A Formal Total Synthesis of (-)-Cephalotaxine
| Autor: | Serry A. A. El Bialy, Said M. Bayomi, Tatsunori Sato, Ken-ichi Hirose, Miho Kotake, Takayuki Yakura, Ali M. Abdelal, Masazumi Ikeda, Ihsan A. Shehata, Laila M. Gad |
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| Rok vydání: | 1999 |
| Předmět: |
Diketone
chemistry.chemical_classification Harringtonines Ketone Total synthesis Acetylation Borohydrides General Chemistry General Medicine Antineoplastic Agents Phytogenic Chemical synthesis Catalysis Sodium borohydride chemistry.chemical_compound chemistry Drug Discovery Organic chemistry Indicators and Reagents Aldol condensation Homoharringtonine Enantiomeric excess Derivative (chemistry) |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 47:983-987 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.47.983 |
| Popis: | A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound. |
| Databáze: | OpenAIRE |
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