13709-05-2Relevant articles and documents
Enantioselective total synthesis of (+)-stephadiamine through bioinspired aza-benzilic acid type rearrangement
Odagi, Minami,Matoba, Taisei,Hosoya, Keisuke,Nagasawa, Kazuo
, p. 2699 - 2704 (2021)
We report the first enantioselective total syntheses of the hasubanan alkaloid (-)-metaphanine and the norhasubanan alkaloid (+)-stephadiamine. Key features of these syntheses include diastereoselective oxidative phenolic coupling reaction and subsequent
Design, synthesis, and evaluation of a water soluble C5-monoketone type curcumin analogue as a potent amyloid β aggregation inhibitor
Hotsumi, Mayumi,Tajiri, Misato,Nikaido, Yuri,Sato, Taki,Makabe, Koki,Konno, Hiroyuki
, p. 2157 - 2161 (2019)
A structure activity relationship study of curcumin analogues for the inhibition of amyloid β aggregation is described. Optimization of the o-phenol and olefin spacer resulted in the identification of the C5-monoketone type curcumin analogue AY1319, which
Structure-activity relationships of semisynthetic mumbaistatin analogs
Lee, Taek Soon,Das, Abhirup,Khosla, Chaitan
, p. 5207 - 5218 (2007)
Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent known inhibitors of hepatic glucose-6-phosphate translocase, an important target for the treatment of type II diabetes. Its availability, however, has been limited due to its extremely low yield from the natural source. Starting from DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related polyketide product of engineered biosynthesis, we developed a facile semisynthetic method that afforded a variety of mumbaistatin analogs within five steps. This work was facilitated by the initial development of a DMAC overproduction system. In addition to reinforcing the biological significance of the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were found to have low micromolar potency against the translocase in vitro. Two of them were also active in glucose release assays from primary hepatocytes. The synergistic combination of biosynthesis and synthesis is a promising avenue for the discovery of new bioactive substances.
2-(3-Hydroxybenzyl)benzo[d]isothiazol-3(2H)-one Mannich base derivatives as potential multifunctional anti-Alzheimer’s agents
He, Yuxi,Xiao, Ganyuan,Yu, Guangjun,Song, Qing,Zhang, Heng,Liu, Zhuoling,Tan, Zhenghuai,Deng, Yong
, p. 1249 - 1264 (2021/05/11)
A series of 2-(3-hydroxybenzyl)benzo[d]isothiazol-3(2H)-one Mannich base derivatives were designed as potential multifunctional agents against Alzheimer’s disease. The twelve derivatives were synthesized and evaluated with various biological activities. I
Tethered aryl groups increase the activity of anti-proliferative thieno[2,3-b]pyridines by targeting a lipophilic region in the active site of PI-PLC
Barker, David,Haverkate, Natalie A.,Leung, Euphemia,Pilkington, Lisa I.
, (2021/12/02)
The compounds 2-amino-3-carboxamido-thieno[2,3-b]pyridines have demonstrated excel-lent anti-proliferative activity against human cancer cell lines, including the triple-negative breast cancer cell line MDA-MB-231. In this study, 81 novel thieno[2,3-b]pyridines were synthesised in four series to further improve their anti-proliferative activity, in particular by targeting an adjacent lipophilic pocket in the putative target enzyme phosphoinositide phospholipase C (PI-PLC). Overall, it was found that appending a propyl-aryl group at C-5 on 2-amino-3-carboxamido-thieno[2,3-b]pyridine resulted in compounds with potent biological activity, exhibiting IC50 values in the nanomolar range. The propyl linker could be an α,β-unsaturated ketone or a saturated propyl ketone, but the highest activity was obtained when allylic alcohols were the tether between thieno[2,3-b]pyridine and the appended aryl group, with compound 21r having IC50 values lower than 50 nM. Compounds with one extra carbon in the tether (i.e., a four-atom chain) were found to be considerably less active. Molecular modelling revealed this propyl tether places the newly introduced aryl ring in an untargeted lipophilic pocket within the active site of the phosphoinositide phospholipase C (PI-PLC) enzyme.
TRPV3 inhibitor and preparation method thereof
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Paragraph 0064-0071; 0072; 0079; 0080; 0086; 0088; 0095, (2021/04/26)
The invention discloses a TRPV3 inhibitor which is formed by sequentially connecting an R1 group, an R group and an R2 group, and the molecular structural general formula of the TRPV3 inhibitor is shown as a formula 1 in the description. The invention als
Exploration of chiral diastereomeric spiroketal (SPIROL)-based phosphinite ligands in asymmetric hydrogenation of heterocycles
Sun, Siyuan,Nagorny, Pavel
supporting information, p. 8432 - 8435 (2020/08/13)
New and readily available chiral SPIROL-based diphosphinite ligands (SPIRAPO) have been prepared and employed for iridium-catalyzed asymmetric hydrogenations of quinolines, quinoxalines and 2H-1,4-bezoxazin-2-ones. While the structurally similar (R,R,R)-SPIRAPO and (R)-SPINOL-based phosphinites were not the best ligands for these transformations, the (S,R,R)-diastereomer of SPIRAPO was found to be highly effective ligand for the reduction of 20 different heterocyclic systems with loadings as low as S/C = 10?000. This dearomatizative hydrogenation provided direct access to optically active tetrahydroquinolines in high enantioselectivities (up to 94percent ee) and excellent yields (up to 99percent), and was used to generate 1.75 g of natural alkaloid (-)-(R)-angustureine. This protocol was subsequently extended to achieve asymmetric hydrogenation of quinoxalines and 2H-1,4-benzoxazin-2-ones in good to excellent enantioselectivities.
Spiroketal-Based C2-Symmetric Scaffold For Asymmetric Catalysis
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Paragraph 0080, (2019/04/08)
Provided herein is a compound of formula (I): wherein each R is independently selected from the group consisting of C1-8 alkyl, C1-8 heteroalkyl having 1-4 heteroatoms independently selected from N, O, and S, C3-6 cycloalkyl, 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S, C6-10 aryl, and 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from N, O, and S; each X is independently selected from OH, PAr2, P(O)Ar2, OPAr2, C3-6 cycloalkyl, 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S or each X together form O2PNR′2; Ar is C6-10aryl; and each R′ is independently selected from hydrogen and C1-8 alkyl. Also provided are methods of making and using the compound of formula (I).
Design, Synthesis, and Application of Chiral C2-Symmetric Spiroketal-Containing Ligands in Transition-Metal Catalysis
Argüelles, Alonso J.,Sun, Siyuan,Budaitis, Brenna G.,Nagorny, Pavel
supporting information, p. 5325 - 5329 (2018/03/27)
We present an expedient and economical route to a new spiroketal-based C2-symmetric chiral scaffold, termed SPIROL. Based on this spirocyclic scaffold, several chiral ligands were generated. These ligands were successfully employed in an array of stereoselective transformations, including in iridium-catalyzed hydroarylations (up to 95 % ee), palladium-catalyzed allylic alkylations (up to 97 % ee), intermolecular palladium-catalyzed Heck couplings (up to 94 % ee), and rhodium-catalyzed dehydroalanine hydrogenation (up to 93 % ee).
Synthesis and SAR study of new hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines as selective topoisomerase IIα-targeting anticancer agents
Magar, Til Bahadur Thapa,Seo, Seung Hee,Kadayat, Tara Man,Jo, Hyunji,Shrestha, Aarajana,Bist, Ganesh,Katila, Pramila,Kwon, Youngjoo,Lee, Eung-Seok
, p. 1909 - 1919 (2018/03/07)
As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesi
