佛波酯磷脂酰-L-丝氨酸(PEPS)中间体的合成工艺改进

Improved synthesis of two intermediates of phorbol ester-phosphatidyl-L-serine

目的改进佛波酯磷脂酰-L-丝氨酸(PEPS)的中间体3-苄基-2-(8-叔丁基二苯基硅氧辛酰基)-1-三苯甲基-sn-甘油(9)和N-叔丁氧羰基-L-丝氨酸二苯甲酯(11)的合成工艺。方法以D-甘露醇为原料,经丙叉基保护、氧化-还原、苄基保护、脱丙叉保护、选择性保护、酯化、羧基还原、硅烷基保护合成化合物9;以L-丝氨酸为原料,经氨基、羧基保护合成化合物11。结果与结论目标化合物的结构经1H-NMR谱确证,改进后的工艺,缩短了合成路线,简化了柱色谱分离、纯化步骤,具有原料易得,操作简便,成本低廉的优点。

Aim To improve the synthetic procedure of 3- benzyl-2- （ 8- tert-butyldiphenylsilyloxyoctanoyl）- 1- triphenylmethyl-sn-glycerol（9） and N-Boc-L-serine diphenylmethyl ester（11）. Methods The compound 9 was synthesized from D-mannitol via eight steps reaction including isopropylidene acetal formation, oxidation-reduction, benzylation, deprotection, selective tritylation of the primary alcohol, esterification, reduction of the carboxylic acid, silylation. The compound 11 was synthesized from L-serine via Boc-protection of amino group and diphenylmethyl ester formation. Results and conclusion The structure of the target compounds were confirmed by ^1H-NMR. A more convenient and efficient procedure was obtained by reducing synthetic steps and using easily available material.