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Isochroman and azole moieties are both present in a wide variety of biologically active molecules. Their efficient combination under mild reaction conditions is beneficial for obtaining small-molecule drug candidates. In this paper, we describe electrochemical α-C(sp3)–H/N–H cross-coupling reactions between isochromans and azoles, yielding products in moderate to excellent yields. This protocol does not require any catalysts or exogenous oxidants and can be performed at room temperature under air. Control experiments and cyclic voltammetry showed that the reaction may proceed through both radical coupling and nucleophilic addition processes.

Isochromans are valuable building blocks for the synthesis of natural products and bioactive compounds. Herein, we report a diastereoselective halo‐cycloacetalization of olefinic aldehydes and alcohols using N‐haloamides as the halogenating agents. The reaction conditions are mild and can be operated in the absence of external catalysts. Olefinic aldehydes bearing different substituents and various alcohols are compatible with the reaction protocol, giving isochroman derivatives efficiently. [ABSTRACT FROM AUTHOR]

Isochroman and azole moieties are both present in a wide variety of biologically active molecules. Their efficient combination under mild reaction conditions is beneficial for obtaining small-molecule drug candidates. In this paper, we describe electrochemical α-C(sp 3 )-H/N-H cross-coupling reactions between isochromans and azoles, yielding products in moderate to excellent yields. This protocol does not require any catalysts or exogenous oxidants and can be performed at room temperature under air. Control experiments and cyclic voltammetry showed that the reaction may proceed through both radical coupling and nucleophilic addition processes.

Abstract The optimization and modulation of the properties of photochromic compounds, such as their activation wavelengths and thermal relaxation half‐lives (τ1/2), are essential for their adaptation in various applications. In this work, we studied the effect of co‐planarization of the rotary fragment of two photochromic hydrazones with the core of the molecule on their switching properties. The Z and E isomers of both compounds exhibit red‐shifted absorption bands relative to their twisted versions, allowing for their photoswitching using longer wavelengths of light. Additionally, the thermal half‐lives of both hydrazones are drastically shortened from hundreds of years to days.

The optimization and modulation of the properties of photochromic compounds, such as their activation wavelengths and thermal relaxation half‐lives (τ1/2), are essential for their adaptation in various applications. In this work, we studied the effect of co‐planarization of the rotary fragment of two photochromic hydrazones with the core of the molecule on their switching properties. The Z and E isomers of both compounds exhibit red‐shifted absorption bands relative to their twisted versions, allowing for their photoswitching using longer wavelengths of light. Additionally, the thermal half‐lives of both hydrazones are drastically shortened from hundreds of years to days. [ABSTRACT FROM AUTHOR]

The way therapeutic compounds interact with serum protein provides valuable information on their pharmacokinetics, toxicity, effectiveness, and even their structural-related information. Isochroman (IC) is a phytochemical compound obtained from the leaves of Olea europea plant. The derivatives of IC have various pharmacological properties including antidepressants, antihistamines, antiinflammation, anticonvulsants, appetite depressants, etc. The binding of small molecules to bovine serum albumin (BSA) is useful to ensure their efficacy. Thus, in this study, we have found out the binding mode of IC with BSA using several spectroscopic and in silico studies. UV and fluorescence spectroscopy suggested the complex formation between IC and BSA with a binding constant of 10 3 M -1 . IC resulted in fluorescence quenching in BSA through static mechanism. The microenvironmental and conformational changes in BSA were confirmed using synchronous and three-dimensional studies. Site marker experiment revealed the IC binding in site-III of BSA. The influence of vitamins, metals and β-cyclodextrin (β-CD) on binding constant of IC-BSA complex was also examined. Circular dichroism spectra showed that α-helical of BSA decreased upon interaction with IC. Computational and experimental results were complimentary with one another and assisted in determining the binding sites, nature of bonds and amino acids included in the IC-BSA complex formation.Communicated by Ramaswamy H. Sarma.

