865363-93-5Relevant articles and documents
Nine-Step Stereoselective Synthesis of Islatravir from Deoxyribose
Nawrat, Christopher C.,Whittaker, Aaron M.,Huffman, Mark A.,McLaughlin, Mark,Cohen, Ryan D.,Andreani, Teresa,Ding, Bangwei,Li, Hongming,Weisel, Mark,Tschaen, David M.
, p. 2167 - 2172 (2020)
A stereoselective nine-step synthesis of the potent HIV nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir (EfdA, MK-8591) from 2-deoxyribose is described. Key findings include a diastereodivergent addition of an acetylide nucleophile to an enolizable ketone, a chemoselective ozonolysis of a terminal olefin and a biocatalytic glycosylation cascade that uses a unique strategy of byproduct precipitation to drive an otherwise-reversible transformation forward.
Enantioselective Synthesis of 4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) via Enzymatic Desymmetrization
McLaughlin, Mark,Kong, Jongrock,Belyk, Kevin M.,Chen, Billy,Gibson, Andrew W.,Keen, Stephen P.,Lieberman, David R.,Milczek, Erika M.,Moore, Jeffrey C.,Murray, David,Peng, Feng,Qi, Ji,Reamer, Robert A.,Song, Zhiguo J.,Tan, Lushi,Wang, Lin,Williams, Michael J.
, p. 926 - 929 (2017)
An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features of stereocontrol include construction of the fully substituted 4′-carbon via a biocatalytic desymmetrization of 2-hydroxy-2-((triisopropylsilyl)ethynyl)propane-1,3-diyl diacetate and a Noyori-type asymmetric transfer hydrogenation to control the stereochemistry of the 3′-hydroxyl bearing carbon. The discovery of a selective crystallization of an N-silyl nucleoside intermediate enabled isolation of the desired β-anomer from the glycosylation step.
Synthesis of nucleotide analogues, EFdA, EdA and EdAP, and the effect of EdAP on hepatitis B virus replication
Kamata, Mai,Takeuchi, Toshifumi,Hayashi, Ei,Nishioka, Kazane,Oshima, Mizuki,Iwamoto, Masashi,Nishiuchi, Kota,Kamo, Shogo,Tomoshige, Shusuke,Watashi, Koichi,Kamisuki, Shinji,Ohrui, Hiroshi,Sugawara, Fumio,Kuramochi, Kouji
, p. 217 - 227 (2020)
4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) and 4′-ethynyl-2′-deoxyadenosine (EdA) are nucleoside analogues which inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. EdAP, a cyclosaligenyl (cycloSal) phosphate derivative of EdA, inhibits the replication of the influenza A virus. The common structural feature of these compounds is the ethynyl group at the 4′-position. In this study, these nucleoside analogues were prepared by a common synthetic strategy starting from the known 1,2-di-O-acetyl-D-ribofuranose. Biological evaluation of EdAP revealed that this compound reduced hepatitis B virus (HBV) replication dose-dependently without cytotoxicity against host cells tested in this study.
ENGINEERED PURINE NUCLEOSIDE PHOSPHORYLASE VARIANT ENZYMES
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Paragraph 0192-0194; 0200-0208, (2020/02/06)
The present invention provides engineered purine nucleoside phosphorylase (PNP) enzymes, polypeptides having PNP activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing PNP enzymes are also provided. The present invention further provides compositions comprising the PNP enzymes and methods of using the engineered PNP enzymes. The present invention finds particular use in the production of pharmaceutical compounds.