Search

Poly[(thiophene)‐alt‐(6,7‐difluoro‐2(2‐hexyldecyloxy)quinoxaline)] (PTQ10) emerges as a promising candidate for donor materials in organic solar cells (OSCs) due to its high efficiency, simplified synthesis, and cost‐effectiveness. The acceptor unit of PTQ10 is derived from the alkylation of 5,8‐dibromo‐6,7‐difluoroquinoxaline‐2‐ol, emphasizing the importance of its economical synthesis for commercial viability. This study investigates triflic acid‐assisted regioselective bromination of quinoxaline derivatives and proposes an alternative synthetic pathway for PTQ10. The developed route benefits from concise synthetic steps, a dependable procedure, and high overall yield. Starting with the condensation of 4,5‐difluorobenzene‐1,2‐diamine with ethyl oxoacetate to yield 6,7‐difluoroquinoxaline‐2‐ol, subsequent triflic acid‐assisted regioselective bromination produces 5,8‐dibromo‐6,7‐difluoroquinoxaline‐2‐ol in high yield. Alkylation under Mitsunobu reaction conditions yields 5,8‐dibromo‐6,7‐difluoro‐2‐(2‐hexyldecyloxy)quinoxaline, followed by polymerization with 2,5‐distannylated thiophene under Stille reaction conditions to afford PTQ10. This research provides insights into efficient synthetic strategies for PTQ10, advancing its potential for commercial application in OSCs. [ABSTRACT FROM AUTHOR]

In order to improve the drug-likeness qualities, the antimalarial endochin-like quinolone (ELQ) scaffold has been modified by replacing the 4-(trifluoromethoxy)phenyl portion with an isoidide unit that is further adjustable by varying the distal O-substituents. As expected, the water solubilities of the new analogs are greatly improved, and the melting points are lower. However, the antimalarial potency of the new analogs is reduced to EC50 > 1 millimolar, a result ascribable to the hydrophilic nature of the new substitution. [ABSTRACT FROM AUTHOR]

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische's Ir-catalyzed crotylation, Brown's borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B. [ABSTRACT FROM AUTHOR]

The cluster of four skipped exo‐methylene substituents on the "northern" wing of limaol renders this dinoflagellate‐derived marine natural product unique in structural terms. This arguably non‐thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty‐fold per run. Key‐to‐success was a gold‐catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate‐controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much‐improved route to the "northern" sector was established by leveraging the power of asymmetric hydrogenation of a 2‐pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity. [ABSTRACT FROM AUTHOR]

A successful approach for the construction of steroid dimers with a hydroquinone linker under PBu3/TMAD/Et3N/toluene conditions is described. This study provided a new one‐step methodology for the design and synthesis of bis‐steroidal 1,4‐phenylene diethers using mild and effective reagents. [ABSTRACT FROM AUTHOR]

The Mitsunobu reaction is a widely used organic reaction that allows for the replacement of hydroxyl groups with other compounds. It has been extensively studied, with various investigations into its mechanism and intermediates. The reaction has some drawbacks, but many variations and catalytic processes have been developed to address these issues. The studies discussed in the article provide evidence for different intermediates and explore factors that influence the reaction outcome. While there are still unanswered questions, the Mitsunobu reaction is recognized as a valuable and predictable organic reaction. [Extracted from the article]

Objective: Dehydroepiandrosterone plays an important role in the human beings due to its ability to be converted into androgens and oestrogens. The aim of this paper is to synthesize a series of novel dehydroepiandrosteronyl 1,2,3-triazole derivatives and study the antitumor activity of the synthesized compounds. Methods: Novel dehydroepiandrosteronyl 1,2,3-triazole derivatives were synthesized across the Mitsunobu and click reaction, respectively. The cytotoxicities of the synthesized compounds against HeLa, HGC-27, and HEK-293T cells were determined by MTT assay. Results and Discussion: The results showed that compound (V) (3R,8R,9S,10R,13S,14S)3-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro17H-cyclopenta[a]phenanthren-17-one had better inhibitory activity against the tumor cell lines tested. The IC50 value of inhibitory activity on human cervical cancer cell (HeLa) and human gastric cancer cell (HGC-27) was 33.6 and 22.3 μmolL–1, respectively. Conclusions: This work provides useful strategies for the design and synthesis of new steroidal antitumor drugs. The synthesized compounds have certain inhibitory activity on tumor cell growth and proliferation, but have little damage on normal cells, which deserves further study. [ABSTRACT FROM AUTHOR]

The paper presents the photomechanical effect generated in new azo side-chain polyimides synthesized through a post-functionalization strategy involving the Mitsunobu reaction. Prepared azo polyimide foils were irradiated by a 405 nm diode-laser beam (intensity, I = 100 mW/cm²; polarization, Eǀǀx) for the generation of the photomechanical effect. Despite the low content of azo chromophore (substitution of the hydroxyl group was in the range of 7–35%) and thick cantilevers (thickness ~35 µm), bending angles were in the range of 30–40°. Thermal unbending was not observed for 12 months after turning off the excitation light. Our investigation showed that, despite the low content of azo chromophore, it is possible to achieve photodeformation under polarized light. To the best of our knowledge, this is the first example of the photomechanical response of azo pyridine polymers. [ABSTRACT FROM AUTHOR]

