Application of electronic circular dichroism in configurational and conformational analysis of organic compounds

Berova, Nina; Bari, Lorenzo Di; Pescitelli, Gennaro

doi:10.1039/b515476f

Cited by 1,074 publications

(816 citation statements)

References 42 publications

(54 reference statements)

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“…4). Considering the exciton chirality rule, 36 the left-handed orientation of the ligand molecules predicts a longer-wavelength negative and a shorterwavelength positive CD band pair which is in full accordance with the measured spectroscopic data.…”

Section: Hsa Binding Studies By Affinity Chromatographysupporting

confidence: 85%

Synthesis and serum protein binding of novel ring-substituted harmine derivatives

et al. 2015

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A series of new derivatives of the natural β-carboline alkaloid harmine, introducing hydrophobic substituents into positions 7 and 9 were synthetized as potential anticancer agents. Their binding affinities for human serum albumin (HSA) and α 1 -acid-glycoprotein (AAG) were investigated by affinity chromatography combined with fluorescence, circular dichroism (CD) and UV absorption spectroscopy. The weak binding of harmine to both proteins (K a ~ 3 × 10 4 M -1 ) was highly increased by aromatic substitutions (K a ~ 10 5 -10 6 M -1 ).Derivatives having a substituted benzyl group in the N 9 -position of the β-carboline nucleus showed about tenfold and hundred fold affinity enhancement for HSA and AAG, respectively.Such a strong plasma protein interaction would be of pharmacokinetic relevance for these potential drug candidates. Induced CD spectra indicated the variant selective, dimeric binding of the 7-pyridylethoxy derivative to AAG. Absorbance and fluorescence spectra refer to the binding preference of the neutral form of the studied β-carbolines for both proteins.

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“…The absolute stereochemistry of compound 1 was determined by comparison of its electronic circular dichroism (ECD) spectrum with a spectrum computed for the rigid carbon skeleton of the P1 diastereomer (38). We examined the robustness of this method with four rigid monoterpenes, with excellent matches for (−) and (+)-borneol, camphene, limonene, and α-pinene (Dataset S4).…”

Section: Resultsmentioning

confidence: 99%

Computational-guided discovery and characterization of a sesquiterpene synthase from Streptomyces clavuligerus

Chow

Tian

Ramamoorthy

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Terpenoids are a large structurally diverse group of natural products with an array of functions in their hosts. The large amount of genomic information from recent sequencing efforts provides opportunities and challenges for the functional assignment of terpene synthases that construct the carbon skeletons of these compounds. Inferring function from the sequence and/or structure of these enzymes is not trivial because of the large number of possible reaction channels and products. We tackle this problem by developing an algorithm to enumerate possible carbocations derived from the farnesyl cation, the first reactive intermediate of the substrate, and evaluating their steric and electrostatic compatibility with the active site. The homology model of a putative pentalenene synthase (Uniprot: B5GLM7) from Streptomyces clavuligerus was used in an automated computational workflow for product prediction. Surprisingly, the workflow predicted a linear triquinane scaffold as the top product skeleton for B5GLM7. Biochemical characterization of B5GLM7 reveals the major product as (5S,7S,10R,11S)-cucumene, a sesquiterpene with a linear triquinane scaffold. To our knowledge, this is the first documentation of a terpene synthase involved in the synthesis of a linear triquinane. The success of our prediction for B5GLM7 suggests that this approach can be used to facilitate the functional assignment of novel terpene synthases.T erpenoid compounds form a large group of natural products synthesized by many species of plants, fungi, and bacteria. To date, more than 70,000 of these compounds have been identified, comprising ∼25% of all of the known natural products (Dictionary of Natural Products database, dnp.chemnetbase.com/intro/ index.jsp). Terpenoids and molecules containing terpenoid fragments are produced from two basic five-carbon building blocks: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) (1, 2). IPP and DMAPP are then converted into a series of terpenoid diphosphate esters of increasing chain lengths by chain length selective polyprenyl diphosphate synthases to give geranyl diphosphate (GPP, C 10 ), farnesyl diphosphate (FPP, C 15 ), geranylgeranyl diphosphate (GGPP, C 20 ), and higher five-carbon homologs (3). These molecules are substrates for terpene synthases, which catalyze hydroxylation, elimination, cyclization, and rearrangement reactions to produce much of the structural diversity of terpenoid molecules found in nature (4, 5).The two main classes of terpene synthases (class I and class II) are distinguished from one another by the mechanisms they use to initiate carbocationic cyclization and rearrangement reactions and by their respective folds (6, 7). Class I terpene synthases use active site Mg 2+ ions to bind and activate the diphosphate moieties of their substrates as leaving groups to generate highly reactive allylic carbocations. In those terpene synthases that catalyze cyclization reactions, the carbocations alkylate distal double bonds in the hydrocarbon chain. The initial cycliza...

