98-91-9Relevant academic research and scientific papers
Ynamide-Mediated Thionoester and Dithioester Syntheses
Yao, Chaochao,Yang, Jinhua,Lu, Xiaobiao,Zhang, Shuyu,Zhao, Junfeng
, p. 6628 - 6631 (2020/09/02)
A novel ynamide-mediated synthesis of thionoesters and dithioesters is described. The selective addition reactions of various monothiocarboxylic acids with ynamide furnish α-thioacyloxyenamides, which undergo transesterification with nucleophilic -OH or -SH species to afford thionoesters and dithioesters, respectively. The broad substrate scope, mild reaction conditions, and excellent yields make this method an attractive synthetic approach to thionoesters and dithioesters.
Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs
Barrow, Andrew S.,Cheng, Yunfei,Gialelis, Timothy L.,Giel, Marie-Claire,Kitamura, Seiya,Li, Gencheng,Moses, John E.,Ottonello, Alessandra,Sharpless, K. Barry,Smedley, Christopher J.,Wolan, Dennis W.
supporting information, p. 12460 - 12469 (2020/06/10)
Diversity Oriented Clicking (DOC) is a unified click-approach for the modular synthesis of lead-like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving “diversity with ease”, by combining classic C?C π-bond click chemistry with recent developments in connective SuFEx-technologies. We showcase 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click-cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click-library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3- and 1,5-dipoles; while reaction with cyclic dienes yields several three-dimensional bicyclic Diels–Alder adducts. Growing the library to 278 discrete compounds through late-stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well-plates—demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.
Controllable thioester-based hydrogen sulfide slow-releasing donors as cardioprotective agents
Yao, Hong,Luo, Shanshan,Liu, Junkai,Xie, Shaowen,Liu, Yanpeng,Xu, Jinyi,Zhu, Zheying,Xu, Shengtao
, p. 6193 - 6196 (2019/06/07)
Hydrogen sulfide (H2S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. However, the study of H2S has been impeded by the lack of appropriate H2S donors that could mimic its slow-releasing process in vivo. Herein, we report the rational design, synthesis, and biological evaluation of a series of thioester-based H2S donors. These cysteine-activated H2S donors release H2S in a slow and controllable manner. Most of the donors comprising an allyl moiety showed significant cytoprotective effects in H9c2 cellular models of oxidative damage. The most potent donor 5e decreased the mitochondrial membrane potential (MMP) loss and lactate dehydrogenase (LDH) release in H2O2-stimulated H9c2 cells. More importantly, donor 5e exhibited a potent cardioprotective effect in an in vivo myocardial infarction (MI) mouse model by reducing myocardial infarct size and cardiomyocyte apoptosis. Taken together, our studies demonstrated that these new allyl thioesters are potential cardioprotective agents by releasing H2S.
Catalyst- and organic solvent-free synthesis of thioacids in water
Elagawany, Mohamed,Hegazy, Lamees,Elgendy
supporting information, p. 2018 - 2021 (2019/07/03)
Thioacids and thioamino acids were synthesized in excellent yields from readily available acyl benzotriazoles and sodium hydrosulfide in water at room temperature. The new methodology features mild reaction conditions, high yields, short reaction times, and does not involve the use of organic solvents or bases. The reaction is eco-friendly, and the workup procedure is simple and does not require chromatographic separation.
Identification of new anti-inflammatory agents based on nitrosporeusine natural products of marine origin
Philkhana, Satish Chandra,Verma, Abhishek Kumar,Jachak, Gorakhnath R.,Hazra, Bibhabasu,Basu, Anirban,Reddy, D. Srinivasa
, p. 89 - 109 (2017/04/26)
Nitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential. Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition, these compounds suppressed several pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), and thereby can be emerged as potent anti-inflammatory compounds. Furthermore, all possible isomers of lead compound 25 were synthesized, characterized and profiled in same set of assays and found that one of the enantiomer (?)-25a was superior among them.
