76454-56-3Relevant academic research and scientific papers
Process enabling and the scale-up of 6β-hydroxymethylsulbactam and its esters
Norris, Timothy,Ripin, David H. Brown,Ahlijanian, Paul,Andresen, Brian M.,Barrila, Mark T.,Colon-Cruz, Roberto,Couturier, Michel,Hawkins, Joel M.,Loubkina, Ioulia V.,Rutherford, Jennifer,Stickley, Kurt,Wei, Lulin,Vollinga, Roel,De Pater, Robert,Maas, Peter,De Lange, Ben,Callant, Dominique,Konings, Jeroen,Andrien, Jean,Versleijen, Jos,Hulshof, Jos,Daia, Elena,Johnson, Natalka,Sung, David W. L.
, p. 432 - 439 (2012/12/25)
The optimization of the synthesis of 6β-hydroxymethylsulbactam is described. The primary challenge in this synthesis is the installation of the 6β-hydroxymethyl group with the proper stereochemistry. Engineering challenges associated with the addition of gaseous formaldehyde to a Grignard reagent at low temperature and a number of approaches to achieving the appropriate β-stereochemistry are presented.
6-(Aminomethyl)penicillanic acid 1,1-dioxide esters and intermediates therefor
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, (2008/06/13)
6-alpha- and 6-beta-(Aminomethyl)penicillanic acid, 1,1-dioxide esters which are hydrolyzable under physiological conditions, particularly those wherein the ester radical is 1H-isobenzofuran-3-on-1-yl or (5-methyl-1,3-dioxol-2-on-4-yl)methyl, and an improved process and intermediates used in their synthesis.
Beta-lactamase inhibiting 6-(alkoxyamino-methyl) penicillanic acid 1,1-dioxide and derivatives
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, (2008/06/13)
6-alpha/beta-[(C1 -C4)Alkoxyaminomethyl and benzyloxyaminomethyl]penicillanic acid 1,1-dioxides, pharmaceutically acceptable salts thereof and conventional esters thereof hydrolyzable under physiological conditions, all of which are
Process for 6-(aminomethyl)penicillanic acid 1,1-dioxide and derivatives thereof
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, (2008/06/13)
A process for the preparation of beta-lactamase inhibiting 6-alpha-(aminomethyl)penicillanic acid 1,1-dioxide and derivatives. R- and S-1-(ethoxycarbonyloxy)ethyl 6-alpha-(aminomethyl)penicillanate 1,1-dioxide are specifically described.
Process for debromination of dibromopenicillanic acid and derivatives
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, (2008/06/13)
A process for the debromination of 6-monobromo- and 6,6-dibromopenicillanic acid, and various derivatives thereof, by the action of a bisulfite salt. The debrominated compounds produced find various utilities, as beta-lactamase inhibitors useful in therapy in combination with known beta-lactam antibiotics, or as intermediates in the further synthesis of useful beta-lactam compounds.
STEREOSELECTIVE PREPARATION OF 6β-SUBSTITUTED PENICILLANATES. TRI-ORGANOTIN HYDRIDE REDUCTION OF 6-ISOCYANO-, 6-PHENYLSELENENYL-, 6-HALO-, AND 6-ISOTHIOCYANATO-PENICILLANATES
John, D. Ivor,Tyrrell, Nicholas D.,Thomas, Eric J.
, p. 2477 - 2484 (2007/10/02)
6β-Benzyl-, 6β-(2-hydroxyprop-2-yl)-, 6β-methoxycarbonylmethyl-, 6β-methoxycarbonylethyl-, 6β-(t-butoxycarbonylmethyl)-, and 6β-methylthiopenicillanates 10-15 have been prepared stereoselectively by tri-n-butyltin hydride reduction of the corresponding 6β-isocyanopenicillanates 4-9.A minor side-product (15percent) isolated from the reduction of benzyl 6α-(2-hydroxyprop-2-yl)-6β-isocyanopenicillanate 5 was identified as (1R,5R)-6--1-(2-hydroxyprop-2-yl)-2,6-diaza-4-thiabicyclohept-2-en-7-one 18, and small quantities of analogous thiazolines 19 and 20 were detected in the crude mixtures from the reductions of the 6α-benzyl- and 6α-methoxycarbonylmethyl-6β-isocyanopenicillanates 4 and 6.Benzyl and methyl penicillanates 30 and 31 were obtained by tri-n-butyltin hydride reduction of the 6α-brompenicillanates 28 and 29, and reduction of benzyl 6,6-dibromopenicillanate 35 gave a mixture of products in wich the 6β-bromopenicillanate 37 predominated. 6β-Chloro-, 6β-phenylselenenyl-, and 6β-allylpenicillanates 48, 49 and 52 were obtained by tri-n-butyltin hydride reduction of the corresponding 6-phenyl- selenenylpenicillanates 43, 45, 50 and 51. In contrast, tri-organotin hydride reduction of methyl 6β-isothiocyanatopenicillanate 53 was accompanied by sulphur-C(2) bond cleavage to give rearranged thiazoline-azetidinones 54 and 55.
