Deprotection of p-nitrobenzyl esters and valyl carbamates in carbapenem CL 192,276 produced the active compound OCA-983 in excellent yields. Straight chain alkanols such as 1-butanol, 1-pentanol and 1-hexanol in water at certain ratios were effective solvent systems. Alkyl acetates in water also resulted in simultaneous deprotection of PNB and PNZ side-chains albeit at slower rates. The deprotected carbapenem was isolated in excellent yield and purity after removal of the aqueous media. This procedure is applicable to sensitive compounds that are soluble in water without the need to use a buffer and allows for ease of isolation from the aqueous phase.

The effect of introducing hydrophobic groups onto the disaccharide portion of the mannopeptimycins has been examined. Under acid-catalyzed conditions dimethyl acetals and ketals react on the terminal mannose of the disaccharide moiety of mannopeptimycin-alpha and the cyclohexylalanyl analogue 2. The preferentially formed monofunctionalized 4,6-acetals and -ketals display potent antibacterial activities against Gram-positive microorganisms, including MRSA, PRSP, and VRE pathogens.

Novel ether derivatives of mannopeptimycin glycopeptide were synthesized to probe their SAR. Many of these derivatives exhibited potent antibacterial activity against methicillin resistant and vancomycin resistant strains. These ether derivatives were prepared via reductive ring cleavage of acetals to give a mixture of 6-O, 4-O, 3-O, and 2-O-ether isomers. Both 6-O-ether and 4-O-ether showed significantly enhanced antibacterial activity over the parent and the isovalerate esters.

A series of benzoxazole derivatives of the mannopeptimycin glycopeptide antibiotics was synthesized via a novel benzoxazole formation reaction by treating aminophenol of mannopeptimycin-beta with an aldehyde and DDQ in DMF. Some of these derivatives (e.g., 5b, 5d, 5m, and 7b) showed good activity against Gram-(+) bacteria when compared to the parent compound mannopeptimycin-beta.

A number of 6-O-ether and 4-O-ether derivatives of mannopeptimycin-α with different steric bulk and lipophilicity were synthesized for structure–activity relationship study. Novel iodo and bromo mannopeptimycin-α were also prepared. These compounds were synthesized via electrophilic aromatic substitution. Many of the new ether derivatives exhibited potent antibacterial activity against Gram-positive resistant strains including VRE, MRSA, and PRSP.

A mathematical model, based on reactions of independent functional groups, is derived to describe kinetic resolutions of bifunctional meso/dl stereoisomeric mixtures. The model indicates that only the slow reacting enantiomer can be obtained (as recovered starting material) with high stereoisomeric purity in these processes; the products from the fast reacting enantiomer and the meso diastereomer are predicted to have limited diastereoisomeric purity. Recycling strategies are presented that can serve to enhance the purity of the these products. In particular, if recycling can be performed using a reaction with selectivity opposite to that in the first cycle, it is predicted that all three components of a meso/dl mixture (or their derived products) can be obtained with high stereoisomeric purity, even from a process with modest enantiotopic group selectivity. These predictions were tested by Sharpless epoxidation. of a 1:1 mixture of meso and racemic stereoisomers of 6,6-ethylenedioxy-1,10-undecadiene-3,9-d (1) under conditions of high (40:1) and modest (9:1) selectivity. In both scenarios, the two C-2 enantiomers and the monoepoxide derivative of the meso diastereomer of 1 were obtained with high stereoisomeric purity (greater than or equal to 97% dp, >99% ee) from an initial L-tartarate mediated epoxidation of the mixture followed by recycling of the mono- and diepoxide fractions by deoxygenation (KSeCN) and reepoxidation using a D-tartarate derived catalyst. The results are in reasonable agreement with those calculated with the mathematical model.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPreparation of Desymmetrized Meso Derivatives by Kinetic Resolution of meso/dl Stereoisomeric MixturesDale E. Ward, Yadong Liu, and David HowView Author Information Department of Chemistry, University of Saskatchewan Saskatoon, Saskatchewan S7N 5C9, Canada Cite this: J. Am. Chem. Soc. 1996, 118, 12, 3025–3026Publication Date (Web):March 27, 1996Publication History Received24 October 1995Published online27 March 1996Published inissue 1 January 1996https://doi.org/10.1021/ja953576aCopyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views229Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (242 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Chemical reactions,Materials,Mixtures,Molecular structure,Selectivity Get e-Alerts