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Synthesis And Biological Evaluation Of A 2-aryl Polyhydroxylated Pyrrolidine Alkaloid-based Library.
En-Lun Tsou, Sih-Yu Chen, M. Yang, S. Wang, Ting-Ren Rachel Cheng, W. Cheng
Published 2008 · Chemistry, Medicine
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Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly, 15 and 19 show better inhibitory activities than radicamine A (20) and B (18) against alpha-glucosidases. The IC(50) values of 15 and 19 are 1.1 and 0.5 microM, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases.
This paper references
Practical and highly stereoselective approaches to the total synthesis of (−)-codonopsinine
S. Chandrasekhar (2006)
Polyhydroxylated Alkaloids with Lipophilic Moieties as Glycosidase Inhibitors from Higher Plants
G. Kusano (2002)
Skeletal diversity via a branched pathway: efficient synthesis of 29 400 discrete, polycyclic compounds and their arraying into stock solutions.
O. Kwon (2002)
Combinatorial chemistry and contemporary pharmacology.
J. Lazo (2000)
Synthesis and Applications of Small Molecule Libraries.
L. A. Thompson (1996)
Synthesis and glycosidase inhibitory activity of 7-deoxycasuarine
Ana T Carmona (2003)
Total synthesis of (+)-hyacinthacine A2 based on SmI2-induced nitrone umpolung.
S. Desvergnes (2005)
Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases
J. Rountree (2007)
Polyhydroxylated alkaloids -- natural occurrence and therapeutic applications.
A. Watson (2001)
L-nucleoside enantiomers as antivirals drugs: a mini-review.
C. Mathé (2006)
Synthesis and high-throughput screening of N-acetyl-beta-hexosaminidase inhibitor libraries targeting osteoarthritis.
J. Liu (2004)
Organometal additions to alpha-iminoesters: N-alkylation via umpolung.
J. S. Dickstein (2008)
From Liana to a Glycotechnology Tool, 25 Years of 2,5-Imino-2,5-dideoxy-imino-D-mannitol (DMDP)
T. Wrodnigg (2002)
Total synthesis of lamellarins D, L, and N
Naotaka Fujikawa (2006)
New alkaloid from the aerial parts of Codonopsis clematidea
Shunsuke Ishida (2007)
Carbon-carbon bond-forming solid-phase reactions. Part II.
R. E. Sammelson (2001)
Solution-phase parallel synthesis of highly diverse spiroisoxazolinohydantoins
Hao-Wei Shih (2008)
Biological properties of D- and L-1-deoxyazasugars.
A. Kato (2005)
HECK REACTION OF ENDOCYCLIC ENECARBAMATES WITH DIAZONIUM SALTS. FORMAL ENANTIOSELECTIVE SYNTHESES OF ALKALOIDS (-)-CODONOPSINE AND (-)-CODONOPSININE, AND THE SYNTHESIS OF A NEW C-ARYL AZASUGAR
D. F. Oliveira (1999)
Total syntheses of hyacinthacine A2 and 7-deoxycasuarine by cycloaddition to a carbohydrate derived nitrone
F. Cardona (2003)
The synthesis of chiral annulet 1,4,7-triazacyclononanes
G. Argouarch (2002)
SYNTHESIS AND REACTIONS OF CHIRAL CYCLIC NITRONES DERIVED FROM D-RIBOSE
C. W. Holzapfel (1998)
Total synthesis of (−)-radicamine B
M. K. Gurjar (2006)
α- and β-Glucosidase inhibitors: chemical structure and biological activity
Eduardo B. de Melo (2006)
The influence of natural products upon drug discovery.
D. Newman (2000)
Stereochemistry of the alkaloids codonopsine and codonopsinine
B. Tashkhodzhaev (2005)
Antidiabetic agents from medicinal plants.
M. Jung (2006)
Structural establishment of polygalatenosides A and B by total synthesis
C. Huang (2008)
More Efficient Palladium Catalyst for Hydrogenolysis of Benzyl Groups
Y. Li (2006)
Probing the aglycon binding site of a beta-glucosidase: a collection of C-1-modified 2,5-dideoxy-2,5-imino-D-mannitol derivatives and their structure-activity relationships as competitive inhibitors.
T. Wrodnigg (2004)
Two new pyrrolidine alkaloids, radicamines A and B, as inhibitors of alpha-glucosidase from Lobelia chinensis Lour.
M. Shibano (2001)
Stereochemical revision and absolute configuration of codonopsinine
H. Iida (1986)
Traceless sulfone linker cleavage triggered by ozonolysis: solid-phase synthesis of diverse α-β-unsaturated carbonyl compounds
Yi-Fan Chang (2008)
Straightforward Synthesis of Enantiopure 2-Aminomethyl and 2-Hydroxymethyl Pyrrolidines with Complete Stereocontrol
M. Marradi (2005)
The combinatorial synthesis of bicyclic privileged structures or privileged substructures.
