Microcosamine A, Microgrewiapine A and Microgrewiapine B: three homochiral alkaloids?
| Autor: | Ai M. Fletcher, Cameron E. Taylor, Stephen G. Davies, James E. Thomson, Paul M. Roberts |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
010405 organic chemistry
Stereochemistry Chemistry Organic Chemistry Enantioselective synthesis Absolute configuration 010402 general chemistry 01 natural sciences Biochemistry Reductive amination 0104 chemical sciences Stereocenter chemistry.chemical_compound Amide Drug Discovery Proton NMR Specific rotation Piperidine |
| Zdroj: | Tetrahedron. 89:132056 |
| ISSN: | 0040-4020 |
| Popis: | An asymmetric synthesis of microcosamine A, microgrewiapine A and microgrewiapine B (Microcos paniculata alkaloids) is reported. Conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl crotonate followed by enolate oxidation generates the C(2) and C(3) stereogenic centres of the targets, with subsequent diastereoselective intramolecular reductive amination being used to form the piperidine ring, simultaneously producing the C(6) stereogenic centre. 1H NMR 3J coupling constant and nOe analyses allow unambiguous assignment of relative configuration of the alkaloids. Comparison of specific rotation data for microcosamine A and microgrewiapine B is consistent with both possessing the absolute (2S,3R,6S)-configuration. For microgrewiapine A, conflicting data regarding the absolute configuration are revealed: in the isolation study a Mosher’s analysis concludes a (2S,3R,6S)-configuration, but comparison of specific rotation data suggests a (2R,3S,6R)-configuration. Thus it is promulgated it is imprudent to suggest the absolute configuration of this natural product; its re-isolation is required for resolution of this problem. |
| Databáze: | OpenAIRE |
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