19490-92-7Relevant articles and documents
An unusual ligand coordination gives rise to a new family of rhodium metalloinsertors with improved selectivity and potency
Komor, Alexis C.,Barton, Jacqueline K.
, p. 14160 - 14172 (2014)
Rhodium metalloinsertors are octahedral complexes that bind DNA mismatches with high affinity and specificity and exhibit unique cell-selective cytotoxicity, targeting mismatch repair (MMR)-deficient cells over MMR-proficient cells. Here we describe a new generation of metalloinsertors with enhanced biological potency and selectivity, in which the complexes show Rh-O coordination. In particular, it has been found that both δ- and -[Rh(chrysi)(phen)(DPE)]2+ (where chrysi =5,6 chrysenequinone diimmine, phen =1,10-phenanthroline, and DPE = 1,1-di(pyridine-2-yl)ethan-1-ol) bind to DNA containing a single CC mismatch with similar affinities and without racemization. This is in direct contrast with previous metalloinsertors and suggests a possible different binding disposition for these complexes in the mismatch site. We ascribe this difference to the higher pKa of the coordinated immine of the chrysi ligand in these complexes, so that the complexes must insert into the DNA helix with the inserting ligand in a buckled orientation; spectroscopic studies in the presence and absence of DNA along with the crystal structure of the complex without DNA support this assignment. Remarkably, all members of this new family of compounds have significantly increased potency in a range of cellular assays; indeed, all are more potent than cisplatin and N-methyl-N'-nitro-nitrosoguanidine (MNNG, a common DNA-alkylating chemotherapeutic agent). Moreover, the activities of the new metalloinsertors are coupled with high levels of selective cytotoxicity for MMR-deficient versus proficient colorectal cancer cells.
A Journey through Hemetsberger–Knittel, Leimgruber–Batcho and Bartoli Reactions: Access to Several Hydroxy 5- and 6-Azaindoles
Radix, Sylvie,Hallé, Fran?ois,Mahiout, Zahia,Teissonnière, Amélie,Bouchez, Grégoire,Auberger, Ludovic,Barret, Roland,Lomberget, Thierry
, (2022/02/22)
The preparation of various 5- and 6-azaindoles, heterocyclic structures that are frequently part of molecules in clinical development, and their monohydroxy analogues were described. Different strategies, relying on the de novo pyrrole ring formation, were investigated and, thanks to Hemetsberger–Knittel, Bartoli and Leimgruber–Batcho approaches, 4- and 7-monohydroxy 5- and 6-azaindoles were obtained. The crucial introduction of the oxygen atom was carried out from halogen derivatives, using nucleophilic substitution reactions under basic conditions with or without a copper catalyst. Some preliminary oxidation reactions have shown that it was yet not possible to synthesize the azaquinone indole structure from monohydroxy azaindole, using molecular oxygen in the presence of salcomine as a catalyst.
Mild Condition for the Deoxygenation of α-Heteroaryl-Substituted Methanol Derivatives
Meng, Na,Yu, Wensheng,Suzuki, Takao,Chen, Maofen,Qi, Zhiqi,Hu, Bin,Bao, Jianming,Debenham, John S.,Mazzola, Robert,Duffy, Joseph L.
, p. 5560 - 5567 (2021/05/04)
A mild condition via PPh3/I2/imidazole for the deoxygenation of substituted methanol derivatives has been identified. This metal-free process was found to proceed well on secondary or tertiary alcohols substituted with one or two heteroaryl groups, and it tolerates acid-sensitive heterocycles. This condition works for methanol derivatives substituted with 2-pyridyl, 4-pyridyl, or other heterocyclic groups, allowing the negative charge formed during the reaction to resonate to a nitrogen atom. Methanol derivatives substituted with 3-pyridyl or heterocyclic groups that do not allow the negative charge formed during the reaction to resonate to a nitrogen atom will not undergo deoxygenation under this condition.
Green synthesis method of polyaryl substituted methanol
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Paragraph 0127-0136, (2021/04/17)
The invention relates to a green synthesis method of polyaryl substituted methanol, in particular to a method for efficiently synthesizing polyaryl substituted methanol in a polar aprotic solvent under the condition of an oxidizing agent by taking polyaryl substituted methane as a raw material and alkali as an additive. The method provided by the invention is green and environment-friendly, avoids using expensive metal catalysts, and has the advantages of low cost, few reaction steps, short time, high yield and the like.
