Synthesis of 6-hydroxypenicillanates and 7-hydroxycephalosporanates

Abstract

Benzyl 6-oxopenicillanate1-3 has been shown to be a useful intermediate for the synthesis of novel d-lactam antibiotics. One precursor for this compound is benzyl 6o-hydroxypenicillanate (6a), derived from benzyl 6-diazopenicillanate (5a) (Chart I). Syntheses of 5a have been Chart I 3. R2 = C6H50 4, R, = C6H5 a CH,C6H5 b caca c CH.COCcHjOCHj-p d CH(C6H,)2

Reactions of 2,2,2-trichloroethyl 6-diazopenicillanate with aromatic aldehydes. X-Ray crystal structures of (3S,8aS)-2,2,2-trichloroethyl 2,3-dihydro-6-(4-methoxyphenyl)-2,2-dimethyl-5-oxo-5H,8aH-thiazolo[2,3-b][1,3]oxazine-3-carboxylate and (2S,5S)-2,2,2-trichloroethyl-4-formyl-2-(4-methoxyphenyl)-6,6-dimethyl-3-oxotetrahydro-1,4-thiazine-5-carboxylate

“…Lewis Acid-catalysed Reactions with Aromatic Aldehydes.-Addition of a catalytic quantity of boron trifluoridediethyl ether to a solution of the diazopenicillanate (i) 6 and an aromatic aldehyde in dichloromethane at &-5 "C caused nitrogen evolution. From the reaction with 4-methoxybenzaldehyde, the oxazinone (5) (4 1%) was isolated after chromatography, in…”

“…(CHCl3) 1 785,l 760,l 520, and 1 345 cm-'; G,(CDCl,) 1.42 and 1.57 (each 3 H, s, Me), 4 Arc), 138.98 and 148.51 (s, Arc), and 165.7 and 170.10 (s, GO). (6) (85 mg, 13%), m.p. 157-160 "C from CH,Cl,-light petroleum (lit.,5 amorphous powder) (Found: M', 479.9714.…”

“…Chromatography on silica, using ethyl acetate-light petroleum (1 : 9) as eluant, gave three fractions. The first eluted product was identified as (62)-2,2,2-trichloroethyl 6 With ethyl chloroformate. Crude 6a-acetylpenicillanate (12) from 6-diazopenicillanate (1) (220 mg, 0.6 mmol) was treated with ethyl chloroformate (0.68 ml, 0.65 mmol) and triethylamine (66 mg, 0.65 mmol) in dichloromethane (10 ml) as described above.…”

“…Two products were isolated by chromatography using ethyl acetate-hexane (1 : 9), as eluant. The first eluted product was identified as (6Z)-2,2,2-trichloroethyl 6…”

Preparation and properties of substituted 6β-vinylpenicillanic acids

“…The route to compounds (3) and (4) involved initial nitrosation of the trichloroethyl ester of penicillin V (8) with dinitrogen tetroxide, followed by heating it, either in dichloromethane containing pyridine,' or, in better yield, without the pyridine, to give the 6-diazo-derivative (9). Using the method of Giddings et the diazo-ester (9) could be treated with either substituted allylic sulphides or selenides.…”