Sugar-Modified Uridine Bisvinyl Sulfone:  Synthesis of a Bifunctionalized Nucleoside Michael Acceptor and Its Use in Stereoselective Tandem Cyclization†

1998 ◽  
Vol 63 (6) ◽  
pp. 1754-1760 ◽  
Author(s):  
Sanjib Bera ◽  
Graham J. Langley ◽  
Tanmaya Pathak
Keyword(s):  
Michael Acceptor ◽  
Tandem Cyclization

scholarly journals New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 97
Author(s):  
Shamsunnahar Khushi ◽  
Angela A. Salim ◽  
Ahmed H. Elbanna ◽  
Laizuman Nahar ◽  
Robert J. Capon
Keyword(s):  
Marine Sponge ◽  
Tissue Specificity ◽  
Spectroscopic Analysis ◽  
Transformation Products ◽  
Chemical Fractionation ◽  
Cancer Tissue ◽  
Michael Acceptor ◽  
Michael Acceptors ◽  
Stable Ring

Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a–1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1′,8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a–1n. Where the 1′,8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a–1b, and 1h–1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c–1g, and 1k–1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.

scholarly journals Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 890
Author(s):  
Joel K. Annor-Gyamfi ◽  
Ebenezer Ametsetor ◽  
Kevin Meraz ◽  
Richard A. Bunce
Keyword(s):  
Aromatic Ring ◽  
Aromatic Amines ◽  
Control Experiment ◽  
Ring Closure ◽  
Domino Reaction ◽  
Side Chain ◽  
Initial Reaction ◽  
Dual Reactivity ◽  
Michael Acceptor ◽  
Nitrogen Nucleophile

An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to an acrylate or acrylonitrile aza-Michael acceptor as well as an aromatic ring activated toward SNAr ring closure. A control experiment established that the initial reaction was an SN2′-type displacement of the side chain acetate by the amine to generate the alkene product with the added nitrogen nucleophile positioned trans to the SNAr aromatic ring acceptor. Thus, equilibration of the initial alkene geometry is required prior to cyclization. A further double bond migration was observed for several reactions targeting dihydronaphthyridines from substrates with a side chain acrylonitrile moiety. MBH acetates incorporating a 2,5-difluorophenyl moiety were found to have dual reactivity in these annulations. In the absence of O2, the expected dihydroquinolines were formed, while in the presence of O2, quinolones were produced. All of the products were isolated in good to excellent yields (72–93%). Numerous cases (42) are reported, and mechanisms are discussed.

Proteasome selectivity towards Michael acceptor containing oligopeptide-based inhibitors

2010 ◽  
Vol 8 (8) ◽  
pp. 1885 ◽  
Author(s):  
Wouter A. van der Linden ◽  
Paul P. Geurink ◽  
Chris Oskam ◽  
Gijsbert A. van der Marel ◽  
Bogdan I. Florea ◽  
...  
Keyword(s):  
Michael Acceptor

scholarly journals The TvLEGU-1, a Legumain-Like Cysteine Proteinase, Plays a Key Role inTrichomonas vaginalisCytoadherence

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Francisco Javier Rendón-Gandarilla ◽  
Lucero de los Angeles Ramón-Luing ◽  
Jaime Ortega-López ◽  
Ivone Rosa de Andrade ◽  
Marlene Benchimol ◽  
...  
Keyword(s):  
Proteolytic Activity ◽  
Virulence Factor ◽  
Trichomonas Vaginalis ◽  
Potential Role ◽  
Polyclonal Antibodies ◽  
Cysteine Proteinase ◽  
Two Dimensional ◽  
Cell Binding ◽  
Vaginal Secretions ◽  
Michael Acceptor

The goal of this paper was to characterize aTrichomonas vaginaliscysteine proteinase (CP) legumain-1 (TvLEGU-1) and determine its potential role as a virulence factor duringT. vaginalisinfection. A 30-kDa band, which migrates in three protein spots (pI~6.3, ~6.5, and ~6.7) with a different type and level of phosphorylation, was identified as TvLEGU-1 by one- and two-dimensional Western blot (WB) assays, using a protease-rich trichomonad extract and polyclonal antibodies produced against the recombinant TvLEGU-1 (anti-TvLEGU-1r). Its identification was confirmed by mass spectrometry. Immunofluorescence, cell binding, and WB assays showed that TvLEGU-1 is upregulated by iron at the protein level, localized on the trichomonad surface and in lysosomes and Golgi complex, bound to the surface of HeLa cells, and was found in vaginal secretions. Additionally, the IgG and Fab fractions of the anti-TvLEGU-1r antibody inhibited trichomonal cytoadherence up to 45%. Moreover, the Aza-Peptidyl Michael Acceptor that inhibited legumain proteolytic activity in live parasites also reduced levels of trichomonal cytoadherence up to 80%. In conclusion, our data show that the proteolytic activity of TvLEGU-1 is necessary for trichomonal adherence. Thus, TvLEGU-1 is a novel virulence factor upregulated by iron. This is the first report that a legumain-like CP plays a role in a pathogen cytoadherence.

scholarly journals Palladium-Catalyzed Tandem Cyclization/Suzuki Coupling of 1,6-Enynes: Reaction Scope and Mechanism.

ChemInform ◽  
2005 ◽  
Vol 36 (31) ◽  
Author(s):  
Gangguo Zhu ◽  
Xiaofeng Tong ◽  
Jiang Cheng ◽  
Yanhui Sun ◽  
Dao Li ◽  
...  
Keyword(s):  
Suzuki Coupling ◽  
Palladium Catalyzed ◽  
Tandem Cyclization

PTSA-catalyzed tandem cyclization protocol for the stereoselective total synthesis of obolactone

2010 ◽  
Vol 51 (17) ◽  
pp. 2295-2296 ◽  
Author(s):  
Palakodety Radha Krishna ◽  
Palabindela Srinivas
Keyword(s):  
Total Synthesis ◽  
Tandem Cyclization
Sign in / Sign up

Export Citation Format

Share Document