依维莫司的合成

Synthesis of Everolimus

雷帕霉素与2-[(四氢-2H-吡喃-2-基)氧基]乙基三氟甲磺酸酯在有机碱作用下缩合得到40-O-[(四氢-2H-吡喃-2-氧基)乙基]雷帕霉素,然后直接在酸性条件下脱除缩醛保护基,最后经制备液相分离纯化得到依维莫司,总收率约66%。该路线选择性较好,反应条件温和,具有工业应用价值。

Everolimus was synthesized from rapamycin via condensation with 2-[ （tetrahydro-2H-pyran- 2-yl） oxy] ethyl trifluoromethanesulfonate in the presence of organic base to give 40-0- [ [ （tetrahydro-2H-pyran-2- yl） oxy] ethyl] rapamycin, which was subjected to deprotection under acidic conditions directly. The crude product was isolated and purified by prep-HPLC, and the overall yield was about 66 %. This route had better selectivity, mild reaction condition, and industrial application.