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佛波酯磷脂酰-L-丝氨酸(PEPS)中间体的合成工艺改进
  • 期刊名称:中国药物化学杂志,2008,18,268-272.
  • 时间:0
  • 分类:R914[医药卫生—药物化学;医药卫生—药学]
  • 作者机构:[1]北京大学药学院天然药物及仿生药物国家重点实验室,北京100083
  • 相关基金:国家自然科学基金项目(20172005)
  • 相关项目:以RNA为靶的氨基糖苷类抗生素的化学改造
中文摘要:

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。H-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。

英文摘要:

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.

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