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Stereospecific synthesis, 1 H and 13 C NMR spectroscopy, and X-ray crystallographic studies of 6,6-dibromo-3α-cyano-2,2-dimethylpenam-(1 R )- S -oxide

1991; NRC Research Press; Volume: 69; Issue: 3 Linguagem: Inglês

10.1139/v91-087

1480-3291

Claudio J. Salomón, Oreste A. Mascaretti, Charles E. Strouse, G. Punte,

Metal complexes synthesis and properties

A stereospecific synthesis of 6,6-dibromo-3α-cyano-2,2-dimethylpenam-(1R)-S-oxide (2) is described. The X-ray single crystal investigation of this compound shows that it crystallizes in the monoclinic system, space group P2 1 , with cell parameters a = 6.194(1), b = 9.363(1), c = 9.869(1) Å, β = 96.55(2)°, V = 568(1) Å 3 , and two molecules per unit cell. Thestructure was solved, from low temperature data, by direct methods, and refined, by least-squares procedures, to a final R = 3.17%, R w = 3.38%, for 1221 observed independent reflections. The sulfoxide configuration is R. The thiazolidine presents an envelope shape with the C(3) atom 0.56 Å above the other four members of the ring mean plane. Therefore, it exhibits the conformation with α-CH 3 pseudoequatorial and β-CH 3 and α-CN both pseudoaxial. This conformation is different from the one reported for other penicillin sulfoxide derivatives. The geometry of the β-lactam ring is typical of the fused bicyclic penam nucleus. The ring is non-planar. The N(4) atom displays a pyramidial arrangement. The examination of crystal packing shows that molecules along a are connected by a short C—H … O contactReported single crystal studies showed two dominant conformations for the thiazolidine ring in the fused bicyclic penam nucleus: the C(3) or 2β-3α substituents both pseudoaxial, as found in 2, and the S(1) or 2β-3α substituents both pseudoequatorial, adopted by most sulfoxides. Neither of these conformations can explain the nuclear Overhauser effect data. A conformation with the substituents C2-β-methyl-C3-α-H and C2-α-methyl-C3-α-CN fully eclipsed is in accordance with the experimental results in the solution. The 1 H nuclear magnetic resonance data reflect the influence of the magnetic anisotropy of the CN triple bond on the gem-dimethyl groups, particularly in relation with the geometrical features of the molecule. Comparison of 13 C nuclear magnetic resonance chemical shifts for 2 and its parent penicillin sulfide (1) indicates configurationally dependent substituent effects, the magnitude of which can be used for the stereochemical assignment of sulfoxide groups in this series. Key words: penicillin sulfoxide derivatives, di-halogen penicillanates, stereospecific synthesis, NMR studies, absolute configuration determination.