Ecraprost, AS-013

依克前列素Chemical Name: 9-O-Butyryl-8,9-didehydroprostaglandin F1 butyl ester; 9-(Butyryloxy)-11alpha,15(S)-dihydroxyprosta-8,13(E)-dien-1-oic acid butyl ester; 2-(Butyryloxy)-4(R)-hydroxy-5(R)-[3(S)-hydroxy-1(E)-octenyl]-1-cyclopentene-1-heptanoic acid butyl ester
CAS No. 136892-64-3
项目整合开发状态: Phase III
项目研究机构: Asahi Glass (Originator), Seikagaku (Originator), Mitsubishi Pharma (Codevelopment)
合成路线:Treatment of (1E,3S)-1-iodo-3-(tert-butyldimethylsilyloxy)-1-octene (I) with BuLi in ethyl ether,followed by reaction with 7-[3(R)-(tert-butyldimethylsilyloxy)-5-oxo-1-cyclopenten-1-yl] heptanoic acid butyl ester (II) by means of tributylphosphine-copper(I) iodide complex and tributylphosphine in ethyl ether provides the protected nonisolated intermediate (III),which is treated with butyric anhydride (IV) to afford derivative (V).Finally,this compound is converted into the desired product by removal of the TBDMS groups by means HF in acetonitrile/H2O (1).Alternatively,the synthesis can be performed by following a different protection strategy: Esterification of carboxylic acid (VI) with butyl iodide in DMSO by means of diisopropylamine provides derivative (VII),which is then protected by reaction with 3,4-dihydro-2H-pyran (VIII) to furnish compound (IX).Next,coupling of (IX) with iodo derivative (I) by means of tert-BuLi,tributylphosphine - copper (I) iodide complex and tributylphosphine in ethyl ether gives the adduct (X),which by reaction with butyric anhydride (IV) affords derivative (XI).Finally,this compound is converted into the desired product by following this deprotection protocol: 1) Bu4NF in THF; 2) Ac2O,DMAP in CH2Cl2 in the presence of pyridine; and finally 3) pyridinium p-toluenesulfonate (PPTS) in EtOH.