scholarly journals Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpen Aminodiols

2019 ◽  
Vol 21 (1) ◽  
pp. 184
Author(s):  
Dániel Ozsvár ◽  
Viktória Nagy ◽  
István Zupkó ◽  
Zsolt Szakonyi
Keyword(s):  
Antiproliferative Activity ◽  
Ring Opening ◽  
Stereoselective Synthesis ◽  
Click Reaction ◽  
Substituent Effects ◽  
Ring Closure ◽  
Secondary Amines ◽  
Structure Activity ◽  
Cis And Trans ◽  
Benzyl Substituent

A library of steviol-based trifunctional chiral ligands was developed from commercially available natural stevisoide and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The key intermediate steviol methyl ester was prepared according to literature procedure. Depending on the epoxidation process, both cis- and trans-epoxyalcohols were obtained. Subsequent oxirane ring opening with primary and secondary amines afforded 3-amino-1,2-diols. The ring opening with sodium azide followed by a “click” reaction with alkynes resulted in dihydroxytriazoles. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. The resulting steviol-type aminodiols were tested against a panel of human adherent cancer cell lines (A2780, SiHa, HeLa, and MDA-MB-231). It was consistently found that the N-benzyl substituent is an essential part within the molecule and the ring closure towards N-benzyl substituted oxazolidine ring system increased the antiproliferative activity to a level comparable with that of cisplatine. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol systems.

scholarly journals Stereoselective Synthesis and Investigation of Isopulegol-Based Chiral Ligands

2019 ◽  
Vol 20 (16) ◽  
pp. 4050 ◽  
Author(s):  
Tam Minh Le ◽  
Tamás Szilasi ◽  
Bettina Volford ◽  
András Szekeres ◽  
Ferenc Fülöp ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Ring Opening ◽  
Stereoselective Synthesis ◽  
Substituent Effects ◽  
Ring Closure ◽  
Chiral Ligands ◽  
Primary Amines ◽  
Structure Activity ◽  
Stereoselective Reactions ◽  
Stereoselective Epoxidation

A library of isopulegol-based bi-, tri- and tetrafunctional chiral ligands has been developed from commercially available (−)-isopulegol and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. Michael addition of primary amines towards α-methylene-γ-butyrolactone, followed by reduction, was accomplished to provide aminodiols in highly stereoselective transformations. Stereoselective epoxidation of (+)-neoisopulegol, derived from natural (−)-isopulegol, and subsequent oxirane ring opening with primary amines afforded aminodiols. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. Hydroxylation of (+)-neoisopulegol resulted in diol, which was then transformed into aminotriols by aminolysis of its epoxides. Dihydroxylation of (+)-neoisopulegol or derivatives with OsO4/NMO gave neoisopulegol-based di-, tri- and tetraols in highly stereoselective reactions. The antimicrobial activity of aminodiol and aminotriol derivatives as well as di-, tri- and tetraols was also explored. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol and aminotriol systems.

scholarly journals Synthesis and Transformation of (-)-Isopulegol-Based Chiral β-Aminolactones and β-Aminoamides

2018 ◽  
Vol 19 (11) ◽  
pp. 3522 ◽  
Author(s):  
Tam Le ◽  
Péter Bérdi ◽  
István Zupkó ◽  
Ferenc Fülöp ◽  
Zsolt Szakonyi
Keyword(s):  
Ring Opening ◽  
Lactone Ring ◽  
Substituent Effects ◽  
Ring System ◽  
Secondary Amines ◽  
Amino Acid Derivatives ◽  
Structure Activity ◽  
Primary And Secondary Amines ◽  
Stereoselective Reactions ◽  
Antiproliferative Activities

