- 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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- 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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