Studies related to penicillins. Part XIII. Transformations of methyl α-[(2R,3R)-1-(2-hydroxy-2-methylpropionyl)-4-oxo-3-phenoxyacetamidoazetidin-2-ylthio]acetate

Abstract

Methyl α-[(2R,3R)-1-(2-hydroxy-2-methylpropionyl)-4-oxo-3-phenoxyacetamidoazetidin-2-ylthio]acetate (3) is converted into a mixture of dimethyl 2,2′-dithiodiacetate (8) and methyl 3-(2-hydroxy-2-methylpropionamido)-2-phenoxyacetamidoacrylates (12) and (15) by sodium methoxide. Methyl (2R,3R)-3-(2-hydroxy-2-methylpropionamido)-3-methoxycarbonylmethylthio-2-phenoxyacetamidopropionate (17) is an intermediate in the reaction. Ammonia cleaves the β-lactam bond of the azetidinone (3) to give the amide (18); corresponding reactions occur with hydrazine, with methylamine, and with ethylamine to yield derivatives (19)–(21), respectively. In addition to the amide (22), the (E)-acryloylthioacetate (16) is formed when the azetidinone (3) is treated with t-butylamine; the derivative (16) rearranges to the Z-isomer (13) under the reaction conditions. Diethylamine and triethylamine convert the azetidinone (3) into the (Z)-acryloylthioacetate (13).

Methyl α-[(2R,3R)-1-(2-acetoxy-2-methylpropionyl)-4-oxo-3-phenoxyacetamidoazetidin-2-ylthio]acetate (4), formed from the reaction of the alcohol (3) with isopropenyl acetate and toluene-p-sulphonic acid, is transformed into the (Z)-acryloylthioacetate (14) by sodium methoxide, by t-butylamine, and by triethylamine and into the amides (23) and (24) by methylamine and by ethylamine, respectively.

The sulphoxides (27), prepared by oxidation with m-chloroperbenzoic acid of the sulphide (3), are converted into the disulphide (8) and into 2,2-dimethyl-6-phenoxyacetamido-1,4-oxazepine-3(2H),7(4H)-dione (28) by triethylamine.