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.
- MeSH
- cykloadiční reakce MeSH
- hmotnostní spektrometrie MeSH
- laktony chemická syntéza chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- oxaziny chemická syntéza chemie MeSH
- stereoizomerie MeSH
- techniky syntézy na pevné fázi MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
4-Chloro-2-fluoro-5-nitrobenzoic acid is a commercially available multireactive building block that can serve as a starting material in heterocyclic oriented synthesis (HOS) leading to various condensed nitrogenous cycles. This work describes its ability for the preparation of substituted nitrogenous heterocycles having 5-7-membered cycles via polymer-supported o-phenylendiamines. Immobilization of this compound on Rink resin followed by further chlorine substitution, reduction of a nitro group and appropriate cyclization afforded benzimidazoles, benzotriazoles, quinoxalinones, benzodiazepinediones and succinimides. The method developed is suitable for the synthesis of diverse libraries including the mentioned types of heterocycles, which have significant importance in current drug discovery. In this paper, we also report limitation of these method and unsuccessful attempt to prepare an 8-membered benzodiazocine cycle.
- MeSH
- dítě MeSH
- dospělí MeSH
- komorbidita MeSH
- komplikace těhotenství imunologie krev MeSH
- plod MeSH
- porod MeSH
- prenatální poškození etiologie prevence a kontrola MeSH
- Sjögrenův syndrom * diagnóza etiologie patofyziologie terapie MeSH
- slinné žlázy patologie MeSH
- slzné ústrojí patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- O autorovi
- Sjögren, Henrik, 1899-1986 Autorita
