Convergent Synthesis of &lt;i&gt;trans&lt;/i&gt;-2,6-Disubstituted Piperidine Alkaloid, (−)-&lt;i&gt;iso&lt;/i&gt;-6-Spectaline by Palladium-Catalyzed Cyclization

Kameda, Risako; Sohma, Takuto; Kobayashi, Kazuya; Uchiyama, Ryosuke; Nosaka, Kazuto; Konno, Hiroyuki; Akaji, Kenichi; Hattori, Yoshiyuki

doi:10.1248/cpb.c18-00817

Cited by 3 publications

(1 citation statement)

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“…Therefore, only three compounds (the two alkaloids spectaline (1) and iso-6-cassine (2) and sitosterol 3-O-β-D-glucopyranoside (6)) isolated from fraction CSBc which was the most active fraction, inhibited the growth of some of the studied bacteria, but with weak activities. Indeed, (−)-iso-6-spectaline has been reported to exhibit a weak antimicrobial activity against Staphylococcus epidermidis [39]. Cassine isolated from Senna racemosa Mill.…”

Section: Discussionmentioning

confidence: 99%

Bark extract of Cassia sieberiana DC. (Caesalpiniaceae) displayed good antibacterial activity against MDR gram-negative phenotypes in the presence of phenylalanine-arginine β-naphthylamide

Ambadiang

Atontsa

Tankeo

et al. 2020

BMC Complement Med Ther

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Background Multidrug-resistant (MDR) bacteria remain a major cause of morbidity and mortality globally. The present study was designed to investigate the in vitro antibacterial activities of crude methanol extract and constituents isolated by Column Chromatography (CC) from Cassia sieberiana bark (CSB) against ten MDR Gram-negative bacteria, as well as the mechanisms of action of the most active sample. Methods The antibacterial activity of the tested samples (extract, the fractions and their compounds isolated by CC and the structures obtained by exploiting 1H and 13C Nuclear magnetic resonance (NMR) spectra) in the presence and absence of an efflux pumps inhibitor, phenylalanine-arginine β-naphthylamide (PAβN), was evaluated using the micro-dilution method. The effects of the most active sample were evaluated on the cell growth kinetic and on the bacterial H+-ATPase proton pumps. Results Phytochemical composition of the crude extract showed a rather selective distribution of secondary metabolites (presence of polyphenols, tannins, steroids, triterpenes, flavonoids, alkaloids, saponins and absence of anthocyanins, anthraquinones). The tested samples displayed different antibacterial activities with minimal inhibitory concentrations (MICs) ranging from 64 to 512 μg/mL. Crude extract (CS) and fraction CSc showed the highest inhibitory spectra, both inhibiting all of the studied bacteria except Enterobacter aerogenes EA27 strain. Fraction CSc exerted bactericidal effects on most bacteria meanwhile, crude extract (CS) and sub-fraction CSc2 exerted bacteriostatic effects. Compounds 1 (spectaline) and 2 (iso-6-cassine) inhibited the growth of 70% (Escherichia coli ATCC8739 and AG102, Klebsiella pneumoniae ATCC11296, Enterobacter aerogenes ATCC13048 and EA27, Providencia stuartii ATCC29916, Pseudomonas aeruginosa PA01) and 60% (Escherichia coli ATCC8739, Klebsiella pneumoniae ATCC11296 and KP55, Providencia stuartii ATCC29916, Pseudomonas aeruginosa PA01 and PA124) of bacteria respectively with MICs ranging from 128 to 512 μg/mL. In the presence of PAβN, the activities of crude extract CS, fraction CAc and sub-fraction CSc2 strongly increased on most bacteria strains as their MICs significantly decreased. Sub-fraction CSc2 inhibited the H+-ATPase proton pumps and altered growth kinetic of Escherichia coli ATCC8739. Conclusion The overall results justify the traditional use of C. sieberiana for the treatment of bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Bark extract of Cassia sieberiana DC. (Caesalpiniaceae) displayed good antibacterial activity against MDR gram-negative phenotypes in the presence of phenylalanine-arginine β-naphthylamide

Ambadiang

Atontsa

Tankeo

et al. 2020

BMC Complement Med Ther

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Stereoselective synthesis of 2,6-disubstituted piperidine alkaloids

Srivastava

Macha

2020

Org. Biomol. Chem.

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Studies on Functional Molecules Based on Peptide Chemistry

Akaji

2021

YAKUGAKU ZASSHI

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Studies on functional molecules starting from syntheses of cysteine-containing peptides and protein are described. Starting from evaluation of a cysteine speciˆc side-reaction, a speciˆc reaction for disulˆde-bond formation was developed. The reaction made it possible to independently construct a disulˆde bridge without eŠecting the existing disulˆde bonds, which resulted in a unique approach for the synthesis of human insulin by site-speciˆc disulˆde bond formation. In a series of studies on sulfur-containing amino acids, another cysteine related un-natural amino acid, a-methyl cysteine, was used for the total syntheses of natural products containing a unique thiazorine/thiazole ring system. Chloroimidazolidium coupling reagent developed by us was eŠective for the successive couplings of the a-methyl cysteine residues. Based on these synthetic studies, design and evaluation of protease inhibitors were then studied, since a stereo-speciˆc synthesis of the key structure is crucial to make the inhibitor an eŠective functional molecule in the interactions with its target protease. As the target proteases, b-site amyloid precursor protein cleaving enzyme 1 (BACE1) and chymotrypsin-like protease of severe acute respiratory syndrome (SARS 3CL protease) were selected: the former is a crucial enzyme for amyloid b production and the latter is an essential enzyme for the re-construction of SARS corona virus in host cells. Structure optimization procedure of the respective inhibitors are described based on X-ray crystal structure analyses of the inhibitor-protease complex.

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Convergent Synthesis of <i>trans</i>-2,6-Disubstituted Piperidine Alkaloid, (−)-<i>iso</i>-6-Spectaline by Palladium-Catalyzed Cyclization

Cited by 3 publications

References 18 publications

Bark extract of Cassia sieberiana DC. (Caesalpiniaceae) displayed good antibacterial activity against MDR gram-negative phenotypes in the presence of phenylalanine-arginine β-naphthylamide

Bark extract of Cassia sieberiana DC. (Caesalpiniaceae) displayed good antibacterial activity against MDR gram-negative phenotypes in the presence of phenylalanine-arginine β-naphthylamide

Stereoselective synthesis of 2,6-disubstituted piperidine alkaloids

Studies on Functional Molecules Based on Peptide Chemistry

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