Enantioselective synthesis of key intermediates in a novel approach towards the Iboga-alkaloid family
| Autor: | Hans-Jürg Borschberg, Stefan Höck |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
chemistry.chemical_classification
Iboga alkaloid Ketone Bicyclic molecule Stereochemistry Organic Chemistry Enantioselective synthesis Absolute configuration Diastereomer Ireland-Claisen Rearrangemenent Biochemistry Catalysis Cycloaddition Indole Alkaloids Enantioselektive Synthesis 540: Chemie Inorganic Chemistry chemistry Drug Discovery Physical and Theoretical Chemistry Enantiomer |
| Popis: | Significant improvements in the realm of a recently disclosed, novel synthetic concept towards the Iboga alkaloid family are presented. The key step for the construction of the bicyclic aliphatic core consists of an intramolecular nitrone-olefin 1,3‐dipolar cycloaddition reaction of a 1 : 1 mixture 15/16 yielding the two diastereoisomeric tricyclic isoxazolidine derivatives 17 and 18. The required nitrones were prepared from the readily available (S)‐hydroxylactone 6 in twelve steps with an overall yield of 15% (average: 83.5% per step). The relative configuration of the minor isomer was deduced unambiguously by single‐crystal X‐ray analysis of the derived tricyclic carbamate 21. As four out of five asymmetric centers in the pair 17/18 have opposite configuration, destruction of the one possessing the same absolute configuration transforms the original set of diastereoisomers into a pair of enantiomers. We verified this contention by oxidizing the two alcohols 20 and 22 to yield the two antipodal forms of ketone 23. The absence of significant amounts of by‐product and the high reproducibility of the crucial cycloaddition reaction represent marked improvements over our earlier attempts. In addition, the new route, which starts from L‐glutamate, should provide access to both naturally occurring antipodal series of the targeted alkaloid class. |
| Databáze: | OpenAIRE |
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