title: Stereoselective Polymer-Supported Synthesis of Morpholine- and Thiomorpholine-3-carboxylic Acid Derivatives.
abstract: Herein we report the polymer-supported synthesis of 3,4-dihydro-2H-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH as the starting materials. After the solid-phase-synthesis of N-alkyl-N-sulfonyl/acyl intermediates, the target dihydrooxazines were obtained using trifluoroacetic acid-mediated cleavage from the resin. This approach was also studied for the preparation of dihydrothiazines from immobilized Fmoc-Cys(Trt)-OH. Inclusion of triethylsilane in the cleavage cocktail resulted in the stereoselective formation of the corresponding morpholine/thiomorpholine-3-carboxylic acids. Stereochemical studies revealed the specific configuration of the newly formed stereocenter and also the formation of stable N-acylmorpholine rotamers.
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacký University , 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Králová
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacký University , Hněvotínská 5, 779 00 Olomouc, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fülöpová
authors.affiliation: JEOL Resonance Inc. , Musashino 3-1-2, Akishima, Tokyo 196-8558, Japan.
authors.forename: Michal
authors.initials: M
authors.lastname: Maloň
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacký University , 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Volná
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacký University , 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Popa
authors.affiliation: Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacký University , Hněvotínská 5, 779 00 Olomouc, Czech Republic.
authors.forename: Miroslav
authors.identifier: 0000-0001-7288-8617
authors.initials: M
authors.lastname: Soural
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013237:Stereoisomerism; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D002264:Carboxylic Acids; D005449:Fluorenes; D009025:Morpholines; D010078:Oxazines; D011108:Polymers; D013843:Thiazines; C028971:thiamorpholine
keywords: amino acid; bromoketone; morpholine; nitrobenzenesulfonyl chloride; oxazine; solid-phase synthesis; stereoselective synthesis; thiazine; thiomorpholine