An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases
| Autor: | M. Pilar Bosch, Angel Guerrero, Francisco Campos |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
biology
Trimethylsilyl Chemistry Stereochemistry Organic Chemistry Enantioselective synthesis Epoxide biology.organism_classification Catalysis Coupling reaction Inorganic Chemistry chemistry.chemical_compound biology.protein Amine gas treating Candida antarctica Physical and Theoretical Chemistry Lipase Triethylamine |
| Zdroj: | Tetrahedron: Asymmetry. 11:2705-2717 |
| ISSN: | 0957-4166 |
| DOI: | 10.1016/s0957-4166(00)00238-x |
| Popis: | The potent β 2 -adrenergic receptor agonist formoterol ( R,R )- 1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide ( R )- 6 with the unprotected primary amine ( R )- 9 . Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9 , we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of ( R )- 6 and ( R )- 9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol ( R , R )- 11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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