Abstract Fe(OTf) 2 has been found to be an efficient catalyst for the Oxa-Pictet–Spengler cyclization reaction leading to isochromans. A series of substituted isochromans were obtained with good to excellent isolated yields by coupling β-arylethanols with aldehydes or ketals under the catalysis of 1 mol% of Fe(OTf) 2 at 70 °C. Using a cheap, less-toxic catalyst with water as the only byproduct, this iron-catalyzed Oxa-Pictet–Spengler reaction can be considered environmentally-friendly and atom-economic. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

This work extends the present knowledge about the ability of filamentous fungi and Baker’s Yeast to selectively transform oxygen-containing compounds. Previously, it has been demonstrated that several species of the Aspergillus genus are able to perform selective oxidation of benzopyrans. Isochroman or 3,4-dihydro-1 H -benzopyran ( 1 ) was chosen as model substrate for the biotransformation since related motifs are often found in the structure of natural products with important biological and pharmacological activities. All the tested strains showed the ability to oxidize 1 . Chemodivergent reaction pathways between the employed microorganisms were observed. The use of cytochrome P450 enzyme inhibitors, and different oxygenation conditions allowed to inquire about the type of enzymes involved in the process. The results obtained were compared with chemical one-electron oxidation of compound 1 and thus, a metabolic pathway was proposed. [ABSTRACT FROM AUTHOR]

Trimethylsilyl triflate (TMSOTf) can be efficiently used for the synthesis of isochromans via Pictet-Spengler type reaction of vinylogous esters in good yields. The methodology is applied for the formal synthesis of key intermediate alcohols for the synthesis of D4 antagonist sonepiprazole (±)-U-101387 and the isochroman (±)-U-54537. [ABSTRACT FROM AUTHOR]

Six new compounds, colletobredins A–D (1–4) and colletomelleins A and B (5 and 6), along with 12 previously identified compounds, were isolated from the culture broth of Colletotrichum aotearoa BCRC 09F0161, a fungal endophyte residing in the leaves of an endemic Formosan plant Bredia oldhamii Hook. f. (Melastomataceae). The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR-ESIMS and extensive 1D and 2D NMR techniques. The effects of some isolates on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated murine macrophage RAW264.7 cells were evaluated. All these compounds inhibited NO production in activated macrophages without any cytotoxicity at a concentration of 100 μM. Of these isolates, 1 showed weak NO inhibitory activity with IC50 value of 182.2 μM. To the best of our knowledge, this is the first report on isochroman glycoside metabolites (1–4) from the genus Colletotrichum. [ABSTRACT FROM AUTHOR]

A base-catalyzed ring-opening of 1-benzylisochromans 1 firstly produced 2-alkenylstilbenes 2, which then underwent a mild acid-catalyzed intramolecular cyclization to furnish 1,2-disubstituted indenes 3 in high yields. Subsequently, a base-catalyzed isomerization of the 1,2-disubstituted indenes 3 afforded the more stable 2,3-disubstituted indenes 4 in almost quantitative yields. [ABSTRACT FROM AUTHOR]

Hydroxytyrosol (HT) and a set of synthetic isochroman derivatives of HT have been studied with regards to their radical scavenging activity in the gas employing density functional theory (DFT) and the Becke's 3 Lee Yang Parr (B3LYP) functional. Values of molecular descriptors (bond dissociation enthalpy, BDE; ionization potential, IP; proton dissociation enthalpy, PDE; proton affinity, PA; electron transfer energy, ETE; electron accepting power, ɷ +; electron donating power, ɷ −; net electrophilicity, Δɷ ± ) characterizing the hydrogen atom or electron donating efficiency of test compounds were used. Published experimental findings for the radical scavenging activity of the same compounds using methods such as Rancimat, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation and oxygen radical absorbance capacity were discussed. All the synthetic isochromans were predicted to be more potent hydrogen atom and electron donors than HT, though polarity may affect their performance in lipidic systems. Present findings point out that HT and examined isochromans prefer to scavenge free radicals via hydrogen atom transfer instead of electron donation and that allylic hydrogen atoms are expected to account for a higher activity in comparison to other phenolic antioxidants. The most potent hydrogen atom donor was the one bearing two catechol groups which can form stepwise a di-quinone and then scavenge additional radicals via allylic hydrogen atom donation and subsequent adduct formation. The total enthalpy required for all hydrogen atoms donated by test compounds was the most appropriate index of experimental activity prediction instead of common descriptors. [ABSTRACT FROM AUTHOR]

