A short and high-yielding synthesis of optically active 3-aminonocardicinic acid (3-ANA) is described. The fourth component condensation reaction of N2-protected l-2,3-diaminopropanoic acid with p-benzyloxybenzaldehyde and butyl isocyanide gave directly the amide derivatives of 3-ANA, as a diastereomeric mixture, which was, after conversion of the amide group into the benzhydryl ester, led in good yield to a single disatereomer with natural chirality via epimerization. Deprotection of the 3-ANA derivative gave 3-ANA.

The synthesis and antibacterial activity of 3-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)-acetamido]-2-azetidinone-l-sulfonic acid derivatives with a heteroatom-bound substituent at the 4-position are described. The effect of various 4-substituents on the antibacterial activity was examined. Some of these compounds showed excellent antibacterial activity especially against Gram-negative bacteria, including 63-lactamase-producing strains.Our earlier chemical modification of sulfazecinl,=' revealed that although some of the 4-unsubstituted 2-azetidinone-l-sulfonic acid derivatives with various 3-acylamino groups had improved antibacterial activity, these compounds generally lack the activity against 3-lactamase-producing strains.To correct for this deficiency we explored new derivatives having various 4-heteroatom-bound substituents". This paper deals with the synthesis and the antibacterial activity of 3-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)acetamido]-2-azetidinone-l-sulfonic acid derivatives with 4-heteroatombound substituents. ChemistryReactions of the 4;3-methylsulfonyl compound (2Bb)°', or the 4a-acetoxy compound (2Aa) which is obtainable by hydrogenolysis of 3-benzyloxycarbonylamino derivative (1)°,-'' over Pd-black followed by tritylation with trityl chloride and triethylamine, with various nucleophiles (Y-) gave mixtures of the 4a-substituted-2-azetidinone derivatives (2Ac-h) and the 4,3-isomers (2Bc'h).The 4-methoxycarbonyllnethylthio derivatives (2Ae and 2Be) were converted into 4-carbamoylmethylthio derivatives (2Ai and 2Bi) by treatment with ammonia, and the 4,3-azido compound (2Bh) was transformed to the 4,3-triazolyl compounds (2Bj and 2Bk) by the 1,3-dipolar cycloaddition reactions' with methyl propiolate. 3-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-4-substituted -2-azetidinone-l-sulfonic acid derivatives (7a -k) were synthesized from these 3-tritylamino compounds (2A and 2B) as shown in Chart 2.

The title compounds have been synthesized from N-protected l-aspartic acid via Curtius rearrangement.

Die Propionsäuren (I) reagieren mit dem Aldehyd (II) und dem Isocyanid (III) zu ca. 1 :l‐Gemischen der diastereomeren Azitidinone (IV) und (V).

Aus dem Penicillin‐Derivat (I) wird das monocyclische lS‐Lactam (III) hergestellt.