- 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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p. 6752 - 6755
(2019/04/13)
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- Synthesis method and intermediate of ester derivative of (-)-cephalotaxine
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The invention discloses a synthesis method and an intermediate of an ester derivative of (-)-cephalotaxine. The synthesis method is characterized in that a compound A and a compound 4 undergoes a condensation reaction shown in the description in a solvent under the action of a condensing agent in order to obtain a compound I. The synthetic method utilizes an esterification reaction of a racemic epoxy branched-chain compound and the (-)-cephalotaxine to highly selectively obtain the chiral compound close to a single configuration, so the method has the advantages of simple and mild synthesis route, and easiness in industrialization.
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Paragraph 0216-0218
(2019/12/29)
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- METHODS AND INTERMEDIATES FOR THE PREPARATION OF OMACETAXINE AND CEPHALOTAXINE DERIVATIVES THEREOF
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The present invention relates to methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof. The resulting products are useful in the treatment of proliferative diseases and infectious diseases.
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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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- The first semi-synthesis of enantiopure homoharringtonine via anhydrohomoharringtonine from a preformed chiral acyl moiety
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(2'R,3S,4S,5R)-(-)-Homoharringtonine 2 was synthesized by direct esterification of cephalotaxine, using the activated forms of suitably substituted tetrahydropyrancarboxylic acids as sterically compact chiral side-chain precursors, followed by selective ring opening of the resulting (2'R,3S,4S,5R)-(-)-anhydrohomoharringtonine 6. Both enantiomers of the anhydro acyl moiety were prepared either by asymmetric α-hydroxyalkylation of the suitably substituted ethylenic α-ketoester 7 followed by acidic cyclisation, or by resolving the corresponding racemic mixture via formation of diastereomers with (-)quinine. Racemic cephalotaxine, as well as both its enantiomers, were prepared from natural - partially racemized - (-)- cephalotaxine 1.
- Robin, Jean-Pierre,Dhal, Robert,Dujardin, Gilles,Girodier, Laurent,Mevellec, Laurence,Poutot, Sandrine
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p. 2931 - 2934
(2007/10/03)
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- Studies in Cephalotaxus Alkaloids. Stereospecific Total Synthesis of Homoharringtonine
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The alkaloid ester homoharringtonine (2) was synthesized stereospecifically via the Reformatsky reaction of methyl α-bromoacetate with cephalotaxyl pyruvate (16) obtained by esterification of cephalotaxine with acid chloride derived from 15.The preparations of 2 and its unsaturated derivative 13 are described in detail.Possible explanations of the steric requirements in the esterification of cephalotaxine and of the steric outcome of the Reformatsky reaction leading to 2 and 13 are advanced.
- Hiranuma, Sayoko,Shibata, Misako,Hudlicky, Tomas
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p. 5321 - 5326
(2007/10/02)
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