Chromatographic analysis of the ethyl acetate extract of the fungus Penicillium sp., which was isolated from the sediment of the hyper saline lake Wadi El-Natrun in Egypt, afforded two new isochromans ( 1 and 2 ) and a new isocoumarin derivative ( 3 ), along with six known compounds ( 4 – 9 ). The planar structures of new compounds were unequivocally elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy as well as HRESIMS. The relative configurations of the new compounds were established by analysis of the coupling constants as well as through ROESY experiments, while the absolute configurations were determined by comparison of the [ α ] D values and by plausible biosynthetic considerations. Compounds ( 1 – 6 ) were found to share (3 S ) configuration. All compounds demonstrated a weak to moderate cytotoxic activity against the murine lymphoma L5178Y cell line. [ABSTRACT FROM AUTHOR]

An unprecedented C–S formation protocol via the direct oxidative C(sp3)–H bond thioesterification of isochroman under metal-free conditions was developd. A series of isochroman derivatives could be afforded efficiently by the green, simple, and atom-economical method. [ABSTRACT FROM AUTHOR]

A new isochroman derivative, erythro-2-methyl-5-hydroxyphenylpropane-7,8-diol ( 1), and three known compounds including of (4S)-4,8-dihydroxy-3,4-dihydro-1(2H)-naphthalen-1-one ( 2), (4S)-4,6,8-trihydroxy-3,4-dihydro-1(2H)-naphthalen-1-one ( 3), and chrysogeside D ( 4), were isolated from Microsphaeropsis arundinis. Compounds 3 and 4 were first found in Microsphaeropsis. The antibacterial, antiphytopathogenic, and antioxidant activities of these compounds were evaluated. Compounds 1 and 4 inhibited Alternaria tenuissima, a pathogenic fungus causing root rot of Panax notoginseng with MICs at 64 μg/mL, which showed the ecological function of the endophyte for its host plant. [ABSTRACT FROM AUTHOR]

Indoor exposure to the spores and mycelial fragments of fungi that grow on damp building materials can result in increased non-atopic asthma and upper respiratory disease. The mechanism appears to involve exposure to low doses of fungal metabolites. Penicillium corylophilum is surprisingly common in damp buildings in USA, Canada and western Europe. We examined isolates of P. corylophilum geographically distributed across Canada in the first comprehensive study of secondary metabolites of this fungus. The sesquiterpene phomenone, the meroterpenoids citreohybridonol and andrastin A, koninginin A, E and G, three new alpha pyrones and four new isochromans were identified from extracts of culture filtrates. This is the first report of koninginins, meroterpenoids and alpha pyrones from P. corylophilum. These secondary metabolite data support the removal of P. corylophilum from Penicillium section Citrina and suggest that further taxonomic studies are required on this species. [ABSTRACT FROM AUTHOR]

Abstract: Oxa-Pictet–Spengler cyclization and microwave-assisted C–H arylation have been implemented as key steps in the synthesis of new isochroman heterocycles containing a 4,5,6a,7-tetrahydrodibenzo[de,g]chromene motif. These isochromans may be easily transformed to phenanthrene alkaloids via acidic cleavage of the isochroman ring and standard synthetic manipulations thereafter. The route described is attractive in that it provides access to two biologically interesting scaffolds in simple and high yielding synthetic steps. [Copyright &y& Elsevier]

A direct C(sp³)-H amination reaction of isochroman derivatives with arylamines was developed in the presence of iron(II) salt. A variety of isochroman derivatives and primary amines were selectively transformed into the corresponding oxidative coupling products in good to excellent yield under mild conditions [ABSTRACT FROM AUTHOR]

An efficient, stereo- and regioselective palladium-catalyzed 6-exo-dig intramolecular hydroarylation of propargyl ethers which provides a concise access to functionalized isochromans in high yields has been developed. A wide range of substrates possessing aromatic, aliphatic and heteroaromatic alkynes can be efficiently transformed into the targeted isochromans. Irrespective of the nature of the substrates, the cyclization follows highly selective stereo- and regiochemistry. [ABSTRACT FROM AUTHOR]

