Christopher M. Cimarusti

4-Alkylated monobactams : Chiral synthesis and antibacterial activity

Abstract The synthesis of 4-alkylated monobactams by a variety of procedures is described. Two complementary procedures have been developed for the chiral synthesis of rnonobactams. (1) sulfonation of 4-alkyl-3-(protected)amino-2-azetidinones with vanous complexes of SO3, and (2) cyclization of β mesyloxyacyl sulfamates derived from β-alkyl-β-hydroxy-α-amino acids The most general procedure involves introduction of the alkyl group via a Grignard reaction on 6-APA-derived sulfones 23 or 24 followed by sulfonation. For the specific case of (3S,trans)-3-amino-4-methylmonobactamic acid (48). cyclization of the β-mesyloxyacyl sulfamate 40 derived from (L)-threonine is the preferred route. The introduction of 4-alkyl groups into monobactams results in a decrease in activity against gram-positive bacteria, an increase in activity against gram-negative bacteria, and an increase in β-lactamase stability. Increasing the size of the alkyl group beyond methyl results in diminished intrinsic antibacterial activity. 4β-Alkylmonobactams display better β-lactamase stability than their 4α-counterparts.

7-[2-hydroxyethyl] cephalosporanic acid derivatives

The preparation of cis and trans 7-[2-hydroxyethyl] cephalosporanic acid salts, as well as their corresponding O-sulfate analogs, is described. A very useful method for preparing large quantities of 7-oxocephalosporanates from 7-ACA is also described.

An a-nor-3-thia-5β-pregnane

Abstract The conversion of a 5β-pregnan-3-one into a 3-thia-A-nor-pregnane is described. The single epimer, characterized as the 5β-isomer by nmr spectroscopy, was obtained. A previous report [1] from this laboratory described the synthesis of the epimeric 3-oxa-A-norpregnan-20-ones 1 and 2 from A-norprogesterone. Recently, the total synthesis of the related A-nor-3-thiaestra-1,-5(10)-diene derivative 3 has been described [2]. Continuing interest [3] in A-ring-modified steroids as probes of drug-receptor interactions prompts this report of the preparation of the 3-thia-5β-A-norpregnan-20-one 4 .

Photooxidation of 1-acetoxy-3,5-cycloheptadiene

Abstract A method for the preparation of cis oxygenated cycloheptyl systems has been developed. Photooxidation of 3 gives mainly 4 , resulting from attack syn to the acetoxy substituent. The acetate function of both 4 and 5 , the minor anti-product, appears to affect the rate of endoperoxide to diepoxide rearrangement.

Deacylation of amides: removal of the acyl side-chain from cephamycin derivatives

Diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)thio]methyl}-Δ3-cephem-4-carboxylate (9) is obtained from a cephamycin C derivative by treatment of an imino chloride intermediate with o-aminobenzenethiol.