- Nucleoside drug 5' - position amino acid ester of the regioselective synthesis
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The invention relates to a regional selective synthesis method of a nucleoside drug 5'-site amino-acid ester having a structural characteristic as shown in a general formula I and a pharmaceutically acceptable salt thereof, wherein Base, R, R2 and R3 are defined in the specification. The method comprises the steps: utilizing triaryl methyl (Ar3C-) to selectively protect a nucleoside drug 5'-site hydroxy, then utilizing allyloxycarbonyl (AOC) to protect all the rest of active sites in a nucleoside drug base part and a sugar structure part, then selectively removing triaryl methyl under acidity, then carrying out condensation with a Boc-protected amino acid, selectively forming an ester at a 5' site of a nucleoside drug molecule, followed by carrying out palladium catalytic removal of AOC, and finally removing Boc under the acidic condition to form a corresponding salt. The method has high yield, allows the obtained product to be easy to separate and purify, and is more suitable for industrialized production.
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Paragraph 0036; 0037; 0038; 0039; 0040
(2017/07/04)
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- Regioselective synthesis of 5′-amino acid esters of some nucleosides via orthogonal protecting protocol
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Amino acid esters of nucleosides at 5′-position, as peptidomimetic prodrugs, which could be actively transported by the intestinal oligopeptide transporters 1 (PepT1), bear improved oral bioavailability. We established here a regioselective synthesis of the 5′-esters of some nucleosides via an orthogonal protecting protocol with triphenylmethyl (Tr) and allyloxycarbonyl (AOC) protecting groups. A series of 5′-esters of cytarabine and gemcitabine were selectively synthesized in over 36.0% total yields. This efficient and robust methodology will be examplified for the further study of the prodrugs of large number of antiviral and anticancer nucleosides.
- Liu, Jia-An,Guo, Xiao-Peng,Liang, Shuang,An, Fei,Shen, Hong-Yan,Xu, You-Jun
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supporting information
p. 1409 - 1412
(2015/02/19)
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