Abstract: Gold(I)-catalyzed reaction of ortho-alkynyl benzaldehyde tricarbonylchromium complexes with nucleophiles gave stereoselectively 1-anti- and syn-functionalized 1H-isochromene chromium complexes depending on the nature of nucleophile. By reaction with alcohols, 1-anti-alkoxy 1H-isochromene tricarbonylchromium complexes were obtained via gold benzopyrylium-type intermediates. On the other hand, carbon nucleophiles gave 1-syn-functionalized 1H-isochromene chromium complexes via stereoselective addition of nucleophiles to the activated carbonyl group and following cyclization. Methoxy group of 1-anti-methoxy-1H-isochromene chromium complex was substituted with carbon nucleophiles in the presence of Lewis acid to afford 1-anti-functionalized 1H-isochromene chromium complexes. These methods can be applied to the synthesis of enantiomerically pure trans- and cis-1,3-dimethylisochromans starting from a single planar chiral chromium complex. Similarly, ortho-alkynyl benzaldimine tricarbonylchromium complexes gave stereoselectively 1-syn- and anti-functionalized dihydroisoquinoline chromium complexes by gold(I)-catalyzed reaction with nucleophile. [ABSTRACT FROM AUTHOR]

The oxa-Pictet-Spengler reaction with various aldehydes and β-arylethanol yields 1-substituted-isochromans in the presence of bismuth triflate as catalyst in good yields. The method was extended to O,O-acetals to afford the corresponding 1,1-disubstituted-isochromans in good yields. These studies also provide insights into the catalytic role of triflic acid generated upon hydrolysis of Bi(OTf)3 by residual water. The low toxicity and easy handling of Bi(OTf)3 by comparison with triflic acid make these procedures an attractive method to provide isochromans in good to excellent yields. [ABSTRACT FROM AUTHOR]

• Rotational spectrum of isochroman complemented with theoretical calculations. • Parent species and all nine mono-substituted 13C isotopologues measured in natural abundance. • Semi-experimental structure was evaluated with vibrational corrections. The ground state rotational spectrum of isochroman (3,4-dihydro-1H-2-benzopyran, C 9 H 10 O) has been studied by using a pulsed jet Fourier transform microwave spectrometer in the range of 5-20 GHz, complemented with theoretical calculations. Accurate spectroscopic parameters including rotational and centrifugal distortion constants were determined for the parent species and all mono-substituted 13C isotopologues in natural abundance, which allow the determination of the accurate geometry of the carbon skeleton. The semi-experimental structure was evaluated by taking into account the vibrational corrections calculated from the B3LYP-D3(BJ)/6-311++G(d,p) anharmonic force field. The electrostatic potential surface above the benzene ring with different saturated cycles (n = 3-7) has been calculated at the MP2/6-311++G(d,p) level, implying that the electron withdrawing effect of electronegative O and N atoms can be transferred from the adjacent saturated ring to the benzene ring. [ABSTRACT FROM AUTHOR]

Abstract: An easy access to enantiopure isochromans through cross alkyne trimerization of a glucose derived dialkyne was developed. One of the synthesized isochromans was converted into a novel tricyclic nucleoside by simple transformations. [Copyright &y& Elsevier]

Abstract: A novel and concise synthesis of (±)-pseudodeflectusin (1), an antitumor isochroman derivative isolated from the culture broth of Aspergillus pseudodeflectus, was accomplished by starting from 4-(tert-butyldimethylsilyloxy)-1-pentyne (3) and diethyl 3-oxopentanedicarboxylate (5). [Copyright &y& Elsevier]

Abstract: Perfluorooctanesulfonic acid (PFOSA), Brønsted acid–surfactant-combined catalyst, efficiently catalyzes the Pictet–Spengler reactions of β-arylethyl carbamate derivatives with aldehydes in water. The present reaction is accelerated by the addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). PFOSA in HFIP–water (10v/v%) is also successfully applied to the oxa-Pictet–Spengler reactions of β-arylethyl alcohol compounds. [Copyright &y& Elsevier]

A new isochroman, 6-hydroxy-3-methylisochroman-5-carboxylic acid, and six known compounds were isolated from the culture of marine-derived mangrove fungus 1893#. Their structures were elucidated by analysis of spectroscopic data. [ABSTRACT FROM AUTHOR]