α-Methylphenacyl thioesters as convenient thioacid precursors
Hatanaka, Toru,Yuki, Ryosuke,Saito, Ryota,Sasaki, Kaname
supporting information, p. 10589 - 10592 (2016/11/30)
α-Methylphenacyl (Mpa) thioesters are described as precursors of thioacids. Mpa thioesters are accessible via the condensation of carboxylic acids and phenacyl thiol, which is easily prepared without column chromatography. The Mpa thioesters are selectively deprotected by reduction with zinc dust in the presence of conventional thioacid protecting groups. In addition, the Mpa group exhibits orthogonal reactivity to the Boc group. These features are expected to facilitate the preparation of complex thioacids, including those in peptides.
Sulfo-click reaction via in situ generated thioacids and its application in kinetic target-guided synthesis
Namelikonda, Niranjan Kumar,Manetsch, Roman
supporting information; experimental part, p. 1526 - 1528 (2012/03/11)
Herein, we describe a practical, one-pot variant of the sulfo-click reaction, in which 9-fluorenylmethyl-protected thioesters are rapidly deprotected and reacted further with sulfonylazides to give N-acyl sulfonamides.
FACILE AMIDE FORMATION VIA S-NITROSO THIOACID INTERMEDIATES
-
, (2012/07/31)
Provided are methods for forming a reactive S-nitroso thioacid (NTA), comprising nitrosation of a thioacid with a nitrosation reagent. Also provided are methods for: acylating a nucleophile including selective acylation with a high degree of selectivity toward amines over hydroxyls; amide or peptide bond formation; forming a dipeptide or polypeptide; and peptide coupling/ligation, comprising use of thioacid and amine starting materials, wherein the reactions are mediated by very reactive S-nitroso thioacid (NTA) intermediates enabling extremely fast reactions under mild conditions, providing for broad applications.
A simple method for the conversion of carboxylic acids into thioacids with Lawesson's reagent
Rao, Yu,Li, Xuechen,Nagorny, Pavel,Hayashida, Joji,Danishefsky, Samuel J.
supporting information; scheme or table, p. 6684 - 6686 (2010/01/18)
A one-step protocol for the conversion of carboxylic acids to thioesters, using Lawesson's Reagent, has been developed.
Effects on the reactivity by changing the electrophilic center from C=O to C=S: Contrasting reactivity of hydroxide, p-chlorophenoxide, and butan-2,3-dione monoximate in DMSO/H2O mixtures
Um, Ik-Hwan,Han, Jeong-Yoon,Buncel, Erwin
supporting information; scheme or table, p. 1011 - 1017 (2009/07/18)
Second-order rate constants have been measured spectrophotometrically for the reactions of O-p-nitrophenyl thionobenzoate (1, PNPTB) with HO-, butan-2,3-dione monoximate (Ox-, α-nucleophile), and p-chlorophenoxide (p-ClPhO-, normal nucleophile) in DMSO/H 2O of varying mixtures at (25.0±0.1)°C. Reactivity of these nucleophiles significantly increases with increasing DMSO content. HO - is less reactive than p-ClPhO- toward 1 up to 70 mol % DMSO although HO- is over six pKa units more basic in these media. Ox- is more reactive than p-ClPhO- in all media studied, indicating that the α-effect is in effect. The magnitude of the α-effect (i.e., kox /kp-ClPhO) increases with the DMSO content up to 50 mol% DMSO and decreases beyond that point. However, the dependency of the α-effect profile on the solvent for reactions of 1 contrasts to that reported previously for the corresponding reactions of p-ni-trophenyl benzoate (2, PNPB); reactions of 1 result in much smaller α-effects than those of 2. Breakdown of the α-effect into ground-state (GS) and transition-state (TS) effects shows that the GS effect is not responsible for the α-effect across the solvent mixtures. The role of the solvent has been discussed on the basis of the bell-shaped α-effect profiles found in the current study as well as in our previous studies, that is, a GS effect in the H2O-rich region through H-bonding interactions and a TS effect in the DMSO-rich media through mutual polarizability interactions.
