New bestatin derivs. are cpds. of formula R1CH(NH2).CH(OH).CO.NH.CH(R2).COOH (I), where R1 is hydroxybenzyl; and R2 is 1-6C alkyl, hydroxyalkyl, mercaptoalkyl, carboxamidoalkyl, alkoxyalkyl, alkylmercaptoalkyl, carboxyalkyl, aryl, aralkyl or substd. aralkyl. Specific cpds. (I) include (2RS, 3RS)-3-amino-2-hydroxy-4-(p-hydroxyphenyl)-butyryl-(5)-leucine. In an example, this is prepd. by (a) refluxing Z-(2RS, 3RS)-3-amino-2-hydroxy-4-(p-methoxyphenyl)butyronitrile with conc. HCl and dioxan in the presence of anisole; (b) reacting the resulting (2RS, 3RS)-3-amino-2-hydroxy-4-(p-hydroxyphenyl)butyric acid with Z-Cl in the presence of NaOH; (c) reacting the resulting Z-(2RS, 3RS)-3-amino-2-hydroxy-4-(p-OZ-phenyl)butyric acid with Leu-OB3I in the presence of N-hydroxybenzotriazole; and (d) hydrogenating the resulting Z-(2RS, 3RS)-3-amino-2-hydroxy-4-(p-OZ-phenyl)-butyryl-(5)-leucine benzyl ester over palladium black.
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机译:新的Bestatin衍生。是cpds。式R1CH(NH2).CH(OH).CO.NH.CH(R2).COOH(I)的化合物,其中R1是羟基苄基; R 2是1-6C烷基,羟基烷基,巯基烷基,羧酰胺基烷基,烷氧基烷基,烷基巯基烷基,羧基烷基,芳基,芳烷基或亚甲基。芳烷基。特定的cpds。 (I)包括(2RS,3RS)-3-氨基-2-羟基-4-(对羟基苯基)-丁酰基-(5)-亮氨酸。在一个示例中,这是准备的。通过(a)将Z-(2RS,3RS)-3-氨基-2-羟基-4-(对甲氧基苯基)丁腈与浓溶液回流。苯甲醚存在下的HCl和二恶烷; (b)在NaOH存在下使所得的(2RS,3RS)-3-氨基-2-羟基-4-(对羟基苯基)丁酸与Z-Cl反应; (c)在N-羟基苯并三唑存在下,使所得的Z-(2RS,3RS)-3-氨基-2-羟基-4-(对-OZ-苯基)丁酸与Leu-OB3I反应; (d)在钯黑上氢化所得的Z-(2RS,3RS)-3-氨基-2-羟基-4-(对-OZ-苯基)-丁酰基-(5)-亮氨酸苄酯。
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