- Gold(I)-Catalyzed Cyclization-3-Aza-Cope-Mannich Cascade and Its Application to the Synthesis of Cephalotaxine
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The discovery of a new gold(I)-catalyzed cascade reaction involving cyclization onto a vinylammonium, 3-aza-Cope rearrangement, and Mannich cyclization is reported. A variety of fused nitrogen heterocycles were prepared from simple cyclic tertiary amines using 1-5 mol % of a AuCl(PPh3)/Ag[C5(CN)5] cocatalyst system. The developed reaction was used in a study aimed at synthesizing cephalotaxine. A five-step operation from norhydrastinine provided demethylcephalotaxinone in 39.1% overall yield, which was transformed to (-)-cephalotaxine in two steps.
- Sakai, Takeo,Okumura, Chise,Futamura, Masatoshi,Noda, Naotaka,Nagae, Akari,Kitamoto, Chiharu,Kamiya, Madoka,Mori, Yuji
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p. 4391 - 4395
(2021/05/26)
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- ANALOGUES AND DERIVATIVES OF CEPHALOTAXINE AND METHODS FOR MAKING AND USING THE COMPOUNDS
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Disclosed herein are embodiments of a compound having a Formula I, or a salt, solvate, N-oxide, prodrug, diastereomer or enantiomer thereof. Also disclosed are derivative compounds made from the compound of Formula I. Certain derivative compounds have a Formula V-2, or a salt, solvate, N-oxide, prodrug, diastereomer or enantiomer thereoAlso disclosed are method for making and using the disclosed compounds. Certain disclosed embodiments are useful for treating and/or preventing certain diseases and/or disorders, including proliferation diseases, such as leukemia.
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- Total Synthesis of (?)-Cephalotaxine and (?)-Homoharringtonine via Furan Oxidation–Transannular Mannich Cyclization
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Homoharringtonine and its congener cephalotaxine were synthesized. Oxidative ring-opening of a furan unveils an amine-tethered dicarbonyl, which undergoes spontaneous transannular Mannich cyclization. The cascade builds the full cephalotaxine substructure in a single operation in 60 % yield. A Noyori reduction enabled synthesis of the title compounds with excellent enantioselectivity (krel=278).
- Ju, Xuan,Beaudry, Christopher M.
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supporting information
p. 6752 - 6755
(2019/04/13)
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- Stereoselectivity in N-Iminium Ion Cyclization: Development of an Efficient Synthesis of (±)-Cephalotaxine
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A stereoselective N-iminium ion cyclization with allylsilane to construct vicinal quaternary-tertiary carbon centers was developed for the concise synthesis of (±)-cephalotaxine. The current strategy features a TiCl4-promoted cyclization and ring-closure metathesis to furnish the spiro-ring system. The stereochemical outcome in the N-acyliminium ion cyclization was rationalized by the stereoelectronic effect of the Z- or E-allylsilane. Two diastereomers arising from the cyclization were merged into the formal synthesis of (±)-cephalotaxine.
- Liu, Hao,Yu, Jing,Li, Xinyu,Yan, Rui,Xiao, Ji-Chang,Hong, Ran
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supporting information
p. 4444 - 4447
(2015/09/28)
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- CEPHALOTAXUS ESTERS, METHODS OF SYNTHESIS, AND USES THEREOF
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The present invention provides novel cephalotaxus esters, syntheses thereof, and intermediates thereto. The invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of using said compounds or compositions in the treatment of proliferative diseases (e.g., benign neoplasm, cancer, inflammatory disease, autoimmune disease, diabetic retinopathy) and infectious disease. The invention further provides methods of using said compounds or compositions in the treatment of multidrug resistant cancer.
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Page/Page column 134
(2009/12/28)
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- Synthesis of antiproliferative cephalotaxus esters and their evaluation against several human hematopoietic and solid tumor cell lines: Uncovering differential susceptibilities to multidrug resistance
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Deoxyharringtonine (2), homoharringtonine (3), homodeoxyharringtonine (4), and anhydroharringtonine (5) are reported to be among the most potent members of the antileukemia alkaloids isolated from the Cephalotaxus genus. Convergent syntheses of these four natural products are described, each involving novel synthetic methods and strategies. These syntheses enabled evaluation of several advanced natural and non-natural compounds against an array of human hematopoietic and solid tumor cells. Potent cytotoxicity was observed in several cell lines previously not challenged with these alkaloids. Variations in the structure of the ester chain within this family of alkaloids confer differing activity profiles against vincristine-resistant HL-60/RV+, signalling new avenues for molecular design of these natural products to combat multi-drug resistance.
- Eckelbarger, Joseph D.,Wilmot, Jeremy T.,Epperson, Matthew T.,Thakur, Chandar S.,Shum, David,Antczak, Christophe,Tarassishin, Leonid,Djaballah, Hakim,Gin, David Y.
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supporting information; experimental part
p. 4293 - 4306
(2009/05/07)
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- Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the anti-leukemia alkaloid (-)-deoxyharringtonine
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Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is reported, involving novel synthetic methods and strategies that include (1) the strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro-pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core by α-(β-lactone)carboxylic acid derivatives to access the biologically active cephalotaxus esters. These innovations should allow rapid access not only to other Cephalotaxus alkaloids but also to non-natural analogues of potential therapeutic utility. Copyright
- Eckelbarger, Joseph D.,Wilmot, Jeremy T.,Gin, David Y.
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p. 10370 - 10371
(2007/10/03)
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- Total Synthesis of (-)-Cephalotaxine
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Total synthesis of (-)-cephalotaxine was achieved from D-(+)-proline by a short sequence of steps.The key intermediate, 1-azaspirononane, was prepared from vinyl iodide, using stannyl anion generated from Me3SiSnBu3 and CsF, in good yield.
- Isono, Naohiro,Mori, Miwako
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p. 115 - 119
(2007/10/02)
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- Total synthesis of the Cephalotaxus alkaloids dl-cephalotaxine, dl-11-hydroxycephalotaxine, and dl-drupacine
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This paper reports the chemical details of our total synthesis of dl-cephalotaxine (1) and the completion of the first total synthesis of dl-11-hydroxycephalotaxine (3) and dl-drupacine (4). Key steps in the synthesis of dl-cephalotaxine include: (1) conj
- Burkholder,Fuchs
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p. 9601 - 9613
(2007/10/02)
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- Biosynthesis of the Cephalotaxus Alkaloids. Investigations of the Early and Late Stages of Cephalotaxine Biosynthesis
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The biosynthesis of the alkaloid cephalotaxine (1) has been investigated by means of precursor incorporation experiments with Cephalotaxus harringtonia.It has been established that cephalotaxine is biosynthesized from one molecule each of tyrosine and phenylalanine in a manner consistent with the hypothesis that 1 is a modified 1-phenethyltetrahydroisoquinoline alkaloid.Incorporation experiments with - and phenylalanine have shown that one of the meta carbon atoms of phenylalanine is lost during the conversion of this amino acid into cephalotaxine.The remaining meta carbon atom is located at C-2 of the alkaloid.Cephalotaxine (1), cephalotaxinone (2), demethylcephalotaxinone (3), and demethylcephalotaxine (4) labeled with carbon-14 at C-3 have been synthesized.Incorporation experiments with these labeled alkaloids have established that cephalotaxine and cephalotaxinone are irreversibly demethylated in vivo.
- Parry, Ronald J.,Chang, Michael N. T.,Schwab, John M.,Foxman, B. M.
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p. 1099 - 1111
(2007/10/02)
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