25451-53-0Relevant academic research and scientific papers
A facile, one-pot procedure for the preparation of 2-phenyl-1,3-propanediol monocarbamate, a metabolite of felbamate
Miller, Thomas A.,Dieckhaus, Christine M.,Macdonald, Timothy L.
, p. 611 - 612 (2000)
A simple, one-pot procedure for the preparation of 2-phenyl-1,3-propanediol monocarbamate (MCF) has been developed. This procedure represents the most efficient method for preparing MCF published to date, and it is amenable to the large-scale laboratory production of this biologically relevant metabolite of felbamate.
Catalytic One-Pot Oxetane to Carbamate Conversions: Formal Synthesis of Drug Relevant Molecules
Guo, Wusheng,Laserna, Victor,Rintjema, Jeroen,Kleij, Arjan W.
, p. 1602 - 1607 (2016/10/13)
Oxetanes are versatile building blocks in drug-related synthesis to induce property-modulating effects. Whereas related oxiranes are widely used in coupling chemistry with carbon dioxide (CO2) to afford value-added commodity chemicals, oxetane/CO2couplings remain extremely limited despite the recent advances in the synthesis of these four-membered heterocycles. Here we report an effective one-pot three-component reaction (3CR) strategy for the coupling of (substituted) oxetanes, amines and CO2to afford a variety of functionalized carbamates with excellent chemoselectivity and good yields. The process is mediated by an aluminium-based catalyst under relatively mild conditions and the developed catalytic methodology can be applied to the formal synthesis of two pharmaceutically relevant carbamates with the 3CR being a key step. (Figure presented.).
Methods for synthesis of dicarbamate compounds and intermediates in the formation thereof
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Page/Page column 8, (2008/06/13)
Disclosed is a method of making 2-substituted-2-halo-1,3-propanediols via reduction of corresponding malonate compounds. Also disclosed is a method of making 2-substituted-2-halo-1,3-dicarbamate compounds (such as halo derivatives of felbamate, including fluorofelbamate) via reduction of malonate compounds, followed by carbamoylation. Reduction of the malonate compounds is carried out using an electrophilic hydride reagent.
Identification of modified atropaldehyde mercapturic acids in rat and human urine after felbamate administration
Thompson, Charles D.,Gulden, Pamela H.,Macdonald, Timothy L.
, p. 457 - 462 (2007/10/03)
3-Carbamoyl-2-phenylpropionaldehyde has recently been proposed [Thompson et al. (1996) Chem. Res. Toxicol. 9, 1225-1229] as a potential reactive metabolite of the anti-epileptic drug felbamate. This aldehyde was found to undergo rapid elimination to generate 2-phenylpropenal and reversible cyclization to generate 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one at physiological pH. 2-Phenylpropenal, an α,β-unsaturated aldehyde commonly termed atropaldehyde, is a potent electrophile and undergoes rapid conjugation with glutathione. We sought to demonstrate the formation of atropaldehyde in vivo through the identification of mercapturic acids in rat and human urine after felbamate administration. In this paper, we describe the identification of both the reduced (N-acetyl-S-(2-phenylpropan-3-ol)-L- cysteine) and oxidized (N-acetyl-S-(2-phenyl-3-propanoic acid)-L-cysteine) mercapturic acids of atropaldehyde in rat and human urine. The reduced species was the more abundant in human (~2:1) and rat (~6:1) urine. These findings establish the possibility that atropaldehyde is formed from felbamate in vivo, undergoes glutathione conjugation, and is ultimately excreted in urine in the form of mercapturic acids. Thus, the proposed pathway of felbamate biotransformation, if confirmed in patients, could contribute to our understanding of the toxicities observed during felbamate treatment.
