Synthesis of Various 3-Substituted 1,2,4-Oxadiazole-Containing Chiral β3- and α-Amino Acids from Fmoc-Protected Aspartic Acid
- 21 August 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 68 (19), 7316-7321
- https://doi.org/10.1021/jo0345953
Abstract
Various 3-substituted chiral 1,2,4-oxadiazole-containing Fmoc-beta(3)- and -alpha-amino acids were synthesized from Fmoc-(l or d)-Asp(OtBu)-OH and Fmoc-l-Asp-OtBu, respectively, in three steps (i.e., condensation of an aspartyl derivative with differentially substituted amidoximes, formation of the 1,2,4-oxadiazole, and cleavage of the tert-butyl ester). These compounds represent new series of nonnatural amino acids, which could be used in combinatorial synthesis. A simple protocol has been developed to generate the 1,2,4-oxadiazole ring. Indeed, common methods resulted in cleavage of the Fmoc group or required long reaction times. We found that sodium acetate in refluxing ethanol/water (86 degrees C) was a convenient and efficient catalyst to promote conversion of Fmoc-amino acyl amidoximes to 1,2,4-oxadiazoles, and this procedure proved to be compatible with Fmoc protection. It is shown that these compounds can be prepared without significant loss of enantiomerical purity. Furthermore, the alkaline conditions used to cleave the Fmoc protecting group from these compounds did not induce epimerization of their chiral center.Keywords
This publication has 22 references indexed in Scilit:
- Parallel synthesis of 1,2,4-oxadiazoles from carboxylic acids using an improved, uronium-based, activationTetrahedron Letters, 2001
- Oxadiazoles as bioisosteric transformations of carboxylic functionalities. IIEuropean Journal of Medicinal Chemistry, 1996
- Amide and α-keto carbonyl inhibitors of thrombin based on arginine and lysine: Synthesis, stability and biological characterizationBioorganic & Medicinal Chemistry, 1995
- Synthesis of 1,2,4-Oxadiazole-, 1,3,4-Oxadiazole-, and 1,2,4-Triazole-Derived DipeptidomimeticsThe Journal of Organic Chemistry, 1995
- Oxadiazoles as bioisosteric transformations of carboxylic functionalities. Part IEuropean Journal of Medicinal Chemistry, 1994
- Stereospecific Synthesis of Peptidyl .alpha.-Keto Amides as Inhibitors of CalpainJournal of Medicinal Chemistry, 1994
- Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus ActivityJournal of Medicinal Chemistry, 1994
- Inhibition studies of some serine and thiol proteinases by new leupeptin analogsJournal of Medicinal Chemistry, 1993
- Convenient preparation of (9-fluorenyl)methanol and its 2,7-dihalo derivativesThe Journal of Organic Chemistry, 1980
- Synthèse de deux nouveaux acides amines phénoliques comportant un cycle 1,2,4-oxadiazoleHelvetica Chimica Acta, 1977