Transition-Metal Free Chemoselective Hydroxylation and Hydroxylation-Deuteration of Heterobenzylic Methylenes
Fu, Yiwei,Li, Hao,Liu, Yonghai,Mang, Zhiguo,Shi, Lei,Sun, Chengyu,Yu, Yang
supporting information, p. 8127 - 8131 (2020/11/03)
We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41-76% yields. Using DMSO-d6, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.
Difunctionalization of Alkenylpyridine N-Oxides by the Tandem Addition/Boekelheide Rearrangement
Xun, Xudong,Zhao, Man,Xue, Jianzhong,Hu, Tao,Zhang, Ming,Li, Guofeng,Hong, Liang
supporting information, p. 8266 - 8269 (2019/10/16)
A convenient and efficient approach for the difunctionalization of alkenylpyridine N-oxides through the tandem addition/Boekelheide rearrangement has been developed. The C-O and C-X (S, O, Cl) bonds are constructed simultaneously at the α- and β-positions under mild reaction conditions in 100% atom economy, which complements previously reported α- or β-functionalizations.
Iron-Catalyzed Aerobic Oxidation of (Alkyl)(aryl)azinylmethanes
Sterckx, Hans,Sambiagio, Carlo,Lemière, Filip,Tehrani, Kourosch Abbaspour,Maes, Bert U. W.
, p. 1564 - 1570 (2017/08/11)
An iron-catalyzed aerobic oxidation of (alkyl)(aryl)azinylmethanes has been developed leading to tertiary alcohols in moderate to good yields. Hock rearrangement was identified as a major side reaction leading to a complex mixture of undesired products. Addition of thiourea sometimes allows inhibiting this side reaction and steers the reaction towards the desired products.
β-Selective Reductive Coupling of Alkenylpyridines with Aldehydes and Imines via Synergistic Lewis Acid/Photoredox Catalysis
Lee, Katarzyna N.,Lei, Zhen,Ngai, Ming-Yu
supporting information, p. 5003 - 5006 (2017/05/04)
Umpolung (polarity reversal) strategies of aldehydes and imines have dramatically expanded the scope of carbonyl and iminyl chemistry by facilitating reactions with non-nucleophilic reagents. Herein, we report the first visible light photoredox-catalyzed β-selective reductive coupling of alkenylpyridines with carbonyl or iminyl derivatives with the aid of a Lewis acid co-catalyst. Our process tolerates complex molecular scaffolds (e.g., sugar, natural product, and peptide derivatives) and is applicable to the preparation of compounds containing a broad range of heterocyclic moieties. Mechanistic investigations indicate that the key step involves single-electron-transfer reduction of aldehydes or imines followed by the addition of resulting ketyl or α-aminoalkyl radicals to Lewis acid-activated alkenylpyridines.
A method for preparing many west pulls sensitively succinic acid
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Paragraph 0032-0034, (2017/03/08)
The invention relates to a preparation method of doxylamine succinate. The preparation method comprises the steps as follows: firstly, a Grignard reagent generated by iodobenzene and magnesium reacts with 2-acetylpyridine to generate 2-pyridyl phenyl methyl alcohol, the 2-pyridyl phenyl methyl alcohol is recrystallized to be purified, then the 2-pyridyl phenyl methyl alcohol reacts with sodium amide and 2-dimethylamino chloroethane sequentially, doxylamine is obtained and has a salt forming reaction with succinic acid finally, and the doxylamine succinate is obtained. The preparation method is high in reaction efficiency, lower in cost and applicable to industrial mass production.
PBr3-mediated unexpected reductive deoxygenation of α-aryl-pyridinemethanols: Synthesis of arylmethylpyridines
Nishigaya, Yosuke,Umei, Kentaro,Watanabe, Daisuke,Kohno, Yasushi,Seto, Shigeki
supporting information, p. 1566 - 1572 (2016/03/01)
PBr3-mediated reductive deoxygenation of α-aryl-pyridinemethanols to provide arylmethylpyridines is described, the alcohol substrate scope is explored, free radical trap TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) is introduced, and the hydrogen source of the methylene product is defined. The unexpected reaction enabled us to prepare previously inaccessible, novel EP1 antagonists.
