Spisulosine 285, Spisulosine, ES-285
Chemical Name: 2(S)-Aminooctadecan-3(R)-ol
CAS No. 196497-48-0
项目整合开发状态: Phase I
项目研究机构: PharmaMar (Originator), University of Illinois (Originator)
合成路线:Alanine methyl ester (I) was protected by N-alkylation with benzyl bromide to afford (II),which was further reduced to amino alcohol (III) using LiAlH4.Swern oxidation of (III) provided aldehyde (IV).Addition of the Grignard reagent obtained from 1-bromopentadecane (A) to aldehyde (IV) produced the anti-aminoalcohol (V).The N-benzyl groups were finally removed by catalytic hydrogenolysis.
合成路线:In a different procedure,dibenzyl malonate (VI) was alkylated with tetradecyl bromide (B) to afford (VII).This was then condensed with N-phthaloyl-L-alanyl chloride (VIII) in the presence of NaH,and the resulting keto diester (IX) was subjected to hydrogenolysis of the benzyl esters and further thermal decarboxylation to furnish ketone (X).Ketone reduction with simultaneous partial reduction of the phthaloyl group yielded (XI) and (XII) as a diastereomeric mixture.After chromatographic separation,the desired isomers were deprotected by reductive cleavage with NaBH4 to provide the corresponding amino alcohol.
📌 参考资料/链接：
参考文献标题:Spisulosine cpds.having antitumour activity
文献作者:Garcia Gravalos,D.; Warwick,R.A.; Avila,J.; Rinehart,K.L.; Fregeau,N.L.; Faircloth,G.T.(University of Illinois)
参考来源:WO 9952521
📄 详细内容
合成路线:Alanine methyl ester (I) was protected by N-alkylation with benzyl bromide to afford (II),which was further reduced to amino alcohol (III) using LiAlH4.Swern oxidation of (III) provided aldehyde (IV).Addition of the Grignard reagent obtained from 1-bromopentadecane (A) to aldehyde (IV) produced the anti-aminoalcohol (V).The N-benzyl groups were finally removed by catalytic hydrogenolysis.
合成路线:In a different procedure,dibenzyl malonate (VI) was alkylated with tetradecyl bromide (B) to afford (VII).This was then condensed with N-phthaloyl-L-alanyl chloride (VIII) in the presence of NaH,and the resulting keto diester (IX) was subjected to hydrogenolysis of the benzyl esters and further thermal decarboxylation to furnish ketone (X).Ketone reduction with simultaneous partial reduction of the phthaloyl group yielded (XI) and (XII) as a diastereomeric mixture.After chromatographic separation,the desired isomers were deprotected by reductive cleavage with NaBH4 to provide the corresponding amino alcohol.
参考文献标题:The marine compound spisulosine,an inhibitor of cell proliferation,promotes the disassembly of actin stress fibers
文献作者:Cuadros,R.; Montejo de Garcini,E.; Wandosell,F.; Faircloth,G.; Fernandez-Sousa,J.M.; Avila,J.
参考来源:Cancer Lett 2000,152(1),23
产品链接: CAS No. 196497-48-0››