Two synthetic strategies leading to the basic skeletons of the title compounds are discussed. The special attention is focused on the problem of stereocontrol in the formation of a desired configuration of the bridgehead carbon atom. The first one involves cycloaddition reaction between vinyl ethers or alkoxyallenes with chlorosulfonyl isocyanate. The second one is based on the nucleophilic substitution at C-4 of the azetidin-2-ones performed as intramolecular process.

[2+2]Cycloaddition of chlorosulfonyl isocyanate to chiral vinyl ethers proceeds with excellent diastereoselectivity whereas the same reaction with chiral alkoxyallenes provides moderate diastereoselectivity. In the latter case, however, the exo double bond next to the β-lactam carbonyl atom can be easily transform into variety of substituents.

The second methodology is based on readily available 4-vinyloxy-azetidin-2-one and allows formation only oxa- and carbacephams. Reaction proceeds via formation of acyliminium cation generated from the β-lactam fragment, which subsequently is trapped by a nucleophile to produce the corresponding bicyclic skeleton. Attempts to form penam skeletons using that waywere, so far,  unsuccessful.

The antibacterial and antifungal properties of all β-lactams obtained were investigated to show, however, moderate activities.

Acknowledgements

This work was supported by a grant PBZ-KBN-126/T09/08/2004 and by a network „Synthesis, structure and therapeutic properties of compounds and organic substances”.

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