115509-13-2Relevant articles and documents
Asymmetric Synthesis of (-)-6′-β-Fluoro-aristeromycin via Stereoselective Electrophilic Fluorination
Kim, Gyudong,Yoon, Ji-Seong,Jarhad, Dnyandev B.,Shin, Young Sup,Majik, Mahesh S.,Mulamoottil, Varughese A.,Hou, Xiyan,Qu, Shuhao,Park, Jiyong,Baik, Mu-Hyun,Jeong, Lak Shin
, p. 5732 - 5735 (2017)
(-)-6′-β-Fluoro-aristeromycin (2), a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, has been synthesized via stereoselective electrophilic fluorination followed by a purine base build-up approach. Interestingly, purine base condensation using a cyclic sulfate resulted in a synthesis of (+)-5′-β-fluoro-isoaristeromycin (2a). Computational analysis indicates that the fluorine atom controlled the regioselectivity of the purine base substitution.
Identification of a cytotoxic molecule in heat-modified citrus pectin
Leclere, Lionel,Fransolet, Maude,Cambier, Pierre,El Bkassiny, Sandy,Tikad, Abdellatif,Dieu, Marc,Vincent, Stéphane P.,Van Cutsem, Pierre,Michiels, Carine
, p. 39 - 51 (2016)
Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat-treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin.
From Carbohydrates to Carbocycles: Radical Routes via Tellurium Derivatives
Barton, Derek H. R.,Camara, Jose,Cheng, Xiaoqin,Gero, Stephane D.,Jaszberenyi, Joseph Cs.,Quiclet-Sire, Beatrice
, p. 9261 - 9276 (1992)
D-Ribose was transformed to its protected tosylate 15, followed by a Wittig-reaction to give 16 as a 3:1 mixture of the corresponding Z and E isomers.This mixture was then transformed to the anisyltelluride 17 and the latter cyclized in a radical exchange reaction to a mixture of the carbocycles 18a and 18b (in a 17:2 ratio).The major product 18a was then transformed to various chiral cyclopentane derivatives including the cyclopentenone-derivative 23.Various other carbohydrate-based approaches have also been explored.
Identification of 6′-β-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication
Chang, Tong-Shin,Hyun, Young Eum,Jang, Min Hwan,Jarhad, Dnyandev B.,Jeong, Lak Shin,Kim, Gyudong,Kim, Hong-Rae,Kovacikova, Kristina,Shin, Young Sup,Tipnis, Amol S.,Yoon, Ji-seong,van Hemert, Martijn J.
, (2020)
We have reported on aristeromycin (1) and 6′-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5′-phosphorylation, we designed and synthesized one-carbon homologated 6′-fluorinated-aristeromycin analogues. This modification prevents 5′-phosphorlyation by cellular kinases, whereas the inhibitory activity towards S-adenosyl-L-homocysteine (SAH) hydrolase will be retained. The enantiomerically pure 6′-fluorinated-5′-homoaristeromycin analogues 3a-e were synthesized via the electrophilic fluorination of the silyl enol ether with Selectfluor, using a base-build up approach as the key steps. All synthesized compounds exhibited potent inhibitory activity towards SAH hydrolase, among which 6′-β-fluoroadenosine analogue 3a was the most potent (IC50 = 0.36 μM). Among the compounds tested, 6′-β-fluoro-homoaristeromycin 3a showed potent antiviral activity (EC50 = 0.12 μM) against the CHIKV, without noticeable cytotoxicity up to 250 μM. Only 3a displayed anti-CHIKV activity, whereas both3a and 3b inhibited SAH hydrolase with similar IC50 values (0.36 and 0.37 μM, respectively), which suggested that 3a's antiviral activity did not merely depend on the inhibition of SAH hydrolase. This is further supported by the fact that the antiviral effect was specific for CHIKV and some other alphaviruses and none of the homologated analogues inhibited other RNA viruses, such as SARS-CoV, MERS-CoV, and ZIKV. The potent inhibition and high selectivity index make 6′-β-fluoro-homoaristeromycin (3a) a promising new template for the development of antivirals against CHIKV, a serious re-emerging pathogen that has infected millions of people over the past 15 years.
Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development
Shaw, Scott A.,Balasubramanian, Balu,Bonacorsi, Samuel,Cortes, Janet Caceres,Cao, Kevin,Chen, Bang-Chi,Dai, Jun,Decicco, Carl,Goswami, Animesh,Guo, Zhiwei,Hanson, Ronald,Humphreys, W. Griffith,Lam, Patrick Y. S.,Li, Wenying,Mathur, Arvind,Maxwell, Brad D.,Michaudel, Quentin,Peng, Li,Pudzianowski, Andrew,Qiu, Feng,Su, Shun,Sun, Dawn,Tymiak, Adrienne A.,Vokits, Benjamin P.,Wang, Bei,Wexler, Ruth,Wu, Dauh-Rurng,Zhang, Yingru,Zhao, Rulin,Baran, Phil S.
, p. 7019 - 7032 (2015/07/27)
Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed. (Chemical Equation Presented).