A library of isopulegol-based β-amino acid derivatives has been developed from commercially-available (-)-isopulegol. Michael addition of primary and secondary amines towards α,β-unsaturated γ-lactones was accomplished resulting in β-aminolactones in highly-stereoselective reactions. Ring-opening of β-aminolactones with different amines furnished excellent yields of β-aminoamides. Moreover, the applicability of aminolactones in peptide synthesis was examined by opening the lactone ring with α- and β-aminoesters, providing dipeptides as promising chiral substrates for the synthesis of foldamers. The antiproliferative activities of β-aminolactones and β-aminoamides were explored, and the structure-activity relationships were studied from the aspects of the stereochemistry of the monoterpene ring and the substituent effects on the β-aminoamide ring system. The N-unsubstituted (-)-isopulegol-based β-aminoamides exhibited considerable antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF7 and MDA-MB-231).

A Stereochemical and Kinetic Study of the Conversion of Methyl Cyclopropyl Ketones to 4,5-Dihydrofurans

1973 ◽  
Vol 51 (10) ◽  
pp. 1487-1493 ◽  
Author(s):  
Donald Edward McGreer ◽  
James William McKinley
Keyword(s):  
Kinetic Study ◽  
Ring Opening ◽  
Photochemical Reactions ◽  
Order Reaction ◽  
Ring Closure ◽  
Hydrogen Shift ◽  
First Order ◽  
Bond Rotation ◽  
Cyclopropyl Ketones ◽  
Cis And Trans

The thermal and photochemical conversion of (1R*,2R*,3S*), (1S*,2R*,3S*), and (1S*,2R*,3R*)-1-acetyl-1,2-dimethyl-3-phenylcyclopropane (1, 2, and 3) to cis- and trans-2,3,4-trimethyl-5-phenyl-4,5-dihydrofurans has been studied. Concurrent with this reaction is an equilibration of 1, 2, and 3, a thermal ring opening of 1 by a 1,5-hydrogen shift, and a cyclopropane-to-propene type reaction under the photochemical conditions. The dihydrofuran from 1 and 2 by the thermal and photochemical conditions is 97% trans- and 3% cis- corresponding to predominant retention at the migrating carbon. The dihydrofuran formed from 3 by the thermal and photochemical reaction is 85% cis- and 15% trans- again corresponding to predominant retention. A kinetic study of the rearrangement of 1-acetyl-1-methyl-2-phenylcyclopropane to 1,2-dimethyl-5-phenyl-4,5-dihydrofuran provides Ea of 48.1 kcal/mol and log A of 14.9 for this first order reaction in the temperature range of 255–288 °C.It is concluded that the thermal and photochemical reactions occur by a non-concerted process through a common 1,3-diradical intermediate in which bond rotation and ring closure steps are competitive.

scholarly journals Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes

Catalysts ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 474
Author(s):  
Mounir Raji ◽  
Tam Minh Le ◽  
Ferenc Fülöp ◽  
Zsolt Szakonyi
Keyword(s):  
Molecular Modeling ◽  
Ring Opening ◽  
Benzyl Bromide ◽  
Allylic Alcohol ◽  
Ring Closure ◽  
Reaction Pathways ◽  
Secondary Amines ◽  
Tridentate Ligands ◽  
Stereoselective Epoxidation ◽  
Carbonyl Function

A library of pinane-based chiral aminodiols, derived from natural (−)-β-pinene, were prepared and applied as chiral catalysts in the addition of diethylzinc to aldehydes. (−)-β-Pinene was reacted to provide 3-methylenenopinone, followed by a reduction of the carbonyl function to give a key allylic alcohol intermediate. Stereoselective epoxidation of the latter and subsequent ring opening of the resulting oxirane with primary and secondary amines afforded aminodiols. The regioselectivity of the ring closure of the N-substituted secondary aminodiols with formaldehyde was examined and exclusive formation of oxazolidines was observed. Treatment of the allylic alcohol with benzyl bromide provided the corresponding O-benzyl derivative, which was transformed into O-benzyl aminodiols by aminolysis. Ring closure of the N-isopropyl aminodiol derivative with formaldehyde resulted in spirooxazolidine. The obtained potential catalysts were applied in the reaction of both aromatic and aliphatic aldehydes to diethylzinc providing moderate to good enantioselectivities (up to 87% ee). Through the use of molecular modeling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modeling at the RHF/LANL2DZ level of theory was successfully applied for interpretation of the stereochemical outcome of the reactions leading to display excellent (R) enantioselectivity in the examined transformation.

