69152-87-0Relevant academic research and scientific papers
Design, Synthesis, and Activity Evaluation of Novel Acyclic Nucleosides as Potential Anticancer Agents in Vitro and in Vivo
Hao, Er-Jun,Li, Gong-Xin,Liang, Yu-Ru,Xie, Ming-Sheng,Wang, Dong-Chao,Jiang, Xiao-Han,Cheng, Jia-Yi,Shi, Zhi-Xian,Wang, Yang,Guo, Hai-Ming
supporting information, p. 2077 - 2109 (2021/02/16)
In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells in vitro, of which 3-(6-chloro-9H-purin-9-yl)dodecan-1-ol (9b) exhibited the most potent effect against the HCT-116 and SW480 cells with IC50 values of 0.89 and 1.15 μM, respectively. Furthermore, all of the (R)-configured acyclic nucleoside derivatives displayed more potent anticancer activity compared to their (S)-counterparts. Mechanistic studies revealed that compound 9b triggered apoptosis in the cancer cell lines via depolarization of the mitochondrial membrane and effectively inhibited colony formation. Importantly, compound 9b inhibited the growth of the SW480 xenograft in a mouse model with low systemic toxicity. These results indicated that acyclic nucleoside compounds are viable as potent and effective anticancer agents, and compound 9b may serve as a promising lead compound that merits further attention in future anticancer drug discovery.
Divergent Total Syntheses of (?)-Huperzine Q, (+)-Lycopladine B, (+)-Lycopladine C, and (?)-4-epi-Lycopladine D
Hong, Benke,Hu, Dachao,Wu, Jinbao,Zhang, Jing,Li, Houhua,Pan, Yingming,Lei, Xiaoguang
supporting information, p. 1557 - 1567 (2017/07/11)
We report herein our synthetic efforts towards the divergent syntheses of (?)-huperzine Q (1), (+)-lycopladine B (2), (+)-lycopladine C (3), and (?)-lycopladine D (4). The 10-step total synthesis of (?)-huperzine Q (1) and the first total syntheses of (+)
A TEMPO-free copper-catalyzed aerobic oxidation of alcohols
Xu, Boran,Lumb, Jean-Philip,Arndtsen, Bruce A.
supporting information, p. 4208 - 4211 (2015/04/14)
The copper-catalyzed aerobic oxidation of primary and secondary alcohols without an external N-oxide co-oxidant is described. The catalyst system is composed of a Cu/diamine complex inspired by the enzyme tyrosinase, along with dimethylaminopyridine (DMAP) or N-methylimidazole (NMI). The Cu catalyst system works without 2,2,6,6-tetramethyl-l-piperidinoxyl (TEMPO) at ambient pressure and temperature, and displays activity for un-activated secondary alcohols, which remain a challenging substrate for catalytic aerobic systems. Our work underscores the importance of finding alternative mechanistic pathways for alcohol oxidation, which complement Cu/TEMPO systems, and demonstrate, in this case, a preference for the oxidation of activated secondary over primary alcohols.
Chemo-, regio-, and stereo-selective perfluoroalkylations by a Grignard complex with zirconocene
Fujiu, Motohiro,Negishi, Kazuyuki,Guang, Jie,Williard, Paul G.,Kuroki, Shigeki,Mikami, Koichi
supporting information, p. 19464 - 19468 (2015/11/27)
The synthesis of highly reactive perfluoroalkyl Grignard reagents with early transition metal zirconocene complexes and their new types of highly chemo-, regio-, and stereo-selective perfluoroalkylation reactions are reported with epoxides in particular. The zirconocene complex is advantageous in activating the perfluoroalkyl Grignard species. The zirconocene·Grignard complexes were clarified by DOSY. Both 1H and 19F DOSY analyses show that the addition of MAO and dioxane to the mixture of RFMgCl and Cp2ZrCl2 connects Cp2Zr and RFMg to generate the zirconocene/perfluoroalkyl-Grignard/dioxane complex.
Oxidation of allylic and benzylic alcohols to aldehydes and carboxylic acids
K?nning, Daniel,Olbrisch, Tobias,Sypaseuth, Fanni D.,Tzschucke, C. Christoph,Christmann, Mathias
supporting information, p. 5014 - 5016 (2014/05/06)
An oxidation of allylic and benzylic alcohols to the corresponding carboxylic acids is effected by merging a Cu-catalyzed oxidation using O 2 as a terminal oxidant with a subsequent chlorite oxidation (Lindgren oxidation). The protocol was optimized to obtain pure products without chromatography or crystallization. Interception at the aldehyde stage allowed for Z/E-isomerization, thus rendering the oxidation stereoconvergent with respect to the configuration of the starting material.
