133467-01-3Relevant articles and documents
N-1 BRANCHED ALKYL SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Page/Page column 65, (2020/12/29)
Imidazo[4,5-c]quinoline compounds having a substituent that is attached at the N-1 position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds are disclosed. Methods of use of the compounds as immune response modifiers, for inducing (or inhibiting) cytokine biosynthesis in humans and animals, and in the treatment of diseases including infectious and neoplastic diseases are also disclosed.
Isolation, Structure Elucidation, and (Bio)Synthesis of Haprolid, a Cell-Type-Specific Myxobacterial Cytotoxin
Steinmetz, Heinrich,Li, Jun,Fu, Chengzhang,Zaburannyi, Nestor,Kunze, Birgitte,Harmrolfs, Kirsten,Schmitt, Viktoria,Herrmann, Jennifer,Reichenbach, Hans,H?fle, Gerhard,Kalesse, Markus,Müller, Rolf
supporting information, p. 10113 - 10117 (2016/08/16)
Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound.
A simple, rapid, and efficient N-Boc protection of amines under ultrasound irradiation and catalyst-free conditions
Amira, Aicha,K'Tir, Hacene,Berredjem, Malika,Aouf, Nour-Eddine
, p. 509 - 515 (2014/03/21)
A green and simple approach for the N-Boc protection on structurally diverse amines under ultrasound irradiation is described. Selective N-Boc protection was achieved in excellent isolated yield in a short reaction time at room temperature. Mild conditions, inexpensive and an easily available reagent, and absence of any auxiliary substances are the main advantages of this procedure. Graphical abstract: [Figure not available: see fulltext.]
Substituted 7-amino-5-thio-thiazolo[4,5- d ]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1)
Karlstr?m, Sofia,Nordvall, Gunnar,Sohn, Daniel,Hettman, Andreas,Turek, Dominika,?hlin, Kristofer,Kers, Annika,Claesson, Martina,Slivo, Can,Lo-Alfredsson, Yvonne,Petersson, Carl,Bessidskaia, Galina,Svensson, Per H.,Rein, Tobias,Jerning, Eva,Malmberg, ?sa,Ahlgen, Charlotte,Ray, Colin,Vares, Lauri,Ivanov, Vladimir,Johansson, Rolf
supporting information, p. 3177 - 3190 (2013/06/05)
We have developed two parallel series, A and B, of CX3CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]pyrimidine core structure, we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with α-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX3CR1 antagonists.
Highly modular P-OP ligands for asymmetric hydrogenation: Synthesis, catalytic activity, and mechanism
Fernandez-Perez, Hector,Donald, Steven M. A.,Munslow, Ian J.,Benet-Buchholz, Jordi,Maseras, Feliu,Vidal-Ferran, Anton
supporting information; experimental part, p. 6495 - 6508 (2010/10/02)
A library of enantiomerically pure P-OP ligands (phosphine-phosphite), straightforwardly available in two synthetic steps from enantiopure Sharpless epoxy ethers is reported. Both the alkyloxy and phosphite groups can be optimized for maximum enantioselectivity and catalytic activity. Their excellent performance in the Rhcatalyzed asymmetric hydrogenation of a wide variety of functionalized alkenes (26 examples) and modular design makes them attractive for future applications. The lead catalyst incorporates an (S)-BINOL-derived (BINOL= 1,1'bi-2-naphthol) phosphite group with computational studies revealing that this moiety has a dual effect on the behavior of our P-OP ligands. On one hand, the electronic properties of phosphite hinder the binding and reaction of the substrate in two out of the four possible manifolds. On the other hand, the steric effects of the BINOL allow for discrimination between the two remaining manifolds, thereby elucidating the high efficiency of these catalysts.
Enzymatic approach to both enantiomers of N-Boc hydrophobic amino acids
Agosta, Eleonora,Caligiuri, Antonio,D'Arrigo, Paola,Servi, Stefano,Tessaro, Davide,Canevotti, Renato
, p. 1995 - 1999 (2007/10/03)
Protease catalysed hydrolysis of N-Boc-amino acid esters allows us to obtain N-Boc l-acids and d-esters of amino butanoic acid, nor-leucine, nor-valine, leucine and t-leucine in excellent ee. The reaction occurs in short reaction times and high concentrations. When a biphasic system (buffer-MTBE) is employed, a strong solvent effect is observed. This method could be of significance for the preparation of d-t-leucine, for which a practical method is currently unavailable.
Asymmetric synthesis of α-amino acids through α-iodination of chiral unsaturated carboxamides and stereoselective iodolactonization
Kitagawa, Osamu,Hanano, Tokushi,Kikuchi, Norihiko,Taguchi, Takeo
, p. 2165 - 2168 (2007/10/02)
The α-iodination reaction of chiral enamides 1 possessing (2R,5R)-2,5-bis(methoxymethyl) pyrrolidine as a chiral auxiliary proceeded with high diastereoselectivity in the presence of I2 and s-collidine. The chiral iodides 2 thus obtained were converted to the α-BocNH-amides 3 without epimerization. The subsequent iodolactonization afforded trans-lactones 4 with a relatively high selectivity.
New Methods and Reagents in Organic Synthesis. 67. A General Synthesis of Derivatives of Optically Pure 2-(1-Aminoalkyl)thiazole-4-carboxylic Acids
Hamada, Yasumasa,Shibata, Makoto,Sugiura, Tsuneyuki,Kato, Shinji,Shioiri, Takayuki
, p. 1252 - 1255 (2007/10/02)
Preparations of 2-(1-aminoalkyl)thiazole-4-carboxylic acids (thiazole amino acids), important constituents of a series of cytotoxic cyclic peptides from marine organisms, have been conveniently and efficiently achieved as their N- and C-protected derivatives 6 from N-Boc or N-Z α-amino acids 1 in five steps.Esterification of 1 with methyl iodide followed by reduction with lithium chloride-sodium borohydride afforded N-protected amino alcohols 3.Selective reduction of the α-ester functions of the glutamic acid derivatives (Z-D- and Z-L-Glu(O-t-Bu)-OMe and O-t-Bu) was also achieved under the above reduction conditions.Dimethyl sulfoxide oxidation, followed by condensation with cysteine methyl ester afforded the thiazolidine derivatives 5, which were conveniently dehydrogenated with manganese dioxide, called chemical manganese dioxide (CMD) and produced for batteries, to give the desired thiazole amino acid derivetives 6.The glutamine derivatives (Z-D- and Z-L-(gln)Thz-OMe) were prepared from the corresponding glutamic acid derivatives (Z-D- and Z-L-6f).No appreciable racemization was observed in the above conversion, which was proven by HPLC of the 3,5-dinitrobenzoyl derivatives of thiazole amino acids 6 using a chiral column.
