A Formal Total Synthesis of (-)-Cephalotaxine

A Formal Total Synthesis of (-)-Cephalotaxine

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 c...

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Bibliographic Details
Published in:Chemical & pharmaceutical bulletin Vol. 47; no. 7; pp. 983 - 987
Main Authors: IKEDA, Masaszumi, BIALY, Serry A.A. EL, HIROSE, Ken-ichi, KOTAKE, Miho, SATO, Tatsunori, BAYOMI, Said M.M., SHEHATA, Ihsan A., ABDELAL, Ali M., GAD, Laila M., YAKURA, Takayuki
Format: Journal Article
Language:English
Published: Tokyo The Pharmaceutical Society of Japan 01-07-1999
Maruzen
Japan Science and Technology Agency
Subjects:
(-)-cephalotaxine
Acetylation
Antineoplastic Agents, Phytogenic - chemical synthesis
Borohydrides
Catalysis
Chemistry
D-proline
Exact sciences and technology
Friedel-Crafts alkylation
Harringtonines - chemical synthesis
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Homoharringtonine
Indicators and Reagents
intramolecular aldol condensation
intramolecular Heck reaction
Organic chemistry
Preparations and properties
Pummerer reaction
Pentacyclic compound
Intramolecular reaction
Enantioselectivity
Pummerer reaction
Lactam
Proline
Aldol condensation
α-Aminoacid
Alkaloid
Friedel Crafts reaction
Asymmetric synthesis
Enantiomeric excess
Aromatic compound
Chemical synthesis
Oxygen nitrogen heterocycle
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Summary: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 benzone at room temperature gave the α, β-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 folowing the synthetic operations developed for the synthesis of the racemic compound.
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ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.47.983