Total synthesis of isoquinocyclinone
Dischmann, Mike,Frassetto, Timo,Breuning, M. André,Koert, Ulrich
supporting information, p. 11300 - 11302 (2014/10/15)
The total synthesis of the heptacyclic natural product isoquinocyclinone has been achieved. A Hauser annulation was used to assemble the anthraquinone core structure. The unique 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole substructure was prepared by alkyne addition to a lactone intermediate and subsequent Ni 0-mediated cyanide addition, the conversion of an O,O- into an N,O-acetal, and final intramolecular N-alkylation. Hauser annulation: An efficient total synthesis of isoquinocyclinone was achieved using a pentacyclic lactone as the key intermediate (see scheme). The pyrrolo-pyrrole substructure was elaborated by acetylide acylation, conversion of an O,O-acetal into an N,O-acetal, and intramolecular amidine alkylation.
Enantioselective synthesis of 3,4-dihydro-1,2-oxazepin-5(2 H)-ones and 2,3-dihydropyridin-4(1 H)-ones from β-substituted β- hydroxyaminoaldehydes
Ranade, Adwait R.,Georg, Gunda I.
, p. 984 - 992 (2014/03/21)
The synthesis of 3,4-dihydro-1,2-oxazepin-5(2H)-ones and 2,3-dihydropyridin-4(1H)-ones from β-substituted β- hydroxyaminoaldehydes is reported. The β-hydroxyaminoaldehydes were prepared by enantioselective organocatalytic 1,4-addition of N-tert-butyl (tert-butyldimethylsilyl)oxycarbamate to α,β-unsaturated aldehydes (MacMillan protocol). Alkyne addition to the aldehydes followed by alcohol oxidation furnished N-Boc O-TBS-protected β-aminoynones. Removal of the TBS protecting group initiated a 7-endo-dig cyclization to yield previously unknown 3,4-dihydro-1,2-oxazepin-5(2H)-ones. Reductive cleavage of the N-O bond of the oxazepinones and Boc-deprotection provided 2-substituted 2,3-dihydropyridin- 4(1H)-ones via 6-endo-trig cyclization. 2,3-Dihydropyridin-4(1H)-ones are versatile intermediates that have been used for the synthesis of many alkaloids. The new protocol allows the synthesis of 3-dihydropyridin-4(1H)-ones carrying an array of substituents at C2 that cannot be prepared from commercial β-amino acids or by one-carbon homologation of proteinogenic amino acids. The use of readily available β-hydroxylaminoaldehydes expands the utility of our previously reported method to prepare 2,3-dihydropyridin-4(1H)-ones from β-amino acids as the source of diversity and chirality. A broad substrate scope is possible because β-aminoaldehydes can be prepared from α,β-unsaturated aldehydes by an enantioselective organocatalytic process.
One-pot oxidation/isomerization of Z-allylic alcohols with oxygen as stoichiometric oxidant
Koenning, Daniel,Hiller, Wolf,Christmann, Mathias
supporting information, p. 5258 - 5261 (2013/01/15)
A method for generating (E)-α,β-unsaturated aldehydes from Z-allylic alcohols or E/Z-mixtures is described. The one-pot procedure involves a Cu-catalyzed oxidation followed by an organocatalytic Z/E-isomerization with N,N-dimethylaminopyridine (DMAP).
Dihydroxylation-based approach for the asymmetric syntheses of hydroxy-γ-butyrolactones
Peed, Jennifer,Davies, Iwan R.,Peacock, Lucy R.,Taylor, James E.,Kociok-Koehn, Gabriele,Bull, Steven D.
, p. 543 - 555 (2012/02/04)
A method of preparing enantiopure hydroxy-γ-butyrolactones containing multiple contiguous stereocenters in high yield with good diastereoselectivity has been developed. Osmium tetroxide mediated dihydroxylation of a range of β-alkenyl-β-hydroxy-N-acyloxazolidin-2-ones results in formation of triols that undergo spontaneous intramolecular 5-exo-trig cyclization reactions to provide hydroxy-γ-butyrolactones. The stereochemistry of these hydroxy-γ-butyrolactones has been established using NOE spectroscopy, which revealed that 1-substituted, 1,1-disubstituted, (E)-1,2-disubstituted, (Z)-1,2-disubstituted, and 1,1,2-trisubstituted alkenes undergo dihydroxylation with anti-diastereoselectivity, while 1,2,2-trisubstituted systems afford syn-diastereoisomers. The synthetic utility of this methodology has been demonstrated for the asymmetric synthesis of the natural product 2-deoxy-d-ribonolactone. Published 2011 by the American Chemical Society.
The stereochemical course and mechanism of the IspH reaction
Citron, Christian A.,Brock, Nelson L.,Rabe, Patrick,Dickschat, Jeroen S.
supporting information; experimental part, p. 4053 - 4057 (2012/06/01)
On the right path: The stereochemcial course of the IspH reaction, the last reaction in the deoxyxylulose phosphate pathway to terpenes, was investigated in feeding experiments with deuterated isotopologues of 1-deoxy-D-xylulose. The results support an enzyme mechanism for IspH that involves a previously suggested metallacyclopropane intermediate. Copyright
