The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study Научная публикация
| Журнал |
Molecules
ISSN: 1420-3049 |
||||||
|---|---|---|---|---|---|---|---|
| Вых. Данные | Год: 2020, Том: 25, Номер: 16, Номер статьи : 3613, Страниц : DOI: 10.3390/molecules25163613 | ||||||
| Авторы |
|
||||||
| Организации |
|
Реферат:
An efficient asymmetric synthesis of GlaxoSmithKline’s potent PDE4 inhibitor was accomplished in eight steps from a catechol-derived nitroalkene. The key intermediate (3-acyloxymethyl-substituted 1,2-oxazine) was prepared in a straightforward manner by tandem acylation/(3,3)-sigmatropic rearrangement of the corresponding 1,2-oxazine-N-oxide. The latter was assembled by a (4 + 2)-cycloaddition between the suitably substituted nitroalkene and vinyl ether. Facile acetal epimerization at the C-6 position in 1,2-oxazine ring was observed in the course of reduction with NaBH3CN in AcOH. Density functional theory (DFT) calculations suggest that the epimerization may proceed through an unusual tricyclic oxazolo(1,2)oxazinium cation formed via double anchimeric assistance from a distant acyloxy group and the nitrogen atom of the 1,2-oxazine ring.
Библиографическая ссылка:
Pospelov E.V.
, Golovanov I.S.
, Ioffe S.L.
, Sukhorukov A.Y.
The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study
Molecules. 2020. V.25. N16. 3613 . DOI: 10.3390/molecules25163613 WOS Scopus OpenAlex
The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study
Molecules. 2020. V.25. N16. 3613 . DOI: 10.3390/molecules25163613 WOS Scopus OpenAlex
Идентификаторы БД:
| Web of science: | WOS:000577895700001 |
| Scopus: | 2-s2.0-85089408077 |
| OpenAlex: | W3048304762 |