Penicillanic Acids

摘要

1,179,060. Penicillins; N-carboxy amino acid anhydrides. AMERICAN HOME PRODUCTS CORP. 10 July, 1968 [28 July, 1967], No. 32834/68. Headings C2A and C2C. The invention relates to penicillins of Formula I or a salt thereof, wherein R1 and R2 are the same or different and each is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryl or aryloxy and n is 1 or 2. Typical salts are the Na, K, hydrochloride, sulphate or fumarate. A typical penicillin is 6-(indan-2- amino-2-carboxamido) penicillanic acid. The penicillins are produced by reacting:-(A) 6- aminopenicillanic acid or a salt thereof with a N-carboxy amino acid anhydride of Formula VI wherein R1, R2 and n have the above values. (B) 6-APA with an acid of Formula V (where R1, R2 and n have the above meaning) in which the amino group is protected, or a salt thereof, and thereafter removing the protecting group under sufficiently mild conditions to avoid destruction of the penicillin nucleus. (C) a silyl drivative of 6-APA of formula (where R4 is H or and R5, K6 and R7 are the same or different and each is an alkyl, cycloalkyl, aryl or aralkyl group) or a solution comprising such a silyl derivative, with an acid of Formula V, or a reactive derivative thereof, and wherein the amino group is protected by reacting the acid in the form of its N-carboxy anhydride, and thereafter removing the silyl groups by hydrolysis or alcoholysis. The N-carboxyamino acid anhydrides of Formula VI are prepared by the following reaction scheme :- wherein R1, R2 and n have the above meaning and Z is -CH < or -CH 2 -CH <. Examples are for the preparation of the N-carboxy anhydrides of 2-amino indane-2-carboxylic acid and its 4-phenyl, 3-phenoxy and 4-butyl derivatives; 2-amino-1,2,3,4,-tetrahydro-6-methoxy- 2-naphthoic acid and the corresponding 7- ethoxy and 3,6-dimethyl derivative. A pharmaceutical composition comprises a penicillin of Formula I or a salt thereof and a carrier.