Trypanocidal Structure-Activity Relationshipfor Cis- and Trans-methylpluviatolide

Planta Medica ◽  
2008 ◽  
Vol 74 (03) ◽  
Author(s):  
R Silva ◽  
J Saraiva ◽  
S Albuquerque ◽  
C Curti ◽  
PM Donate ◽  
...  
Keyword(s):  
Structure Activity ◽  
Cis And Trans

Microwave-assisted Synthesis of Polymethoxychalcone Mannich Bases and Their Antiproliferative Activity

2019 ◽  
Vol 16 (2) ◽  
pp. 117-121 ◽  
Author(s):  
Peipei Han ◽  
Wenhua Zhou ◽  
Mingxia Chen ◽  
Qiuan Wang
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Mannich Base ◽  
Cancer Cell Lines ◽  
Secondary Amines ◽  
Conventional Heating ◽  
Microwave Assisted ◽  
Ic50 Values ◽  
Antiproliferative Activities

A series of eight polymethoxychalcone Mannich base derivatives 2a-2h was synthesized via the microwave-assisted Mannich reaction of natural product 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1) with various secondary amines and formaldehyde. Compared to conventional heating method (80°C), the microwave-assisted method (700W, 65°C) is efficient with short reaction time (0.5-1 h) and good yields (74-88%). The antiproliferative activities of eight Mannich base derivatives were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) by CCK-8 assay. The results showed that all of the Mannich base derivatives exhibited potential antiproliferative activities on tested cancer cell lines with the IC50 values of 9.13-48.51 µM. Some active compounds exhibited more activity as compared to positive control cis-Platin. Among them, compound 2b revealed to have the strongest antiproliferative activity against all the three cancer cell lines with IC50 values ranging from 9.13 to 11.24 µM.

Substituent Effects in Mechanochemical Allowed and Forbidden Cyclobutene Ring-Opening Reactions

2021 ◽  
Author(s):  
Cameron L. Brown ◽  
Brandon H. Bowser ◽  
Jan Meisner ◽  
Tatiana B. Kouznetsova ◽  
Stefan Seritan ◽  
...  
Keyword(s):  
Ring Opening ◽  
Substituent Effects ◽  
Ring Opening Reactions

scholarly journals Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1380
Author(s):  
Xiutao Wu ◽  
Lijie Gong ◽  
Chen Chen ◽  
Ye Tao ◽  
Wuxi Zhou ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Normal Cell ◽  
Selectivity Index ◽  
Cytotoxic Activities ◽  
Structure Activity ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Hct 116 ◽  
Systematic Structure

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.

scholarly journals Stereoselective Synthesis of Tetraalkyl Cyclobutene-1,2,3,4-tetracarboxylates. Synthesis of Tetraalkyl (Z,Z)-Buta-1,3-diene-1,2,3,4-tetracarboxylates

1999 ◽  
Vol 23 (8) ◽  
pp. 512-513
Author(s):  
Issa Yavari ◽  
Farahnaz Nourmohammadian
Keyword(s):  
Ring Opening ◽  
Wittig Reaction ◽  
Stereoselective Synthesis ◽  
Intramolecular Wittig Reaction ◽  
Ring Opening Reactions ◽  
Boiling Toluene

Tetraalkyl cyclobutene-1,2,3,4-tetracarboxylates, prepared by intramolecular Wittig reaction between a vinylphosphonium salt and diethyl 2-oxobutanedioate, undergo electrocyclic ring-opening reactions, in boiling toluene, to produce highly electron-deficient 1,3-dienes.

Sign in / Sign up

Export Citation Format

Share Document