合成路线1

1) The reaction of L-aspartic acid (I) with NaNO2, NaBr and H2SO4 gives 2(S)-bromosuccinic acid (II), which is reduced with methyl sulfide borane complex in THF, yielding 2(S)-bromobutane-1,4-diol (III). The cyclization of (III) with Cs2CO3 in methylene chloride affords (R)-(2-hydroxyethyl)oxirane (IV), which is acylated with methanesulfonyl chloride to the corresponding mesylate (V). The cyclization of (V) with Na2S in acetonitrile/water gives 3(R)-hydroxythiolane (VI), which is acylated with p-toluenesulfonyl chloride, affording the corresponding tosylate (VII). The controlled oxidation of (VII) with potassium peroxymonosulfate (oxone) gives 3(R)-(p-toluenesulfonyloxy)thiolane-1(R)-oxide (VIII), which by reaction with potassium thioacetate in acetone is converted to 3(S)-(acetylthio)thiolane 1(R)-oxide (IX). The reaction of (IX) with NaOEt and CS2 in ethanol yields the trithiocarbonate (X), which is condensed with the chloroazetidinone (XI), yielding the trithiocarbonate ester (XII). The condensation of (XII) with 2-chloroallyloxalyl fluoride (XIII) by means of diisopropylethylamine in methylene chloride affords the substituted oxalamic ester (XIV), which is cyclized by means of triethyl phosphite in refluxing chloroform to the fully protected penem derivative (XV). The reaction of (XV) with tetrabutylammonium fluoride (TBAF) in THF eliminates the protecting tert-butyldimethylsilyl group, yielding the chloroallyl ester (XVI), which is treated with triphenylphosphine and sodium 2-ethylhexanoate in dichloromethane to obtain the corresponding sodium salt (XVII). Finally, this compound is treated with HCl in cool water.