The structure of an anhydrate form of ampicillin, C16H19N3045, has been determined. \Ct --C,H c--CH3EJ 02 &-coo-It crystallizes in the monoclinic system in space group P2t with two molecules in a unit cell of dimensions a= 12.40, b=6.20, c= 12.00/~, ,8=114"5 ° (standard deviation 0.30%). The structure was solved by Patterson heavy-atom methods and Fourier refinement from X-ray intensity measurements obtained from visual comparison and the equi-inclination Weissenberg method. Full-matrix least-squares refinement yielded an R value of 0.106 for observed data. The molecular configuration is very similar to the known configuration of the trihydrate form (space group P212121). Both forms exist in the crystalline state as zwitterions with hydrogen bonding between the amino nitrogen atom and the ionized carboxyl group. In both forms the thiazolidine ring is puckered with four of the atoms forming an approximately planar arrangement with the remaining atom significantly out of this plane. The non-coplanar atoms are C(2) in the anhydrate and S(1) in the trihydrate. A comparison is made with the known thiazolidine ring configurations of other penicillins. The nitrogen atom N(4) of the,8-1actam of both forms exists in a pyramidal configuration with its neighbouring atoms. The molecular packing of the two forms is completely different. The amino group in the anhydrate is hydrogen bonded to the ionized carboxyl groups of two molecules. In the trihydrate the amino group is hydrogen bonded to a single carboxyl group and to an intricate arrangement of the three hydrogen-bonded water molecules which also form hydrogen bonds to three other atoms within the molecule. There is no further hydrogen bonding in the anhydrate structure.

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N.m.r. and c.d. spectra of some isomeric pairs of penicillins derived from disubstituted acetic acids are reported. For those penicillins which have an aromatic group attached to C-10 empirical correlations are observed between the configuration at C-10 and, (a) the sign of a c.d. band at 200-210 nm, and (b) the chemical shift of the 3-H and methyl protons. These correlations are used to assign the R configuration to the crystalline methyl (3) and ethyl (4) esters of carbenicillin and to the calcium insoluble isomers of carbenicillin (8) and ticarcillin (9). Many of the penicillins show an upfield shift of the methyl protons relative to their position in 6-aminopenicillanic acid ( 16). This is ascribed to shielding effects of the side-chain aromatic ring produced by folded conformations of the side-chain. For the penicillins ( 14) and ( 15) derived from tyrosine, side-chain rotamer proportions calculated from coupling constants are discussed in relation to chemical shifts. Bands at about 230 and 260-280 nm in the c.d. spectra are discussed in comparison with previous c.d. studies of penicillins and the relevant side-chain acids.

The preparation and C-6 epimerisation of benzyl 6a-isocyanopenicillanate is described. By utilising the activating influence of the isocyanide group and a subsequent conversion of this group into an amino-group under mild conditions, 6a-substituted penicillins were thereby prepared. Additionally, several novel rearrangements of these isocyanides are described.1 Glaxo Laboratories Ltd., in German Offenlegungsschrift 2,337,105, 1972, disclose the synthesis of several 7-isocyano-cepl~alosporins and their reaction with aldehydes.* For other stereospecific reactions, electrophilic and nucleophilic, a t C-6 (C-7) in penicillin and cephalosporin derivatives, see ref. 2.