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“…3) suggested the absolute configuration to be 1R, 2R, 3S, 6S, 7S, 8R, 9S, 10R, and 11R, which could also be supported by the exciton chirality method. 16 Compound 1 possesses a perhydroazulene ring system, and it looks like a cage due to the presence of c-lactone. Although pachydictyol and dictyol derivatives from the marine brown algae have a carbon skeleton similar to that of 1, 17,18 the positions attached by side chains and methyl groups are quite different.…”

mentioning

confidence: 99%

Citrinovirin with a new norditerpene skeleton from the marine algicolous fungus Trichoderma citrinoviride

Liang

Miao

Song

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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a b s t r a c tCitrinovirin (1), a novel norditerpene with an unprecedented carbon skeleton along with three known compounds, cyclonerodiol (2), 3-(2-hydroxypropyl)-4-(hexa-2E,4E-dien-6-yl)furan-2(5H)-one (3), and 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (4), was isolated from the culture of a marine brown alga-endophytic strain (cf-27) of Trichoderma citrinoviride. The structure and relative configuration of 1 were identified by spectroscopic methods, including 1D/2D NMR and MS. Its absolute configuration was established by analysis of ECD spectrum, aided by quantum chemical calculations. A plausible biogenetic pathway is proposed for 1, and it was evaluated to be active against Staphylococcus aureus.Ó 2016 Elsevier Ltd. All rights reserved.Marine-derived fungi have attracted a great attention for natural product researchers since the end of the last century, which afforded a series of candidates for the developments of new drugs and functional agents. 1 Marine alga-derived fungi made up a large group of them, and they were even the main contributors of new compounds of marine fungal origin. 2 More than 360 new compounds, involving polyketides, terpenoids, polyketide-terpenoids, peptides, alkaloids, and shikimate derivatives, were produced by marine algicolous fungi. 3,4 Especially, the structures featuring novel or rare scaffolds were often encountered in them, represented by varioxepine A, 5 aspeverin, 6 harzianone, 7 aspewentins A and B. 8 During our continuing investigation towards the structurally unique and biologically active metabolites from marine algicolous fungi, a brown alga-endophytic strain (cf-27) of Trichoderma citrinoviride was chemically examined. As a result, a novel norditerpene, citrinovirin (1), with an unprecedented skeleton along with three known compounds, including cyclonerodiol (2), 9 3-(2-hydroxypropyl)-4-(hexa-2E,4E-dien-6-yl)furan-2(5H)-one (3), 10 and 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (4), 11 was isolated and identified (Fig. 1). Herein, the isolation, structure elucidation, bioactivity evaluation, and plausible biogenetic pathway of compound 1 are described.Compound 1 (Table 1) of compound 1 showed one methyl singlet, two methyl doublets, one methyl triplet, two doublets of double doublets attributable to two oxygenated methines, one doublet of double doublets and one double doublet ascribable to two olefinic protons, and two doublets assignable two exchangeable protons. According to MS data, the exchangeable protons should be derived from two hydroxy groups. The 13 C NMR spectrum (Table 1) along with DEPT and HSQC data demonstrated the presence of four methyls, three methylenes, ten methines, and two nonprotonated carbons. Based on 1 H

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“…Four typical situations are encountered [83]. A chiral guest and an achiral chromophoric host compound such as a calixarene or a bisporphyrin can form a complex that exhibits an induced CD within the absorption bands of the host.…”

Section: Electronic Optical Activitymentioning

confidence: 99%

“…Attempts to theoretically simulate observed UV-visible CD spectra focus on quantum-chemical calculations of the rotational strength (1.2) for the corresponding electronic transitions [81,82]. At present, their use remains significantly limited by the molecular size, conformational flexibility, and difficulties in obtaining sufficiently accurate and reliable descriptions of the corresponding excited electronic states [81][82][83]. CD is immensely useful in nanoscience, but mainly in its qualitative aspects for monitoring conformation changes, especially inversion of chirality via reversal of CD signals.…”

Section: Electronic Optical Activitymentioning

confidence: 99%

An Introduction to Chirality at the Nanoscale

Barron

Chirality at the Nanoscale

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Application of electronic circular dichroism in configurational and conformational analysis of organic compounds

Cited by 1,074 publications

References 42 publications

Synthesis and serum protein binding of novel ring-substituted harmine derivatives

Computational-guided discovery and characterization of a sesquiterpene synthase from Streptomyces clavuligerus

Citrinovirin with a new norditerpene skeleton from the marine algicolous fungus Trichoderma citrinoviride

An Introduction to Chirality at the Nanoscale

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