Halichondrin B: Synthesis of the C1−C22 Subunit
| Autor: | Steven D. Burke, Farid Benayoud, Gregory H Hanson, William T. Lambert |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Molecular Structure
Stereochemistry Organic Chemistry Acetal Molecular Conformation Enantioselective synthesis Stereoisomerism Nanotechnology Desymmetrization Chemical synthesis Tubulin Modulators Stereocenter Lactones chemistry.chemical_compound chemistry Ethers Cyclic Yield (chemistry) Michael reaction Macrolides Conduritol |
| Zdroj: | The Journal of Organic Chemistry. 70:9382-9398 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo051479m |
| Popis: | [Reaction: see text]. Two efficient routes to the C1-C22 subunit of halichondrin B are described. The cage ketal 7, which contains 11 asymmetric centers embedded within the ABCDEF-ring framework, was assembled from (+)-conduritol E (27) in 18 steps and 4% overall yield. In a separate route, 7 was also synthesized in 18 steps and 2% overall yield from a derivative of alpha-d-glucoheptonic acid gamma-lactone (62). While the former route installs the fully elaborated C-ring endowed with the correct C12 stereochemistry early in the synthesis, the latter features a late-stage introduction of the C12 stereocenter during the ultimate one-pot Michael addition/ketalization cascade to form the CDE-ring system of the cage. The importance of the C12 stereocenter to the crucial ketalization event is discussed through comparison of these two strategies. |
| Databáze: | OpenAIRE |
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