Synthesis of 6-methylthiopenicillins and 7-heteroatom-substituted cephalosporins

Abstract

B. From the Aldehyde 6.-A solution of 0.51 g (1.0 mmol) of 6, 0.13 g (1.0 mmol) of sodium thiophenoxide,14 and 1.0 ml of N,N-dimethylformamide was stirred for 40 min. Water (25 ml) was added and the resulting mixture was extracted with 3 X 10 ml of methylene chloride. The methylene chloride solution was washed with 2 X 7 ml of water and dried. The solvent was evaporated and residual oil was chromatographed on a silicic acid (100 mesh) column with ethyl acetate. The effluent was separated into a homogeneous fraction which crystallized from a mixture of benzene and petroleum ether after a seed of the phenylthioazetidinone 9 was added, 87.6 mg (19.9%), tic Rt was iden-

An Alternative Method for the Synthesis of S-Methylmethanethiosulfonate

“…The 1 H NMR of this compound shows two peaks as singlet at 2.71 and 3.32 ppm corresponding to chemically two different methyl groups indicating that the two methyl groups are low field shifted compared to DMSO which shows a single peak at 2.62 ppm. Similarly, 13 C NMR spectrum of 2 shows two peaks at 18.2 and 48.8 ppm corresponding to two different methyl groups and non-decoupled 13C-nmr spectrum further shows two methyl carbon as quartet indicating the presence of three coupling protons on each carbon atoms. The fragmentation pattern of 2 obtained by EI (30 eV) shows major products corresponding to 126(M+), 111(CH 3 SO 2 S+), 79(CH 3 SO 2 +), 63(CH 3 SO+), and 47(CH 3 S+) respectively.…”

“…In a similar way, a reaction of DMSO in presence of TiCl 4 in 1,2-Dichloroethane resulted in the formation of S-Methylmethanethiosulfonate. S-Methylmethanethiosulfonate is a very useful sulfenylating reagent for organic synthesis as well as for biological applications [6][7][8][9][10][11][12][13][14][15]. Particularly, it is used for introduction of SCH 3 groups in aromatic rings and other organic compounds including biologically active molecules.…”

6.alpha.-Substituted penicillins

“…Benzyl 6-Cyano-6-hydroxypenicillanate (5). Liquid hydrogen cyanide was made according to the method of Vogel.9 It was transferred to a flask containing the oily benzyl 6-oxopenicillanate (2.04 g) and a few crystals of sodium cyanide.…”

Naturally Occurring β-Lactams

“…This was achieved in a completely stereocontrolled manner by a novel substitution method. Thermal introduction of the hydrazo-substituent to form (192) was followed by oxidation and conversion to the trans-hydroxy ester (193). Inversion by displacement of the mesylate with azide and subsequent reduction gave the cis-amino ester (194) which afforded the ~ lactam (195) on cyclisation.…”