摘要
基于手性膦配体(2S,4S)-2-二苯膦甲基-4-二苯膦基四氢吡咯(PPM)合成了一种新型的氨基酸型两性水溶性手性膦配体的前体。首先以(2S,4S)-N-Boc-2-对甲苯磺酰氧甲基-4-对甲苯磺酰氧基四氢吡咯(1)为起始原料与二苯基膦化钠反应,再经膦硫化得到(2S,4S)-N-Boc-2-二苯硫膦甲基-4-二苯硫膦基四氢吡咯(2),收率67.2%;化合物2用过量的三氟乙酸处理脱去Boc保护基得到(2S,4S)-2-二苯硫膦甲基-4-二苯硫膦基四氢吡咯(3),收率94.0%;化合物3与N-Boc-L-天冬氨酸-4-苄酯缩合得到(2S,4S)-N-[(2′S)-2′-叔丁氧酰胺基-3′-苄氧酰基丙酰基]-2-二苯硫膦甲基-4-二苯硫膦基四氢吡咯(4),收率95.8%;化合物4再用三溴化硼脱去保护基得到目标产物(2S,4S)-N-[(2′S)-2′-氨基-3′-羧基丙酰基]-2-二苯硫膦甲基-4-二苯硫膦基四氢吡咯(5),收率54.2%。
The zwittefionic water-soluble chiral diphospbines ligands with amino acid moieties are synthesized based on chiral diphosphines ligand PPM. The reaction of (2 S, 4 S ) -N- Boc-4- ( p-toluenesulfonyloxy )-2- [ ( p-toluenesulfonyloxy ) methyl] pyrrolidine(1) with sodium diphenylphosphine and further treatments with sulfide can give in 67.2% yield the (2S,4S)-N- Boc-4-(diphenylphosphinothioyl)-2-[ (diphenylphosphinothioyl) methyl] pyrrolidine (2),which is then converted by treatments with a excess of trifluoroacetic acid to ( 2S, 4S )-4-( diphenylphosphinothioyl)-2-[ ( diphenylphosphinothioyl ) methyl ] pyrrolidine (3) in 94.0% yield. Subsequent reaction of 3 with Boc-Asp(OBzl)-OH affords the (2S,4S)-N-[(2'S)-3'- benzyloxycarbonyloxy-2' - ( tert- butoxycarbonamido) propionyl ]-4- ( diphenylphosphinothioyl )-2-[ ( diphenylphosphinot hioyl) methyl ] pyrrolidine (4) in 95.8% yield. The removal of protecting groups of 4 with boron tribromide give (2S,4S)-N- I[ (2'S)-2'-amino- 3'-carboxy]propionylt -4-(diphenylphesphinothioyl)-2-[(diphenylphosphinothioyl) methyl] pyrrolidine in 54.2% yield.
出处
《现代化工》
CAS
CSCD
北大核心
2010年第1期68-70,共3页
Modern Chemical Industry
基金
国家自然科学基金(20606019)资助项目
关键词
手性膦配体
氨基酸
两性
合成
chiral phosphines ligands
amino acid
zwitterionic
synthesis