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

Abstract

Sang Hyup LeeCollege of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea. E-mail: sanghyup@duksung.ac.krReceived August 1, 2012, Accepted October 16, 2012New types of monocyclic β-lactams constitute an important class of compounds due to their unique structuresand 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 thesubstructures provided by the cleavage of C(2)-C(3) bond in penicillins. Efficient synthetic pathways forcompounds 2a and 3a were established based on two different strategies. Compound 2a was synthesized fromraw materials, using 4-acetoxyazetidin-2-one as a key intermediate, through a ten-step synthetic sequence in3% overall yield. Compound 3a was synthesized from potassium salt of penicillin G (17), using the degradedproduct 20 as a key intermediate, through a six-step synthetic sequence in 11% overall yield. 4-Alkylthio-azetidin-2-one derivatives, introduced in this study, could serve as valuable intermediates for the developmentof new monocyclic β-lactams. Key Words : Monocyclic β-lactams, Penicillin, Isopropylthioazetidinone, t-Butylthioazetidinone, Degrada-tion of penicillin IntroductionThe four-membered ring appears to be the smallest cyclicsystem that accommodates the amide function as a con-stituent. Such four-membered cyclic amides, commonly re-ferred to β-lactams, possess physical and chemical pro-perties that diverge sharply from those of acyclic amides,partially due to ring strain. After numerous penicillins andcephalosporins, new types of nonclassical β-lactams haveappeared. Monocyclic β-lactam compounds