- PD-1/PD-L1 INHIBITORS
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Compounds and methods of using said compounds singly or in combination with additional agents and compositions of said compounds for the treatment of cancer are disclosed Formula (I)
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- Zr-mediated synthesis of chiral cyclic imines and their application in Betti reactions
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[Figure not available: see fulltext.] A novel synthetic strategy has been outlined to assemble enantiomerically pure Betti bases with unprecedented structures. This involves the Zr-mediated reduction of pyrrolidin-2-ones to cyclic imines and their subsequent reaction with phenolic derivatives.
- Speich, Elena,Banfi, Luca,Moni, Lisa,Riva, Renata,Rocca, Valeria,Basso, Andrea
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p. 329 - 333
(2018/05/28)
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- Synthesis of a series of ω-dimethylaminoalkyl substituted ethylenediamine ligands for use in enantioselective catalysis
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The title compounds H2NCH((CH2)nNMe2)CH2NH2 L1-L4 (n = 1-4) are efficiently synthesized in enantiopure form. The commercial starting materials, l-asparagine, (S)-5-hydroxymethyl-2-pyrrolidinone, and (S)-6-(((benzyloxy)carbonyl)-amino)-2-((tert-butoxycarbonyl)amino)hexanoic acid, are elaborated in 6-9 standard steps to give L1 (18% overall), L2 (13%), L3 (36%) and L4 (38%) or the corresponding tris(hydrochloric acid) salts [H3NCH((CH2)nNHMe2)CH2NH3]3+ 3Cl-, which are preferable for long term storage. The sequences make use of isobutyl carbamate, Cbz, and Boc protecting groups and Hofmann type rearrangements; the dimethylamino groups are introduced at late stages, either via reductive dimethylations or nucleophilic displacements involving mesylates and HNMe2. L1-L4 chelate to [Co(en)2]3+ fragments to give octahedral complexes that catalyze numerous enantioselective reactions.
- Ghosh, Subrata K.,Ganzmann, Carola,Gladysz, John A.
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p. 1273 - 1280
(2015/11/09)
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- TRANSITION METAL COMPLEXES FOR ENANTIOSELECTIVE CATALYSIS OF CARBON-CARBON, CARBON-HETEROATOM, AND CARBON-HYDROGEN BOND FORMING REACTIONS
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In some embodiments, the present disclosure pertains to a compound, comprising a transition metal complex having the formula Φ-[Μ (x,y)-L1 (w,v)-L2 (t,u)-L3]p+An-mZ-p_m. In an embodiment of the present disclosure Φ may be A. In another embodiment Φ may be Δ. In some embodiments of the present disclosure, M is a transition metal. In a related embodiment, p is an integer corresponding to the oxidation state of M. In some embodiments of the present disclosure, each of x, y, w, v, t, and u independently comprise R. In other embodiments, each of x, y, w, v, t, and u independently comprise S. In an embodiment of the present disclosure, each of L1, L2, and L3 independently is a ligand comprising a substituted diamine. In some embodiments, An" comprises a lipophilic anion, where m is from 1 to 3, and where Z- comprises an optional second anion.
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- Late-stage diversification of chiral N-heterocyclic-carbene precatalysts for enantioselective homoenolate additions
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A library of chiral triazolium salts has been prepared by late-state diversification of a triazolium amine salt. By utilizing a primary amine as a functional handle, a single triazolium salt can be transformed into a variety of chiral N-heterocyclic carbene precatalysts. This approach makes the preparation of chiral N-heterocyclic carbenes possible by a single-step modification of a triazolium salt, rather than the usual need for multistep organic synthesis and challenging heterocycle formation for each member of a catalyst library. We have screened these catalysts for control of diastereo- and enantioselectivity in a γ-lactam-forming reaction between α,β-unsaturated aldehydes and cyclic ketimines. Saving the best for last: Enantioselective homoenolate additions have been hindered by the challenge of synthesizing N-mesityl-substituted azolium salts. A library of pyrrole-functionalized chiral triazolium salts was prepared by direct modification of the preformed azolium core. Copyright
- Zheng, Pinguan,Gondo, Chenaimwoyo A.,Bode, Jeffrey W.
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p. 614 - 620
(2011/10/12)
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- Probing the functional requirements of the L-haba side-chain of amikacin - Synthesis, 16S A-site rRNA binding, and antibacterial activity
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The l-amino group in amikacin was acylated with a variety of 2-hydroxy aminocarboxylic acids to probe the effect of acylation on ribosomal binding and antibacterial activity. The N-hydroxy urea analogue of amikacin (8a) in which the 2-S-hydroxyl-bearing carbon was replaced by an N-OH group was equally active against S. aureus and E. coli in vitro. The analogous tobramycin variant 9 was more active than amikacin.
- Hanessian, Stephen,Kornienko, Alexander,Swayze, Eric E.
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p. 995 - 1007
(2007/10/03)
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- Synthesis of chiral 1,2,4-triaminobutanes
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(S)-5-(Azidomethyl)-2-pyrrolidone, obtained by the Mitsunobu reaction, was reduced to (S)-5-(aminomethyl)-2-pyrrolidone which was hydrolysed to (S)-4,5-diaminovaleric acid. The acid, after acylation with i-butyl or with (1R, 3R, 4S)-menthyl chloroformate, underwent a Curtius reaction yielding the corresponding (S)-1,2-dialkoxycarbonyl-1,2,4-triaminobutane. Alternatively, (S)-5-(aminomethyl)-2-pyrrolidone was subjected to exhaustive t-butoxycarbonylation followed by ring-cleavage with ammonia to give (S)-N4,N5,N5-triboc-4,5-diaminovaleramide and was converted by a Hofmann rearrangement to (S)-N1,N2-di-t-butoxy carbonyl-4-methoxycarbonyl-1,2,4-triaminobutane.
- Altman,Ben-Ishai
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