合成路线:This compound can be obtained by two related ways:1) The reaction of L-lysine (I) with NaNO2 - H2SO4 in water gives 6-amino-2(S)-hydroxyhexanoic acid (II),which is protected with benzyl chloroformate as usual yielding the N-benzyloxycarbonyl compound (III).The condensation of (III) with L-proline benzyl ester (IV) by means of hydroxybenzotriazole (HBT) and dicyclohexylcarbodiimide (DCC) affords the acylated proline ester (V),which is esterified with 4-phenylbutylphosphonous acid (VI) by means of DCC and dimethylaminopyridine (DMAP),and oxidized with NaIO4 to give the protected phosphonic ester (VIII).Finally,this compound is debenzylated by hydrogenation of Pd/C in methanol.The phosphonous acid (VI) is obtained by reaction of 4-phenyl-1-butene (VII) with sodium hypophosphite by means of azobisisobutyronitrile (AIBN).2) The condensation of acylated proline ester (V) with dibenzyl 4-phenylbutylphosphonate (IX) by means of PCl5,triethylamine and DMAP also gives the protected phosphonic ester (VIII).The dibenzyl phosphonate (IX) is obtained by condensation of 4-phenylbutyl chloride (X) with dibenzyl phosphite (XI) by means of NaH in DMF.
参考文献标题:SQ-29852
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(6),533
合成路线:This compound can be obtained by two related ways:1) The reaction of L-lysine (I) with NaNO2 - H2SO4 in water gives 6-amino-2(S)-hydroxyhexanoic acid (II),which is protected with benzyl chloroformate as usual yielding the N-benzyloxycarbonyl compound (III).The condensation of (III) with L-proline benzyl ester (IV) by means of hydroxybenzotriazole (HBT) and dicyclohexylcarbodiimide (DCC) affords the acylated proline ester (V),which is esterified with 4-phenylbutylphosphonous acid (VI) by means of DCC and dimethylaminopyridine (DMAP),and oxidized with NaIO4 to give the protected phosphonic ester (VIII).Finally,this compound is debenzylated by hydrogenation of Pd/C in methanol.The phosphonous acid (VI) is obtained by reaction of 4-phenyl-1-butene (VII) with sodium hypophosphite by means of azobisisobutyronitrile (AIBN).2) The condensation of acylated proline ester (V) with dibenzyl 4-phenylbutylphosphonate (IX) by means of PCl5,triethylamine and DMAP also gives the protected phosphonic ester (VIII).The dibenzyl phosphonate (IX) is obtained by condensation of 4-phenylbutyl chloride (X) with dibenzyl phosphite (XI) by means of NaH in DMF.
参考文献标题:(Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme (ACE).1.Discovery of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline,a novel orally acting inhibitor of ACE
文献作者:Powell,J.R.; Karanewsky,D.S.; Dejneka,T.; DeForrest,J.M.; Petrillo,E.W.Jr.; Perri,M.G.; Badia,M.C.; Loots,M.J.; Cushman,D.W.
参考来源:J Med Chem 1988,31(1),204
产品链接: CAS No. 111223-26-8››