51600-11-4Relevant academic research and scientific papers
Discovery of Leucyladenylate Sulfamates as Novel Leucyl-tRNA Synthetase (LRS)-Targeted Mammalian Target of Rapamycin Complex 1 (mTORC1) Inhibitors
Yoon, Suyoung,Kim, Jong Hyun,Kim, Sung-Eun,Kim, Changhoon,Tran, Phuong-Thao,Ann, Jihyae,Koh, Yura,Jang, Jayun,Kim, Sungmin,Moon, Hee-Sun,Kim, Won Kyung,Lee, Sangkook,Lee, Jiyoun,Kim, Sunghoon,Lee, Jeewoo
, p. 10322 - 10328 (2016/12/07)
Recent studies indicate that LRS may act as a leucine sensor for the mTORC1 pathway, potentially providing an alternative strategy to overcome rapamycin resistance in cancer treatments. In this study, we developed leucyladenylate sulfamate derivatives as LRS-targeted mTORC1 inhibitors. Compound 18 selectively inhibited LRS-mediated mTORC1 activation and exerted specific cytotoxicity against colon cancer cells with a hyperactive mTORC1, suggesting that 18 may offer a novel treatment option for human colorectal cancer.
Direct One-Pot Synthesis of Nucleosides from Unprotected or 5-O-Monoprotected d -Ribose
Downey, A. Michael,Richter, Celin,Pohl, Radek,Mahrwald, Rainer,Hocek, Michal
supporting information, p. 4604 - 4607 (2015/09/28)
New, improved methods to access nucleosides are of general interest not only to organic chemists but to the greater scientific community as a whole due their key implications in life and disease. Current synthetic methods involve multistep procedures employing protected sugars in the glycosylation of nucleobases. Using modified Mitsunobu conditions, we report on the first direct glycosylation of purine and pyrimidine nucleobases with unprotected d-ribose to provide β-pyranosyl nucleosides and a one-pot strategy to yield β-furanosides from the heterocycle and 5-O-monoprotected d-ribose.
Synthesis and stability of a 2′-O-[N-(aminoethyl)carbamoyl] methyladenosine-containing dinucleotide
Milton, Stefan,Ander, Charlotte,Honcharenko, Dmytro,Honcharenko, Malgorzata,Yeheskiely, Esther,Stroemberg, Roger
supporting information, p. 7184 - 7192 (2013/11/06)
Working towards the synthesis of 2′-O-[N-(aminoethyl)carbamoyl] methyl-modified di- and oligonucleotides, we have synthesised a protected 2′-O-[N-(aminoethyl)carbamoyl]methyl-modified adenosine where the modification is introduced in a convenient one-pot three-step procedure. The corresponding H-phosphonate building block was also synthesised, and from this intermediate, a 2′-O-[N-(aminoethyl)carbamoyl]methyl-containing dinucleotide could be made. We also performed studies on the chemical and enzymatic stability of this dinucleotide. The dinucleotide was subjected to different ammonolysis and other basic conditions, and HPLC analysis showed that the modification was intact to most conditions, but that there was some minor hydrolysis when NH3 (concd. aq.) was used at 55 °C. Under several other sets of conditions, including saturated NH3 in methanol, and ethylenediamine, the amide remained intact. Treatment of the dinucleotide with Phosphodiesterase I from Crotalus adamanteus venom and Phosphodiesterase II from bovine spleen showed that the N-(aminoethyl)carbamoylmethyl moiety gives the phosphodiester linkage substantial protection against enzymatic degradation; the phosphodiester was not degraded by PDE II at all after seven days. A 2′-O-[N-(aminoethyl)carbamoyl]methyl-modified adenosine and a corresponding dinucleotide were synthesised. Hydrolysis (1-2 %) was observed in concentrated aqueous NH3 at 55°C, but under several other sets of reaction conditions, the amide remained intact. The N-(aminoethyl) carbamoylmethyl moiety gave substantial protection against enzymatic degradation by nucleases from snake venom and bovine spleen. Copyright
