Cyclic 1,2-Diketones as Core Building Blocks: A Strategy for the Total Synthesis of (−)-Terpestacin
| Autor: | Guangbin Dong, Barry M. Trost, Jennifer A. Vance |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Alkylation
Stereochemistry Organic Chemistry Enantioselective synthesis Substituent Terpestacin Total synthesis Stereoisomerism General Chemistry Ketones Metathesis Article Catalysis Bridged Bicyclo Compounds Tsuji–Trost reaction chemistry.chemical_compound chemistry Michael reaction Chemoselectivity Oxidation-Reduction Palladium |
| Zdroj: | Chemistry - A European Journal. 16:6265-6277 |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | We report a full account of our work towards the total synthesis of (-)-terpestacin (1), a sesterterpene originally isolated from fungal strain Arthrinium sp. FA1744. Its promising anti-HIV and anti-cancer activity, as well as its novel structure, make terpestacin an attractive synthetic target. A strategy based on the unique reactivity of cyclic 1,2-diketones (diosphenols) was developed and total synthesis of 1 was achieved in 20 steps, in the longest linear sequence, from commercially available 2-hydroxy-3-methyl-2-cyclopenten-1-one. The key feature of our synthesis is the double usage of a "Pd AAA-Claisen" protocol (AAA=asymmetric allylic alkylation), first in the early stages to generate the C1 quaternary center and then in the late stages to install the side chain. In addition, a rather unusual ene-1,2-dione moiety was synthesized and utilized as an excellent Michael acceptor to attach the C15 substituent. Several possible routes towards the total synthesis have been examined and carefully evaluated. During our exploration many interesting chemoselectivity issues have been addressed, such as a highly selective ring-closing metathesis and a challenging oxidation of a disubstituted olefin in the presence of three trisubstituted ones. |
| Databáze: | OpenAIRE |
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