Studies related to penicillins. Part XVI. Preparation of methyl 2-{(1S,5R)-3-benzyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl}-3-methylbut-2-enoate

Abstract

Acetoxymercury(II)(2S)-3-acetoxymercurio(II)thio-2-{(1S,5R)-3-benzyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]-hept-2-en-6-yl}-3-methylbutanoate (9) is converted by hydrogen sulphide into the mercaptobutanoic acid (11), which readily rearranges to a mixture of 2-(2-benzyloxazol-4-ylcarbonylamino)-3-mercapto-3-methylbutanoic acid (17), (3S)-2,3,4,7-tetrahydro-2,2-dimethyl-6-phenylacetamido-7-oxo-1,4-thiazepine-3-carboxylic acid (19), and (2S,5S,6S)-2-(1-mercapto-1-methylethyl)-6-phenylacetamido-4-oxa-1-azabicyclo[3.2.0]heptane-3,7-dione (21).

The mercaptobutanoate (10), derived from the acid (11) and diazomethane, reacts with mercury(II) acetate to to give dimethyl 3,3′-mercurio(II)dithiobis-[(2S)-2-{(1S,5R)-3-benzyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]-hept-2-en-6-yl}-3-methylbutanoate](15). Diazomethane transforms the mercaptobutanoate (10) into the methylthio-butanoate (13), which is oxidised to a mixture of sulphoxides (14) by m-chloroperbenzoic acid. Compound (13) is also produced when the potassium salt of the acid (11) is treated with methyl iodide. In dimethyl sulphoxide the potassium salt of the acid (11) isomerises to the potassium salt of the thiazepine (20).

The title compound is produced when the mercaptobutanoate (10) is treated with methanolic sodium methoxide, when the bis(sulphide)(15) is treated with mercury(II) acetate, and when the sulphoxides (14) are heated in benzene.