Nucleosides. Part LI. The 2-(4-Nitrophenyl)ethoxycarbonyl (npeoc) and 2-(2,4-Dinitrophenyl)ethoxycarbonyl (dnpeoc) Groups for Protection of Hydroxy Functions in Ribonucleosides and 2'-Deoxyribonucleosides
Schirmeister, Helga,Himmelsbach, Frank,Pfleiderer, Wolfgang
, p. 385 - 401 (2007/10/02)
The common 2'-deoxypyrimidine and -purine nucleosides, thymidine (4), O4-thymidine (17), 2'-deoxy-N4-cytidine (26), 2'-deoxy-N6-adenosine (39), and 2'-deoxy-N2--O6-guanosine (52) were further protected by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and the 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) group at the OH functions of the sugar moiety to form new partially and fully blocked intermediates for nucleoside and nucleotide syntheses.The corresponding 5'-O-monomethoxytrityl derivatives 5, 18, 30, 40, and 56 were also used as starting material to synthesize some other intermediates which were not obtained by direct acylations.In the ribonucleoside series, the 5'-O-monomethoxytrityl derivatives 14, 36, 49, and 63 reacted with 2-(4-nitrophenyl)ethyl chloroformate (1) to the corresponding 2',3'-bis-carbonates 15, 37, 50, and 64 which were either detritylated to 16, 38, 51, and 65, respectively, or converted by 1,8-diazabicycloundec-7-ene (DBU) treatment to the 2',3'-cyclic carbonates 66-69.The newly synthesized compounds were characterized by elemental analyses and UV and 1H-NMR spectra.
Synthesis and Conformation of 9-(3'-C-Methyl-β-D-xylo-furanosyl)adenin and 3-C'-Methyladenosine, Two Sugar-Methylated Nucleoside Analogues
Koole, Leo H.,Buck, Henk M.,Vial, Jean-Marc,Chattopadhyaya, Jyoti
, p. 665 - 669 (2007/10/02)
A novel synthetic route for the sugar-methylated nucleoside analogue 9-(3-C'-methyl-β-D-xylo-furanosyl)adenine (1) is reported.A Grignard reaction in THF with an appropriately protected keto nucleoside gave the xylo structure 4 in 60percent yield.Using diethyl ether as the solvent, the Grignard reaction furnished compound 4 in 35percent yield, along with the ribo epimer (ca. 1percent).The ribo epimer is the precursor of 3'-C-methyladenosine (2).Compounds 4 and 5 could be conveniently deprotected to obtain the title compounds in good yields.The conformational properties of 1 and 2 were analyzed using 500 MHz 1H NMR spectroscopy.In line with earlier experiments, it is found that the methyl group on the sugar ring strongly prefers an equatorial location.For 1, this results in the predominant population of the North (3T2) puckered form of the sugar ring, whereas compound 2 resides primarily in the South (2T3) conformation.
REACTION OF ADENINE NUCLEOSIDES, TOSYLATED IN THE CARBOHYDRATE MOIETY, WITH LITHIUM TRIETHYLBOROHYDRIDE
Herdewijn, Piet
, p. 6563 - 6580 (2007/10/02)
The reaction of lithium triethylborohydride with the 2',3'-di-O-p-tolylsulphonyl derivatives of 9-β-D-ribofuranosyladenine, 9-β-D-arabinofuranosyladenine, 9-β-D-xylofuranosyladenine and 9-β-D-lyxofuranosyladenine was studied.The reaction of 2',3'-di-O-p-tolylsulphonyladenosine with LiEt3BH gave 9-(3-deoxy-β-D-threo-pentofuranosyl)adenine.This rearrangement reaction was used for the synthesis of 9-(3,5-dideoxy-β-D-threo-pentofuranosyl)adenine in one step from 2',3',5'-tri-O-p-tolylsulphonyladenosine in 58percent yield.The p-tolylsulphonyl group in the 2'-"up" configuration of unprotected adenine nucleosides was preferentially attacked by LiEt3BH giving S-O-bond scission.This was shown by the formation of 9-(3-deoxy-β-D-threo-pentofuranosyl)adenine from 2',3'-di-O-p-tolylsulphonyl-9-β-D-arabinofuranosyladenine and by the formation of 9-β-D-lyxofuranosyladenine from 2'-O-p-tolylsulphonyl-9-β-D-lyxofuranosyladenine with LiEt3BH. 9-β-D-Lyxofuranosyladenine was synthesized from 3',5'-di-O-benzoyl-9-β-D-xylofuranosyladenosine in 88percent yield using a triflate displacement reaction.
