Synthesis and Structural Determination of New Brassinosteroid 24-Nor-5α-Cholane Type Analogs

Natural brassinosteroids possess a 22R, 23R configuration that appears essential for biological activity. It is, therefore, interesting to elucidate if the activity of brassinosteroids with a short side chain depends on the C22 configuration. Herein, we describe the synthesis of new brassinosteroids analogs with 24-norcholane type of side chain and R configuration at C22. The initial reaction is the dihydroxylation of a terminal olefin that leads to S/R epimers. Three different methods were tested in order to evaluate the obtained S/R ratio and the reaction yields. The results indicate that Upjohn dihydroxylation is the most selective reaction giving a 1.0:0.24 S/R ratio, whereas a Sharpless reaction leads to a mixture of 1.0:0.90 S/R with 95% yield. Using the latter mixture and following a previous reported method, benzoylated derivatives and both S and R brassinosteroids analogs were synthesized. All synthesized compounds were completely characterized by NMR spectroscopy, and HRMS of new compounds are also given. In conclusion, a synthetic route for preparation of new analogs of brassinosteroids of 24-norcholane type and R configuration at C22 were described. It is expected that this will help to elucidate if a configuration at C22 is a structural requirement for hormonal growth activity in plants.

Download Full-text

Polypeptides Folding: Rules for the Calculation of the Backbone Dihedral Angles φ starting from the Amino Acid Sequence

10.26434/chemrxiv.12000132 ◽

2020 ◽

Author(s):

Michele Larocca

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Theoretical Approach ◽

Polypeptide Chain ◽

Hydrophobic Effect ◽

Side Chain ◽

Dihedral Angles ◽

Mechanical Forces ◽

Specific Chemical

<p>Protein folding is strictly related to the determination of the backbone dihedral angles and depends on the information contained in the amino acid sequence as well as on the hydrophobic effect. To date, the type of information embedded in the amino acid sequence has not yet been revealed. The present study deals with these problematics and aims to furnish a possible explanation of the information contained in the amino acid sequence, showing and reporting rules to calculate the backbone dihedral angles φ. The study is based on the development of mechanical forces once specific chemical interactions are established among the side chain of the residues in a polypeptide chain. It aims to furnish a theoretical approach to predict backbone dihedral angles which, in the future, may be applied to computational developments focused on the prediction of polypeptide structures.</p>

Download Full-text

Synthesis and Biological Activity of Brassinosteroid Analogues with a Nitrogen-Containing Side Chain

International Journal of Molecular Sciences ◽

10.3390/ijms22010155 ◽

2020 ◽

Vol 22 (1) ◽

pp. 155

Author(s):

Mikhail V. Diachkov ◽

Karoll Ferrer ◽

Jana Oklestkova ◽

Lucie Rarova ◽

Vaclav Bazgier ◽

...

Keyword(s):

Biological Activity ◽

Functional Groups ◽

Side Chain ◽

Biotic And Abiotic Stresses ◽

Short Side ◽

Arabidopsis Root ◽

Physiological Processes ◽

Growth Promoting ◽

The Impact ◽

Brassinosteroid Analogues

Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.

Download Full-text

Determination of the side chain pKa values of the lysine residues in calmodulin.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)41546-3 ◽

1993 ◽

Vol 268 (30) ◽

pp. 22420-22428

Author(s):

M Zhang ◽

H.J. Vogel

Keyword(s):

Side Chain ◽

Pka Values ◽

Lysine Residues

Download Full-text

Composite short-side-chain PFSA electrolyte membranes containing selectively modified halloysite nanotubes (HNTs)

Journal of Materials Science ◽

10.1007/s10853-021-06109-4 ◽

2021 ◽

Author(s):

Sahng Hyuck Woo ◽

Aurélie Taguet ◽

Belkacem Otazaghine ◽

Alia Akrout ◽

Sara Cavaliere ◽

...

Keyword(s):

Halloysite Nanotubes ◽

Side Chain ◽

Short Side ◽

Electrolyte Membranes

Download Full-text

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

Molecules ◽

10.3390/molecules26040890 ◽

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.

Download Full-text

Reaktive E=C(p–p)π Systeme, XXXIV Addition von Alkoholen oder primären Aminen an Phosphaalkene F3CP=C(F)OR. Neue Trifluormethylphosphane und -phosphaalkene/Reactive E = C( p – p ) π-Systems, XXXIV Addition of Alcohols or Primary Amines to Phosphaalkenes F3CP= C(F)OR . Novel Trifluoromethylphosphanes and Phosphaalkenes

Zeitschrift für Naturforschung B ◽

10.1515/znb-1993-0114 ◽

1993 ◽

Vol 48 (1) ◽

pp. 58-67 ◽

Cited By ~ 10

Author(s):

Joseph Grobe ◽

Duc Le Van ◽

Gudrun Lange

Keyword(s):

