Penicillins

1,184,665. Penicillins; phosphorus esterchlorides. ASTRA A.B. 8 Dec., 1967 [28 Dec., 1966; 29 March, 1967], Nos. 57987/66 and 14332/67. Headings C2A and C2C. The invention comprises phosphinylamino and phosphinothiolylamino penicillins of general Formula I and non-toxic salts thereof, wherein APA is the residue R1 is H, or a C 1-5 alkyl, C 1 to C 10 aralkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic heterocyclic group; R2 is R4 or OR4, wherein R4 is H, or a C 1-5 alkyl, C 1-10 aralkyl, monocyclic or bicyclic aryl or monocyclic heterocyclic group; R3 is H, or a C 1-5 alkyl, C 1-10 aralkyl, monocyclic or bicyclic aryl or monocyclic heterocyclic group; which substituents R1, R3 and R4 may be substituted; X and X1 are O or S, at least one of X and X1 being O; and R3 and R4 may be connected and internally form a ring. The penicillins are prepared by reacting an amino penicillin of formula with (A) a compound of formula wherein R1, R2, R3, X and X1 have the above meaning and Z is an atom (or group of atoms) which can be split off together with one of the hydrogen atoms of the amino group of the amino-penicillin to produce penicillins of Formula I; or with (B) a compound of formula wherein R1, R2 and X have the above meaning except that R2 is not H and Z1 gives OH on hydrolysis e.g. is Cl or phenoxy; or with (C) a compound of formula wherein R1 and Z have the above meaning, R5 is R7 or OR7 and R7 is C 1-5 alkyl, monocyclic or bicyclic aryl or monocyclic heterocyclic, which may be substituted, R6 is a group such as benzyl or phenyl which can be cleaved hydrogenolytirally ; or with (D) a compound of formula in which R1, R6 and Z have the above meanings. Alternatively, a 6-aminopenicillanic acid or a salt or derivative thereof of formula is acylated with a compound of formula wherein R1, X and X1 have the above meaning, R8 and R9 are the same or different and are C 1-5 alkyl, C 1-10 aralkyl, monocyclic or bicyclic aryl or monocyclic heterocyclic, which may be substituted, or may form a ring; Y is H or, at the same time as R10, is a di- or tri-alkylsilyl group, R10 is H, a cation, dialkylsilyl, trialkylsilyl, trialkyltin, phenacyl which may be substituted; and COZ2 is an acid chloride or its functional equivalent. Typical compounds are 6-[D-α- (hydroxymethoxyphosphinyl amino) phenylacetamido] penicillanic acid and 6-[D-α-(methoxyphenylphosphinothiolylamino) -phenyl - acetamido penicillanic] acid. Benzyloxy (methoxy)-phosphinyl chloride is prepared by treati