524-63-0Relevant academic research and scientific papers
Enantioselective 1,6-Conjugate Addition of Dialkyl α-Diazo Methylphosphonate to para-Quinone Methides
Chen, Yuan,Yu, Rui,Wang, Min,Huang, Yanmin,Peng, Yungui
, p. 4856 - 4861 (2021)
An asymmetric 1,6-conjugate addition reaction of dialkyl diazomethylphosphonates to para-quinone methides promoted by phase-transfer catalysis has been developed. A series of chiral diarylmethylated diazomethylphosphonates were accessed with up to 85% yields and 99% ee enantioselectivities. The resulting products were further transformed into bioactive compounds, namely, a chiral dihydrocinnoline phosphonate and a chiral α-aminophosphonate, bearing diarylmethine stereogenic centers. (Figure presented.).
A Cation-Directed Enantioselective Sulfur-Mediated Michael/Mannich Three-Component Domino Reaction involving Chalcones as Michael Acceptors
Ding, Ran,Zheng, Bo,Wang, Yan,Peng, Yungui
, p. 4128 - 4131 (2015)
A new approach has been developed for an asymmetric sulfur-mediated three-component intermolecular Michael/Mannich domino reaction using chalcones as Michael acceptors. This reaction is catalyzed by chiral quaternary ammonium salts derived from modified quinine and provides facile access to complex sulfur-containing compounds with three contiguous stereogenic centers in yields of up to 93%, with 95:5 dr and 95% ee. These compounds were further elaborated to give the equivalent of a chiral aza-Morita-Baylis-Hillman reaction involving chalcones and azetidines bearing four chiral centers.
Antimalarial efficacy of hydroxyethylapoquinine (SN-119) and its derivatives
Sanders, Natalie G.,Meyers, David J.,Sullivan, David J.
, p. 820 - 827 (2014)
Quinine and other cinchona-derived alkaloids, although recently supplanted by the artemisinins (ARTs), continue to be important for treatment of severe malaria. Quinine and quinidine have narrow therapeutic indices, and a safer quinine analog is desirable, particularly with the continued threat of antimalarial drug resistance. Hydroxyethylapoquinine (HEAQ), used at 8 g a day for dosing in humans in the 1930s and halving mortality from bacterial pneumonias, was shown to cure bird malaria in the 1940s and was also reported as treatment for human malaria cases. Here we describe synthesis of HEAQ and its novel stereoisomer hydroxyethylapoquinidine (HEAQD) along with two intermediates, hydroxyethylquinine (HEQ) and hydroxyethylquinidine (HEQD), and demonstrate comparable but elevated antimalarial 50% inhibitory concentrations (IC50) of 100 to 200 nM against Plasmodium falciparum quinine-sensitive strain 3D7 (IC50, 56 nM). Only HEAQD demonstrated activity against quinine-tolerant P. falciparum strains Dd2 and INDO with IC50s of 300 to 700 nM. HEQD had activity only against Dd2 with an IC50 of 313 nM. In the lethal mouse malaria model Plasmodium berghei ANKA, only HEQD had activity at 20 mg/kg of body weight comparable to that of the parent quinine or quinidine drugs measured by parasite inhibition and 30-day survival. In addition, HEQ, HEQD, and HEAQ (IC50>90 μM) have little to no human ether-a-go-go-related gene (hERG) channel inhibition expressed in CHO cells compared to HEAQD, quinine, and quinidine (hERG IC50s of 27, 42, and 4 μM, respectively). HEQD more closely resembled quinine in vitro and in vivo for Plasmodium inhibition and demonstrated little hERG channel inhibition, suggesting that further optimization and preclinical studies are warranted for this molecule. Copyright
A Catalyst-Controlled Enantiodivergent Bromolactonization
Chan, Yuk-Cheung,Lam, Ying-Pong,Tse, Ying-Lung Steve,Wang, Xinyan,Wong, Jonathan,Yeung, Ying-Yeung
supporting information, p. 12745 - 12754 (2021/08/30)
A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed. Quinine-derived amino-amides bearing the same chiral core but different achiral aryl substituents were used as the catalysts. Switching the methoxy substituent in the aryl amide system from meta- to ortho-position results in a complete switch in asymmetric induction to afford the desired lactone in good enantioselectivity and yield. Mechanistic studies, including chemical experiments and density functional theory calculations, reveal that the differences in steric and electronic effects of the catalyst substituent alter the reaction mechanism.
