158807-47-7Relevant academic research and scientific papers
Chiral N,N′-Dioxide/Tm(OTf)3 Complex-Catalyzed Asymmetric Bisvinylogous Mannich Reaction of Silyl Ketene Acetal with Aldimines
Zou, Sijia,Li, Weiwei,Fu, Kai,Cao, Weidi,Lin, Lili,Feng, Xiaoming
supporting information, p. 2295 - 2300 (2019/04/16)
An enantioselective bisvinylogous Mannich reaction of silyl ketene acetal with aldimines has been realized by using a chiral N,N′-dioxide/Tm(OTf)3 complex as catalyst, providing an effective method to synthesize chiral ζ-amino-α,β,γ,δ-unsaturated carbonyl compounds. (Figure presented.).
Identification of Selective Dual ROCK1 and ROCK2 Inhibitors Using Structure-Based Drug Design
Hobson, Adrian D.,Judge, Russell A.,Aguirre, Ana L.,Brown, Brian S.,Cui, Yifang,Ding, Ping,Dominguez, Eric,Digiammarino, Enrico,Egan, David A.,Freiberg, Gail M.,Gopalakrishnan, Sujatha M.,Harris, Christopher M.,Honore, Marie P.,Kage, Karen L.,Kapecki, Nicolas J.,Ling, Christopher,Ma, Junli,Mack, Helmut,Mamo, Mulugeta,Maurus, Stefan,McRae, Bradford,Moore, Nigel S.,Mueller, Bernhard K.,Mueller, Reinhold,Namovic, Marian T.,Patel, Kaushal,Pratt, Steve D.,Putman, C. Brent,Queeney, Kara L.,Sarris, Kathy K.,Schaffter, Lisa M.,Stoll, Vincent,Vasudevan, Anil,Wang, Lei,Wang, Lu,Wirthl, William,Yach, Kimberly
, p. 11074 - 11100 (2019/01/04)
A HTS campaign identified compound 1, an excellent hit-like molecule to initiate medicinal chemistry efforts to optimize a dual ROCK1 and ROCK2 inhibitor. Substitution (2-Cl, 2-NH2, 2-F, 3-F) of the pyridine hinge binding motif or replacement with pyrimidine afforded compounds with a clean CYP inhibition profile. Cocrystal structures of an early lead compound were obtained in PKA, ROCK1, and ROCK2. This provided critical structural information for medicinal chemistry to drive compound design. The structural data indicated the preferred configuration at the central benzylic carbon would be (R), and application of this information to compound design resulted in compound 16. This compound was shown to be a potent and selective dual ROCK inhibitor in both enzyme and cell assays and efficacious in the retinal nerve fiber layer model after oral dosing. This tool compound has been made available through the AbbVie Compound Toolbox. Finally, the cocrystal structures also identified that aspartic acid residues 176 and 218 in ROCK2, which are glutamic acids in PKA, could be targeted as residues to drive both potency and kinome selectivity. Introduction of a piperidin-3-ylmethanamine group to the compound series resulted in compound 58, a potent and selective dual ROCK inhibitor with excellent predicted drug-like properties.
Direct Asymmetric Vinylogous and Bisvinylogous Mannich-Type Reaction Catalyzed by a Copper(I) Complex
Zhang, Hai-Jun,Shi, Chang-Yun,Zhong, Feng,Yin, Liang
supporting information, p. 2196 - 2199 (2017/02/23)
A direct catalytic asymmetric vinylogous Mannich-type reaction has been disclosed in good yield, excellent regio-, diastereo- and enantioselectivity. The key to control the regioselectivity is the combination of a bulky N-acylpyrazole and a bulky bisphosphine ligand. The catalytic system was extended to a bisvinylogous Mannich-type reaction by changing the ligand. The synthetic utility of the vinylogous products was demonstrated by several transformations.
Regio- and enantioselective Pd-catalyzed allylic amination of monosubsti-tuted allylic substrates with BocNHOMe
Zheng, Bao-Hui,Ding, Chang-Hua,Hou, Xue-Long
supporting information; experimental part, p. 2262 - 2264 (2011/10/19)
A new type of N-nucleophile has been developed in Pd-catalyzed asymmetric allylic amination with monosubstituted allyl substrates, affording corresponding branched allyl amines in high regio- and enantioselectivities. Either OMe or Boc group in products can be removed easily to provide primary amine derivatives with the optical purity unchanged. Georg Thieme Verlag Stuttgart - New York.
Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs
Carocci, Alessia,Catalano, Alessia,Bruno, Claudio,Lentini, Giovanni,Franchini, Carlo,De Bellis, Michela,De Luca, Annamaria,Camerino, Diana Conte
experimental part, p. 299 - 307 (2010/10/21)
New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated
Which is the actual catalyst: Chiral phosphoric acid or chiral calcium phosphate?
Hatano, Manabu,Moriyama, Katsuhiko,Maki, Toshikatsu,Ishihara, Kazuaki
supporting information; experimental part, p. 3823 - 3826 (2010/08/22)
(Figure Presented) Both catalysts work: A highly enantioselective direct Mannich-type reaction of NBoc-protected aldimines with 1,3-dicarbonyl compounds has been developed with the use of a chiral phosphoric acid in the presence or absence of Ca . The absolute stereoselectivity of the phosphoric acid catalysis was found to be opposite to that of the calcium phosphate catalysis (see scheme; Boc = tert-butoxycarbonyl).
Highly practical BINOL-derived acid-base combined salt catalysts for the asymmetric direct mannich-type reaction
Hatano, Manabu,Ishihara, Kazuaki
scheme or table, p. 3785 - 3801 (2011/02/16)
The catalytic asymmetric direct Mannich-type reaction between aldimines and 1,3-dicarbonyl compounds is one of the most important carbon-carbon bond-forming reactions in organic chemistry. The resulting Mannich adducts can be efficiently transformed into pharmaceutically useful, optically active -amino ketones, -amino esters, -lactams, etc. In the course of our study of chiral acid-base combined salt catalysts for asymmetric reactions, we developed a series of simple, practical, chiral BINOL-derived salt catalysts, such as chiral pyridinium 1,1-binaphthyl-2,2-disulfonates 1, chiral lithium(I) binaphtholate 2, chiral magnesium(II) binaphtholate (3), chiral calcium(II) phosphate 4, and chiral phosphoric acid 5, which were particularly effective for direct Mannich-type reactions. 1 Introduction 2 1,1-Binaphthyl-2,2-disulfonic Acid (BINSA)-Pyridinium Salts 3 Lithium(I) Binaphtholate Salts 4 Magnesium(II) Binaphtholate Salts 5 Calcium(II) Phosphate Salts and Chiral Phosphoric Acids 6 Conclusions. Georg Thieme Verlag Stuttgart · New York.
Oxazinanones as chiral auxiliaries: Synthesis and evaluation in enolate alkylations and aldol reactions
Davies, Stephen G.,Garner, A. Christopher,Roberts, Paul M.,Smith, Andrew D.,Sweet, Miles J.,Thomson, James E.
, p. 2753 - 2768 (2008/02/10)
Homochiral β-amino esters (prepared on multigram scale by lithium amide conjugate addition) are readily transformed into oxazinanones. N-Acyl derivatives of oxazinanones undergo stereoselective enolate alkylation reactions, with higher stereoselectivities observed for the enolate alkylation of (R)-N-propanoyl-4-iso-propyl-6,6-dimethyl-oxazinan-2-one than the corresponding Evans oxazolidin-2-one. A C(4)-iso-propyl stereodirecting group within the oxazinanone conveys higher stereoselectivity than the analogous C(4)-phenyl substituent. gem-Dimethyl substitution at C(6) within the oxazinanone framework facilitates exclusive exocyclic cleavage upon hydrolysis to furnish α-substituted carboxylic acid derivatives and the parent oxazinanone in good yield. Asymmetric aldol reactions of a range of aromatic and aliphatic aldehydes with the chlorotitanium enolate of (R)-N-propanoyl-4-iso- propyl-6,6-dimethyl-oxazinan-2-one proceed with excellent diastereoselectivity. Hydrolysis of the aldol products affords homochiral α-methyl-β- hydroxy-carboxylic acids. The Royal Society of Chemistry 2006.
