77449-94-6Relevant articles and documents
A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors
Tian, Yinping,Jin, Jin,Wang, Congying,Lv, Wenhui,Li, Xuewei,Che, Xiaona,Gong, Yanchao,Li, Yanjun,Li, Quanli,Hou, Jingli,Wang, Peng G.,Shen, Jie
supporting information, p. 2434 - 2437 (2016/07/07)
This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.
Proline editing: A general and practical approach to the synthesis of functionally and structurally diverse peptides. Analysis of steric versus stereoelectronic effects of 4-substituted prolines on conformation within peptides
Pandey, Anil K.,Naduthambi, Devan,Thomas, Krista M.,Zondlo, Neal J.
supporting information, p. 4333 - 4363 (2013/05/08)
Functionalized proline residues have diverse applications. Herein we describe a practical approach, proline editing, for the synthesis of peptides with stereospecifically modified proline residues. Peptides are synthesized by standard solid-phase peptide synthesis to incorporate Fmoc-hydroxyproline (4R-Hyp). In an automated manner, the Hyp hydroxyl is protected and the remainder of the peptide synthesized. After peptide synthesis, the Hyp protecting group is orthogonally removed and Hyp selectively modified to generate substituted proline amino acids, with the peptide main chain functioning to "protect" the proline amino and carboxyl groups. In a model tetrapeptide (Ac-TYPN-NH2), 4R-Hyp was stereospecifically converted to 122 different 4-substituted prolyl amino acids, with 4R or 4S stereochemistry, via Mitsunobu, oxidation, reduction, acylation, and substitution reactions. 4-Substituted prolines synthesized via proline editing include incorporated structured amino acid mimetics (Cys, Asp/Glu, Phe, Lys, Arg, pSer/pThr), recognition motifs (biotin, RGD), electron-withdrawing groups to induce stereoelectronic effects (fluoro, nitrobenzoate), handles for heteronuclear NMR (19F:fluoro; pentafluorophenyl or perfluoro-tert-butyl ether; 4,4-difluoro; 77SePh) and other spectroscopies (fluorescence, IR: cyanophenyl ether), leaving groups (sulfonate, halide, NHS, bromoacetate), and other reactive handles (amine, thiol, thioester, ketone, hydroxylamine, maleimide, acrylate, azide, alkene, alkyne, aryl halide, tetrazine, 1,2-aminothiol). Proline editing provides access to these proline derivatives with no solution-phase synthesis. All peptides were analyzed by NMR to identify stereoelectronic and steric effects on conformation. Proline derivatives were synthesized to permit bioorthogonal conjugation reactions, including azide-alkyne, tetrazine-trans-cyclooctene, oxime, reductive amination, native chemical ligation, Suzuki, Sonogashira, cross-metathesis, and Diels-Alder reactions. These proline derivatives allowed three parallel bioorthogonal reactions to be conducted in one solution.
A general approach for preparation of polymer-supported chiral organocatalysts via acrylic copolymerization
Kristensen, Tor E.,Vestli, Kristian,Jakobsen, Martin G.,Hansen, Finn K.,Hansen, Tore
supporting information; experimental part, p. 1620 - 1629 (2010/04/29)
(Figure Presented) Polymer-supported chiral organocatalysts, as well as most other forms of immobilized catalysts, are traditionally prepared by a postmodification approach where modified catalyst precursors are anchored onto prefabricated polymer beads. Herein, we report an alternative and more scalable approach where polymer-supported chiral enamine and iminium organocatalysts are prepared in a bottom-up fashion where methacrylic functional monomers are prepared in an entirely nonchromatographic manner and subsequently copolymerized with suitable comonomers to give cross-linked polymer beads. All syntheses have been conducted on multigram scale for all intermediates and finished polymer products, and the catalysts have proven successful in reactions taking place in solvents spanning a wide range of solvent polarity. While polymer-supported proline and prolineamides generally demonstrated excellent results and recycling robustness in asymmetric aldol reactions of ketones and benzaldehydes, the simplest type of Joargensen/Hayashi diarylprolinol TMS-ether showed excellent selectivity, but rather sluggish reactivity in the Enders-type asymmetric cascade. The polymer-supported version of the first-generation MacMillan imidazoHdinone had a pattern of reactivity very similar to that of the monomeric catalyst, but is too unstable to allow recycling.