Abstract: Diastereoisomeric analogues of d4T having an isochroman core as the glycone moiety have been prepared in seven steps. Starting from phthalaldehyde, two chiral centres analogous to the α/β anomers of D/L sugars were created. The first was obtained enantiomerically pure via asymmetric dihydroxylation and the second via cyclisation of an aldehyde group with a primary hydroxyl group. Retention of chiral integrity at the C4 site enabled enantiomerically pure nucleoside analogues to be obtained. [Copyright &y& Elsevier]

Abstract: Molecules derived from tetralin, indane and isochroman are often used in the synthesis of fragrance materials. The two polycyclic musk fragrances AHTN (6-acetyl-1,1,2,4,4,7-hexamethyltetralin), HHCB (1,2,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-γ-2-benzopyran) and ADBI (4-acetyl-1,1-dimethyl-6-tert-butylindane) are derived from tetralin, isochroman and indane, respectively. In previous studies, AHTN and HHCB have been shown to antagonize estrogen receptors (ERs), both in vitro and in vivo. Here, we used two newly developed reporter gene assays, to examine the agonistic and antagonistic properties of several indane, tetralin and isochroman derivatives towards the human androgen receptor (AR) and aryl hydrocarbon receptor (AhR). Additionally, we also assessed (anti)estrogenicity of these compounds. A number of compounds showed weak estrogenic activity towards the human ERα. Several compounds showed (anti)estrogenic effects, starting at a concentration of 0.1μM. Surprisingly, almost all compounds were found to be AR antagonists, starting at 0.1μM. None of the compounds tested, showed either agonism or antagonism towards the AhR. Non-specific effects via crosstalk of the AhR and the ER or AR can therefore be ruled out. As far as we are aware, molecules derived from indane, tetralin and isochroman showing direct interaction with the ER and AR have not been reported previously. [Copyright &y& Elsevier]

[Display omitted] The reactivity of an electronically tuned nitroxyl radical catalyst for the oxidation of cyclic benzylic ethers has been investigated. The oxidation of phthalan resulted in oxidative cleavage of the saturated ring to give an aromatic dialdehyde. Additionally, oxidation of isochromans afforded isochromanones, which are often seen in natural products, in a rapid manner. [ABSTRACT FROM AUTHOR]

Supported catalysts are important tools for developing green-economy-based processes. Palladium nanoparticles (NPs) that are immobilized on two fibers developed as metal scavengers (i.e., Smopex®-234 and Smopex®-111, 1% w/w) have been prepared and tested in copper-free cyclocarbonylative Sonogashira reactions. Their catalytic activity has been compared with that of a homogeneous catalyst (i.e., PdCl2(PPh3)2). Pd/Smopex®-234 showed high activity and selectivity in the synthesis of functionalized heterocycles, such as phthalans and isochromans, even when working with a very low amount of palladium (0.2–0.5 mol%). The extension of Pd/Smopex®-234 promoted cyclocarbonylative reactions to propargyl and homopropargyl amides afforded the corresponding isoindoline and dihydrobenzazepine derivatives. A preliminary test on Pd NPs leaching into the solution (1.7 × 10−3 mg) seems to indicate that, at the end of the reaction, almost all of the active metal is present on the fiber surface. [ABSTRACT FROM AUTHOR]

Abstract: A series of isochromans were oxidized and brominated by using 1.2equiv of CuBr2 in CH3CN at reflux to give the corresponding bromo benzaldehydes in moderate yields. A plausible mechanism for this transformation has been suggested. [Copyright &y& Elsevier]

Isochromans are well recognized heterocyclic compounds in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Medicinal chemistry investigators have synthesized drug-like isochroman candidates with multiple medicinal features including central nervous system (CNS), antioxidant, antimicrobial, antihypertensive, antitumor and anti-inflammatory agents. Simultaneously, SAR (Structure-Activity Relationship) analysis has drawn attentions among medicinal chemists, along with a great deal of derivatives have been derived for potential targets. In this article, we thoroughly summarize the biological activities and part of typical SAR for isochroman derivatives reported on existing literatures and patents, wishing to provide an overall retrospect and prospect on the isochroman analogues. Image 1 • The isochroman structural motif is a critical element of drug candidates aimed at different biological end-points. • Researches on chemical syntheses and modifications of the isochroman analogues have been carried out to drug-like candidates with broad range of medicinal properties. • This review summarizes the activity and SAR for isochromans, wishing to give perspective on the isochroman derivatives. [ABSTRACT FROM AUTHOR]