Early and Late Steps of Quinine Biosynthesis
Trenti, Francesco,Yamamoto, Kotaro,Hong, Benke,Paetz, Christian,Nakamura, Yoko,O'Connor, Sarah E.
supporting information, p. 1793 - 1797 (2021/04/05)
The enzymatic basis for quinine 1 biosynthesis was investigated. Transcriptomic data from the producing plant led to the discovery of three enzymes involved in the early and late steps of the pathway. A medium-chain alcohol dehydrogenase (CpDCS) and an esterase (CpDCE) yielded the biosynthetic intermediate dihydrocorynantheal 2 from strictosidine aglycone 3. Additionally, the discovery of an O-methyltransferase specific for 6′-hydroxycinchoninone 4 suggested the final step order to be cinchoninone 16/17 hydroxylation, methylation, and keto-reduction.
Enantioselective γ-Alkylation of α,β-Unsaturated Aldehydes Using New Cinchona-Based Primary Amine Catalyst
Huang, Yong-Shuang,Song, Shuang-Gui,Ren, Lei,Li, You-Gui,Wu, Xiang
supporting information, p. 6838 - 6841 (2019/11/11)
New cinchona-based primary amine catalysts were prepared and screened as organocatalysts for the γ-alkylation of α,β-unsaturated aldehydes with bis(4-dimethylaminophenyl)methanol. Catalyst C3 containing acetic acid group yielded γ-alkylated products in good yields (up to 94 %) with up to 90 % ee. This new primary aminocatalyst provide new opportunities to explore novel asymmetric transformations.
Organocatalytic Nitroaldol Reaction Associated with Deuterium-Labeling
Yamada, Tsuyoshi,Kuwata, Marina,Takakura, Ryoya,Monguchi, Yasunari,Sajiki, Hironao,Sawama, Yoshinari
supporting information, p. 637 - 641 (2017/12/13)
A deuterium-labeling reaction of nitroalkanes in deuterium oxide and the subsequent nitroaldol reaction have been accomplished under basic and organocatalytic conditions to provide the deuterium-labeled β-nitroalcohols in high yields and high deuterium contents. β-Deuterated β-nitroalcohols could be smoothly obtained from the reaction of nitroalkanes and various electrophiles using the easily-removal basic resin WA30. Furthermore, the asymmetric nitroaldol reaction using nitromethane and α-keto esters as electrophiles in the presence of a quinine-derived organocatalyst in deuterium oxide could provide the desired β-deuterated nitroalcohol derivatives with high enantioselectivities. (Figure presented.).
DERIVATIVES OF QUINOLINE AS INHIBITORS OF DYRK1A AND/OR DYRK1B KINASES
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Paragraph 0503-0504, (2018/07/15)
The present invention relates to the compound of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof. The present invention is further concerned with the use of such a compound or salt, stereoisomer, tautomer or N-oxide thereof as medicament and a pharmaceutical composition comprising said compound.
Enantioselective Spirocyclopropanation of para-Quinone Methides Using Ammonium Ylides
Roiser, Lukas,Waser, Mario
supporting information, p. 2338 - 2341 (2017/05/12)
The use of Cinchona alkaloid-based chiral ammonium ylides allows for the first highly enantioselective and broadly applicable spirocyclopropanation reactions of para-quinone methides. This strategy provides a straightforward protocol toward the chiral spiro[2.5]octa-4,7-dien-6-one skeleton, which is a frequently found structural motif in important biologically active molecules.
Asymmetric Alkylation of Anthrones, Enantioselective Total Synthesis of (?)- and (+)-Viridicatumtoxins B and Analogues Thereof: Absolute Configuration and Potent Antibacterial Agents
Nicolaou,Liu, Guodu,Beabout, Kathryn,McCurry, Megan D.,Shamoo, Yousif
supporting information, p. 3736 - 3746 (2017/03/20)
A phase transfer catalyzed asymmetric alkylation of anthrones with cyclic allylic bromides using quinidine- or quinine-derived catalysts is described. Utilizing mild basic conditions and as low as 0.5 mol % catalyst loading, and achieving up to >99:1 dr selectivity, this asymmetric reaction was successfully applied to produce enantioselectively (?)- and (+)-viridicatumtoxins B, and thus allowed assignment of the absolute configuration of this naturally occurring antibiotic. While the developed asymmetric synthesis of C10 substituted anthrones is anticipated to find wider applications in organic synthesis, its immediate application to the construction of a variety of designed enantiopure analogues of viridicatumtoxin B led to the discovery of highly potent, yet simpler analogues of the molecule. These studies are expected to facilitate drug discovery and development efforts toward new antibacterial agents.