D. A. Horton (2003)
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Pyrrolidine alkaloids and their promises in pharmacotherapy
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Synthesis and fucosidase inhibitory study of unnatural pyrrolidine alkaloid 4-epi-(+)-codonopsinine.
A. Kotland (2011)
General synthesis of sugar-derived azepane nitrones: precursors of azepane iminosugars.
Wen-Bo Zhao (2013)
Parallel synthesis of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids
Yi-Fan Chang (2010)
Copper(I)‐Catalyzed One‐Pot Synthesis of Highly Functionalized Pyrrolidines from Sulfonyl Azides, Alkynes, and Dimethyl 2‐(Phenylamino)maleate
D. Ramanathan (2015)
Synthesis of iminosugars via 1,3-dipolar cycloaddition reactions of nitrones to α,β-unsaturated sugar aldonolactones
S. Stecko (2011)
DDQ-Promoted Benzylic/Allylic sp(3) C-H Activation for the Stereoselective Intramolecular C-N Bond Formation: Applications to the Total Synthesis of (-)-Codonopsinine, (+)-5-epi-Codonopsinine, (+)-Radicamine B, and (-)-Codonopsinol.
M. Lingamurthy (2016)
Straightforward Synthesis of Diverse 1-Deoxyazapyranosides via Stereocontrolled Nucleophilic Additions to Six-Membered Cyclic Nitrones
Ting-Hao Chan (2010)
A concise and divergent approach to radicamine B and hyacinthacine A(3) based on a step-economic transformation
Jin-Cheng Liao (2012)
Unexpected regiochemistry in [3+2] cycloaddition reaction of azomethine ylides of indenoquinoxalinone series to arylidene malononitriles
A. Barkov (2018)
Novel 2-aryl-3;4;5-trihydroxypiperidines: Synthesis and glycosidase inhibition
H Zhao (2013)
Total synthesis of (−)-codonopsinol and (+)-2-epi codonopsinol via acid catalyzed amido cyclisation
Y. Jagadeesh (2010)
Stereoselective Synthesis of Trifluoromethyl Analogues of Polyhydroxypyrrolidines
Rama Kanwar Khangarot (2013)
Synthesis and anti-inflammatory activity of isoquebecol.
S. Cardinal (2017)
Stereoselective nucleophilic addition of PhSCF2 SiMe3 to chiral cyclic nitrones: asymmetric synthesis of gem-difluoromethylenated polyhydroxypyrrolizidines and -indolizidines.
Korkit Korvorapun (2015)
Metal-free, one-pot conversion of proline derivatives into 2-aryl-3-iodo pyrrolidines by a sequential scission-iodination-arylation process.
Venkateswara Rao Batchu (2014)
Iminoxyl radical-promoted dichotomous cyclizations: efficient oxyoximation and aminooximation of alkenes.
Xie-Xue Peng (2014)
Total synthesis of pyrrolidine alkaloid, Radicamine-B via Stille coupling
P. Mallesham (2011)
Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases
M. Bella (2018)
Re-exploring promising α-glucosidase inhibitors for potential development into oral anti-diabetic drugs: Finding needle in the haystack.
U. Ghani (2015)
Design and divergent synthesis of aza nucleosides from a chiral imino sugar.
Saúl Martínez-Montero (2012)
One-Pot Conversion of Proline Derivatives into Iodinated Iminosugar-Based Nucleosides, Useful Precursors of Highly Functionalized Nucleoside Analogues
A. Boto (2010)
Stereoselective synthesis of (+)-radicamine B
G. Shankaraiah (2011)
Chemo-enzymatic synthesis and glycosidase inhibitory properties of DAB and LAB derivatives.
Alda Lisa Concia (2013)
A Stereoselective Route to Aza-C-aryl Glycosides from Arynes and Chiral Nitrones
Rama Kanwar Khangarot (2012)
One-Pot Synthesis of Azanucleosides from Proline Derivatives -Stereoselectivity in Sequential Processes
A. Boto (2010)
An Efficient Synthesis of Aldohexose-Derived Piperidine Nitrones: Precursors of Piperidine Iminosugars
H Zhao (2013)
Thiyl radical-mediated cyclization of ω-alkynyl O-tert-butyldiphenylsilyloximes.
N. Shibata (2017)
Synthesis of fully substituted polyhydroxylated pyrrolizidines via Cope-House cyclization.
W. Zhang (2011)
Bioactive constituents from toxic seed plants in China
Jing Qu (2013)
Preparation of Pyranose‐Based Thioimidate N‐Oxides (TINOs)
S. Marques (2015)
Search of antimycobacterial activities in hybrid molecules with benzopyran skeleton
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