合成路线:Antineopleston A10 (A10) can be obtained by two different ways:1) A10 has been synthesized in two steps: Condensation of phenylacetic acid (I) with L-glutamine (V) to give phenylacetyl-L-glutamine (VI),followed by intramolecular cyclization of the latter.In the first step (I) is activated by reacting with various reagents such as HOSu (N-hydroxysuccinimide) (II) in the presence of DCC,DCC (N,N-dicyclohexylcarbodiimide) or 2-mercaptothiazoline (III) in the presence of DCC to afford the intermediates (IVa),(IVb) and (IVc),respectively.Without isolation,the intermediate (IVa),(IVb) or (IVc) is treated with a solution of L-glutamine in CH3CN:H2O (2:1) containing NaHCO3 to give (VI) in 60,87 and 82% yields,respectively.In the second step (VI) is converted to the activated intermediate (IXa) or (IXb) by treatment with CDI (1,1'-carbonydiimidazole) (VII) or HOSu (VIII) in the presence of DCC.Finally,intramolecular cyclization of (IXa) or (IXb) is effected by treating the latter at 80 C to yield A10 in 85 or 82% yield,respectively.2) Reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords phenylacetyl-L-glutamine (VI),which is heated at 160 C to give A10.
参考文献标题:Antineoplaston A10
文献作者:Burzynski,S.R.; Hai,T.T.
参考来源:Drugs Fut 1985,10(2),103
合成路线:Antineopleston A10 (A10) can be obtained by two different ways:1) A10 has been synthesized in two steps: Condensation of phenylacetic acid (I) with L-glutamine (V) to give phenylacetyl-L-glutamine (VI),followed by intramolecular cyclization of the latter.In the first step (I) is activated by reacting with various reagents such as HOSu (N-hydroxysuccinimide) (II) in the presence of DCC,DCC (N,N-dicyclohexylcarbodiimide) or 2-mercaptothiazoline (III) in the presence of DCC to afford the intermediates (IVa),(IVb) and (IVc),respectively.Without isolation,the intermediate (IVa),(IVb) or (IVc) is treated with a solution of L-glutamine in CH3CN:H2O (2:1) containing NaHCO3 to give (VI) in 60,87 and 82% yields,respectively.In the second step (VI) is converted to the activated intermediate (IXa) or (IXb) by treatment with CDI (1,1'-carbonydiimidazole) (VII) or HOSu (VIII) in the presence of DCC.Finally,intramolecular cyclization of (IXa) or (IXb) is effected by treating the latter at 80 C to yield A10 in 85 or 82% yield,respectively.2) Reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords phenylacetyl-L-glutamine (VI),which is heated at 160 C to give A10.
参考文献标题:
文献作者:Verhoef,J.; Schmitz,F.-J.; Fluit,A.C.; Milatovic,D.
参考来源:13th Intl Cong Chemother (Aug.28-Sept.2,Vienna) 1983,50(2),PS 12.4-11-4
产品链接: CAS No. 91531-30-5››