory bowel disease agent through similar process. The structures of the products were characterized by ¹HNMR, ¹³CNMR, DEPT,H-HCOSY,HSQC,HMBC,IR and MS.The other part is on the synthesis of alkaloid halofuginone. Halofuginone, whose chemical name is 3-[3-[3 (S)-HydroxyPiperidin-2 (R)-yl] -2- oxopropyl ] -7-bromo-6-chloro-3,4-dihydroquinazolin-4-one, and febrifugine, whose chemical name is 3-[3-[3 (S)- Hydroxypiperidin-2 (R) -yl]-2-oxopropyl]-3,4-dihydro quinazolin-4-one, and isofebrifugine,. whose chemical name is 3-[(3aS,7aS)-2-Hydroxyperhydrofuro [3,2-b] pyridin-2- yunethyl]-3,4-dihydroquinazolin-4-one, were discovered as alkaloids with excellent biological activity in last century. Halofuginone has been used as an antiparasitic feed additive for the prevention of coccidiosis in poultry production and is now undergoing clinical trials for treatment of scleroderma in human. Febrifugine and isofebrifugine exhibit potent anti-malarial activity and, to date, no parasite resistance to has been reported.