High Resolution Mass Spectrometry ◽

Molar Ratio ◽

Primary Amines ◽

The Novel ◽

Experimental Conditions ◽

Pull System ◽

Fragment Ions ◽

New Compounds ◽

C Nmr

The course of the reactions o f fluorophosphaalkenes F3CP = C (F)OR [R = Me (1), Et (2)] with methanol or ethanol strongly depends on the experimental conditions. Thus at 70 °C a mixture of the 2-phosphapropionic acid ester F3CP (H )CO2R [R = Me (3), Et (4)] and trifluoromethylphosphane H2PCF3 is formed [molar ratio: 3 or 4 /H2 CF3 ≈1/1]. If the precursors F3CP (H )CO2R [R = Me (3), Et) are used as starting materials, the reaction with ROH under the same conditions affords 3 and 4, respectively, (90 to 95% yield) with only traces of H2PCF 3. In the presence o f iPr2NH these precursors react with R′OH to give the novel trifluoromethylphosphaalkenes F3CP = C (OR )OR [R /R′: Me/Me (6); E t/E t (7); Me/Et (8)]. With Et2NH , 3 undergoes an addition/elimination process yielding the interesting push/pull system Et2N(F)C = P-CO2Me (5). 1 and 2 react with primary amines R′NH2 (R′= tBu, Me) with stereoselective formation of the fairly labile phosphaalkenes F3CP = C(OR)NHR′ [R /R′: Me/tBu (9), Et/tBu(10), Me/Me (11)] with trans-positions for CF3 and NHR′.The new compounds 3 -11 were characterized by spectroscopic investigations (1H , 19F, 31P, 13C NMR ; IR, MS) and determination of M+ or typical fragment ions [M+ -OR ] by high resolution mass spectrometry.

Download Full-text

Two lithium tricyanomethanide compounds: syntheses and single-crystal structure determination of LiK[C(CN)3]2 and Li[C(CN)3]·½ (H3C)2CO

Zeitschrift für Naturforschung B ◽

10.1515/znb-2014-0250 ◽

2015 ◽

Vol 70 (3) ◽

pp. 191-196 ◽

Cited By ~ 1

Author(s):

Olaf Reckeweg ◽

Francis J. DiSalvo

Keyword(s):

Crystal Structure ◽

Single Crystal ◽

Single Crystals ◽

Structure Determination ◽

Monoclinic Space Group ◽

Orthorhombic Space Group ◽

Space Group ◽

Cell Parameters ◽

New Compounds

AbstractThe new compounds LiK[C(CN)3]2 and Li[C(CN)3]·½ (H3C)2CO were synthesized and their crystal structures were determined. Li[C(CN)3]·½ (H3C)2CO crystallizes in the orthorhombic space group Ima2 (no. 46) with the cell parameters a=794.97(14), b=1165.1(2) and c=1485.4(3) pm, while LiK[C(CN)3]2 adopts the monoclinic space group P21/c (no. 14) with the cell parameters a=1265.7(2), b=1068.0(2) and c=778.36(12) pm and the angle β=95.775(7)°. Single crystals of K[C(CN)3] were also acquired, and the crystal structure was refined more precisely than before corroborating earlier results.

Download Full-text

Gating Competence of Constitutively Open CLC-0 Mutants Revealed by the Interaction with a Small Organic Inhibitor

The Journal of General Physiology ◽

10.1085/jgp.200308784 ◽

2003 ◽

Vol 122 (3) ◽

pp. 295-306 ◽

Cited By ~ 52

Author(s):

Sonia Traverso ◽

Laura Elia ◽

Michael Pusch

Keyword(s):

Chloride Channels ◽

Bound State ◽

Side Chain ◽

Pore Channel ◽

Kinetic Properties ◽

Wild Type ◽

High Affinity ◽

Critical Residue ◽

Fast Gating

Opening of CLC chloride channels is coupled to the translocation of the permeant anion. From the recent structure determination of bacterial CLC proteins in the closed and open configuration, a glutamate residue was hypothesized to form part of the Cl−-sensitive gate. The negatively charged side-chain of the glutamate was suggested to occlude the permeation pathway in the closed state, while opening of a single protopore of the double-pore channel would reflect mainly a movement of this side-chain toward the extracellular pore vestibule, with little rearrangement of the rest of the channel. Here we show that mutating this critical residue (Glu166) in the prototype Torpedo CLC-0 to alanine, serine, or lysine leads to constitutively open channels, whereas a mutation to aspartate strongly slowed down opening. Furthermore, we investigated the interaction of the small organic channel blocker p-chlorophenoxy-acetic acid (CPA) with the mutants E166A and E166S. Both mutants were strongly inhibited by CPA at negative voltages with a >200-fold larger affinity than for wild-type CLC-0 (apparent KD at −140 mV ∼4 μM). A three-state linear model with an open state, a low-affinity and a high-affinity CPA-bound state can quantitatively describe steady-state and kinetic properties of the CPA block. The parameters of the model and additional mutagenesis suggest that the high-affinity CPA-bound state is similar to the closed configuration of the protopore gate of wild-type CLC-0. In the E166A mutant the glutamate side chain that occludes the permeation pathway is absent. Thus, if gating consists only in movement of this side-chain the mutant E166A should not be able to assume a closed conformation. It may thus be that fast gating in CLC-0 is more complex than anticipated from the bacterial structures.

Download Full-text