(±)-沙美特罗昔萘酸盐的全合成

Total Synthesis of (±)-Salmeterol Xinafoate

以对羟基苯乙酮为原料,经氯甲基化、酯化、溴代、水解和二醇保护等反应制得1-(2,2-二甲基-4H-1,3-苯并二氧芑-6-基)-2-溴乙酮(6);首次以(±)-α-苯乙胺为胺化试剂,6经胺化反应得1-(2,2-二甲基-4H-1,3-苯并二氧芑-6-基)-2-(1-苯乙氨基)乙酮(7);7经NaBH4还原得1-(2,2-二甲基-4H-1,3-苯并二氧芑-6-基)-2-[α-苯乙氨基]乙醇(8);8经脱苄、亲核取代、脱保护及成盐等反应合成了(±)-沙美特罗昔萘酸盐,总收率5.8%。其中7和8为新化合物,其结构经1H NMR,IR和MS表征。

1 - （2,2-Dimethyl） -4H-1, 3-benzodioxin-6-yl） -2-bromoethanone （6） was prepared by chlo- romethylation, esterification, bromination, hydrolysis and dihydroxy protection using 4-hydroxyaceto- phenone as the starting material. 1 - （ 2,2 -Dimethyl） -4H-1,3 -benzodioxin-6 -yl ） -2 - （ 1 -phenylethylami- no） ethanone（7） was prepared by amination of 6 using （ ± ）-1-phenylglycinol as the amination reagent for the first time. 1 - （ 2,2 -Dimethyl） -4H-1,3 -benzodioxin-6 -yl ） -2 - （ 1 -phenylethylamino ） ethanol （8） was obtained by reduction of 7 with NaBH4. （ ± ）-Salmeterol xinafoate was synthesized by debenzylation of 8, and then nucleophilic substitution, deprotection and formating salt. The total yield was 5.8 %, 7 and 8 were new compounds. The structures were characterized by 1H NMR, IR and MS.