Design and Synthesis of New 4-Alkylthio Monocyclic β-Lactams

Abstract

New types of monocyclic β-lactams constitute an important class of compounds due to their unique structures and natures. Here, the design and synthesis of new 4-alkylthio monocyclic β-lactams 2a and 3a are reported. Significantly, compounds 2a and 3a, while keeping a monocyclic system, were designed to contain all of the substructures provided by the cleavage of C(2)-C(3) bond in penicillins. Efficient synthetic pathways for compounds 2a and 3a were established based on two different strategies. Compound 2a was synthesized from raw materials, using 4-acetoxyazetidin-2-one as a key intermediate, through a ten-step synthetic sequence in 3% overall yield. Compound 3a was synthesized from potassium salt of penicillin G (17), using the degraded product 20 as a key intermediate, through a six-step synthetic sequence in 11% overall yield. 4-Alkylthioazetidin-2-one derivatives, introduced in this study, could serve as valuable intermediates for the development of new monocyclic β-lactams.

Advances in synthesis of monocyclic beta-lactams

“…81 After in situ reductive removal of the chlorosulfonyl group from the 2-azetidinone 151, the resulting 2-azetidinone 152 was thioalkylated using sodium isopropylthiolate 153 to yield the 2-azetidinone 154.…”