Regioselective Activation of Aminothiazole(iminoxyacetic acid)acetic Acid:  An Efficient Synthesis of the Monobactam Aztreonam

Abstract

An efficient synthesis of the monobactam aztreonam [[2S-[2r,3β(Z)]]-3[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-methyl-4-oxo-1-azetidinesulfonic acid] (1) by acylation of r-aminoazetidinone 22 with the regioselectively activated aminothiazoleiminoxyacetic diacid 15 or 18 is described. Reaction of benzhydryl ester 10 with N-hydroxybenzotriazole and dicyclohexylcarbodiimide followed by ester deprotection formed the monoacid amide 15. Alternatively, chemoselective transient silylation of the diacid 9 followed by activation with N-hydroxysuccinimide formed active ester 18. Acylation of r-aminoazetidinone 22 with amide 15 or ester 18 produced aztreonam (1) in 75-85% yield.

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

“…Even though the text describes the use of this reagent for amide bond formation, it was not included in the experimental protocol. In combination with DCC as well, two examples have been reported in which the OSu esters were isolated prior to the aminolysis step. , HOSu is shelf-stable, and the reagent forms a hydroxylamine ester that can be isolated and is more reactive toward aminolysis. However, because of its hydroxamic acid structure, the reagent can undergo Lossen rearrangement and generate related impurities.…”

“… General remarks: DCC is one of the oldest and most traditional reagents for peptide coupling, but it has been superseded by more practical reagents such as EDCI. Nevertheless, it still comes second to EDCI and surpasses DIC in large-scale applications. ,,,,,,,,, Acid activation with DCC to afford the corresponding O -acylisourea is very fast in solvents with low dielectric constant such as DCM but slower in more polar solvents such as DMF . One of the major drawbacks to the use of DCC is the lack of solubility of the urea byproduct and the difficulty of purging it.…”

5-Carboxytetramethylrhodamine-Ampicillin Fluorescence Anisotropy-Based Assay of Escherichia coli Penicillin-Binding Protein 2 Transpeptidase Inhibition

“…Tebipenem was from BOC Sciences (Shirley, NY). Tigemonam was prepared by Pharmaron (Irvine, CA) according to published routes . ETX2514 was prepared as described previously .…”

“…Tigemonam was prepared by Pharmaron (Irvine, CA) according to published routes. 20 ETX2514 was prepared as described previously. 6 Bodipy FL Nhydroxysuccinimide (NHS) ester was from BroadPharm (San Diego, CA).…”

Visible-Light-Mediated Strategies for the Preparation of Oxime Ethers Derived from O–H Insertions of Oximes into Aryldiazoacetates

“…Oxime ethers are arguably a more elusive class of organic molecules when compared with others (e.g., aldehydes, ketones, carboxylic acids, amines, or olefins). Nevertheless, this unusual class of ethers display a rich panorama of chemical reactivity of their own, being employed in powerful synthetic methods, such as reductions, additions, eliminations, cyclizations, and rearrangements, and numerous molecules containing the oxime ether motif have been studied in the context of a variety of biological activities, such as the treatment of diseases caused by obesity or dyslipidemia ( 1 ), and applications like insecticides/acaricides ( 2 ), herbicides ( 3 ), antimicrobials ( 4 ,) and antibiotics ( 5 and 6 ) (Figure ).…”