- The protecting-group free selective 3′-functionalization of nucleosides
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The direct and chemoselective 3′-phosphoramidation, phosphorylation and acylation of nucleosides are described. Upon the discovery of a novel 3′-phosphorylamidation of therapeutic nucleoside analogues with DBU, we explored the mechanism of this rare selectivity through a combination of NMR spectroscopy and computational studies. The NMR and computational findings allowed us to develop a predictive computational model that accurately assesses the potential for 3′-functionalization for a broad range of nucleosides and nucleoside mimetics. The synthetic utility of this model was exemplified by demonstration on a broad scope of nucleosides and electrophiles yielding targets that were previously only accessible via a protection/deprotection sequence or an enzymatic approach.
- McCabe Dunn, Jamie M.,Reibarkh, Mikhail,Sherer, Edward C.,Orr, Robert K.,Ruck, Rebecca T.,Simmons, Bryon,Bellomo, Ana
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- A high-purity rope fluorine cloth Wei compound and the preparation method of the substance
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The invention belongs to the technical field of medicine, and provides a method for preparing high-purity sofosbuvir, which comprises the following steps: carrying out deprotection on the accessible raw material SF-2 by using MeONa to generate a key intermediate SF-1, connecting with the side chain of phosphate, and treating to obtain the high-purity target product sofosbuvir, in which the impurity SF-P content is extremely low. The MeONa is creatively used as the deprotection reaction reagent, and the strongly-acidic resin is used for removing alkali in the after treatment, thereby simplifying the production technique and obtaining the intermediate key intermediate SF-1 with higher purity and yield. In the sofosbuvir preparation technique, the new after-treatment method is adopted to obtain the high-purity sofosbuvir API.
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Paragraph 0049-0053
(2017/08/25)
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- PROCESS FOR MAKING PHOSPHORUS-CONTAINING NUCLEOSIDE PRODRUG COMPOUNDS
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The present invention is directed to processes for making Compounds of Formula (IV): (IV) and salts thereof, wherein B, X, R1, R2, R3 and R4 are defined herein.
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Page/Page column 39; 41
(2017/02/24)
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