AI Article Synopsis
- * A key part of this process involves creating a type of chemical structure called 1,2-oxazine, which was done using a combination of other chemicals.
- * Interesting calculations suggest that a change in the chemical structure (epimerization) happens through a unique and complex chemical formation involving several parts of the molecule working together.
Article Abstract
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--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 NaBHCN 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464803 | PMC |
| http://dx.doi.org/10.3390/molecules25163613 | DOI Listing |
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