title: Solid-Phase Synthesis of ɤ-Lactone and 1,2-Oxazine Derivatives and Their Efficient Chiral Analysis.
abstract: Derivatives of 3-methyl-3,6-dihydro-2H-1,2-oxazine-6-carboxylic acid prepared by regioselective hetero Diels-Alder reaction of arylnitroso compounds with sorbic acid were used for solid-phase synthesis of a library of derivatives that included modification of carboxylic group, dihydroxylation of double bond and cleavage of N-O bond. Derivatives of 2,3,4-trihydroxyhexanoic acid obtained from 3,6-dihydro-2H-1,2-oxazines after double bond dihydroxylation and N-O cleavage were used for simple and stereoselective formation of chiral lactones derived from 3,4-dihydroxydihydrofuran-2(3H)-one. The final compounds obtained as a mixture of stereoisomers were analyzed with use of chiral HPLC and SFC. HPLC analyses were not successful for all derivatives or required lengthy chromatography. On the other hand SFC afforded much shorter analyses and was effective for all studied derivatives. The method of synthesis and analysis is thus suitable for future study of stereoselective synthesis of lactones and other derivatives from single oxazine derivatives and application of high-throughput synthesis on solid-support and combinatorial chemistry.
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Sona
authors.initials: S
authors.lastname: Krupkova
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Gonzalo Pazos
authors.initials: GP
authors.lastname: Aguete
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Leona
authors.initials: L
authors.lastname: Kocmanova
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Volna
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Grepl
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Novakova
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, IN, United States of America.
authors.forename: Marvin John
authors.initials: MJ
authors.lastname: Miller
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hlavac
mesh_terms: D002851:Chromatography, High Pressure Liquid; D061565:Cycloaddition Reaction; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism
chemical_list: D007783:Lactones; D010078:Oxazines