Selenosugars are gaining growing interest due to their antioxidant efficacy, and their ability to inhibit glycosidases, repair skin tissue or reduce endothelial dysfunction. Among selenosugars, those in which selenium replaces heterocyclic oxygen in a 5-membered sugar were our focus, and their coupling with phenolic compounds appears to be a strategy aimed at producing new compounds with enhanced antioxidant efficacy. In this context, the Mitsunobu reaction has been advantageously explored to obtain trans-p-coumaroyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, trans-caffeoyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, and trans-feruloyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose. These compounds underwent removal of the iso-propylidene group, to provide the corresponding hydroxycinnamoyl-1,4-deoxy-4-seleno-d-ribose. All compounds were characterized by Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). This latter technique was pivotal for ensuing cellular metabolomics analyses. In fact, after evaluating the anti-radical efficacy through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, which underline the massive role of the phenolic moiety in establishing efficacy, the compounds, whose cytotoxicity was first screened in two highly oxidative-stress-sensitive cells, were tested for their wound healing properties towards human HaCaT keratinocytes cells. Caffeoyl- and feruloyl selenosugars exerted a dose-dependent repair activity, while, as highlighted by the metabolomic approach, they were poorly taken up within the cells. [ABSTRACT FROM AUTHOR]

A Mitsunobu process performed under neat grinding conditions, using a mixer mill, is reported. It proceeds in the absence of reaction solvent and in short reactions times (10–20 min). A broad substrate scope encompassing primary and secondary alcohols, as well as oxygen, nitrogen, sulfur, and carbon‐centered nucleophiles is demonstrated. Application to the functionalization of a selection of APIs is shown, also. The developed process is amenable to scale up on a planetary ball‐mill, yielding over 2 grams of product. Finally, a representative alcohol is inverted with excellent stereoselectivity. [ABSTRACT FROM AUTHOR]

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by‐products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu‐type reaction, which features azo‐free alcohol activation and broad substrate scope. This user‐friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple‐step synthesis of a drug candidate. [ABSTRACT FROM AUTHOR]

This report describes the one‐pot direct N‐acylation of indazole with carboxylic acids using our previously developed 4‐(N,N‐dimethylamino)pyridine N‐oxide (DMAPO)/di‐tert‐butyl dicarbonate (Boc2O) system. This simple system provides N1‐acyl indazoles in high yield with high N1 selectivities and does not require the use of activated derivatives of carboxylic acids or high temperatures. This new method exhibits a wide substrate scope (>40 examples). In addition, a new synthesis of N1‐functionalized alkyl indazoles utilizing N1‐acyl indazoles as starting materials was achieved. This stepwise protocol is useful for the selective synthesis of structurally diverse N1‐functionalized alkyl indazoles, which are difficult to synthesize by other methods such as the Mitsunobu reaction and classical SN2 alkylation of indazole. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) continues to be a major global health challenge and a leading cause of death from infectious diseases. Inspired by the results from a previous work by our group on antimycobacterial N-alkylnitrobenzamides, which are structurally related to the nitrobenzamide family of decaprenylphosphoryl-β-d-ribose oxidase (DprE1) inhibitors, the present study explored a broad array of substituted benzamides. We particularly focused on previously unexplored 3,5-dinitrobenzamide derivatives. Starting with 3,5-dinitrobenzoic acid, we synthesized a diverse library of amides, incorporating both linear and cyclic amine moieties and also assessed the impact of terminal aromatic groups connected through ether, ester, or amide bonds on the bioactivity of the compounds. The synthesis primarily utilized nucleophilic addition/elimination, SN2, and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of linker. The most interesting compounds (c2, d1, and d2, MIC = 0.031 μg/mL) exhibited activities against Mycobacterium Tuberculosis (Mtb) H37Rv comparable to isoniazid. Complementary computational studies helped elucidate potential interactions with DprE1, enhancing our understanding of the molecular basis of their action. Our findings suggest that the most active compounds provide a promising foundation for the continued development of new antimycobacterial agents. [ABSTRACT FROM AUTHOR]

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anticancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O-alkyl silybins derivatives were synthesized by the Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4), and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of eighteen new derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by the DPPH assay showed a very pronounced activity depending on the tyrosyl moiety (HTYR > MTYR >> TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin-based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a, and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a, and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, Western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials. [ABSTRACT FROM AUTHOR]

This article discusses the total synthesis of two securinega alkaloids, 4α-hydroxyallosecurinine and securingine F, which have potential for biofunctional derivatizations. The presence of a functional handle is crucial for the development of natural-product-based drugs and antibody-drug conjugates (ADCs). The synthesis of these alkaloids involved a series of reactions, including a Michael addition-based union, epimerization, and intramolecular aza-Michael addition. The successful synthesis of these alkaloids opens up possibilities for further research and the synthesis of other complex securinega alkaloids with a C4-hydroxy handle. [Extracted from the article]

This article explores the process of synthesizing pancracine, an alkaloid, through the selective hydrogenation of an indole derivative. It emphasizes the importance of certain carbon and heteroatom structures in drug development and the advantages of saturated cores in accessing specific binding sites in proteins. The article also discusses the challenges and strategies involved in achieving selective hydrogenation of certain compounds. The researchers successfully synthesized a key intermediate for pancracine and investigated the reduction of another intermediate to obtain the desired product. They suggest that this hydrogenation strategy could be applied to the synthesis of other alkaloids with similar structures. [Extracted from the article]

A practical synthesis of (±)-entecavir has been developed on the basis of Corey (±)-lactone diol. The key stage is the synthesis of (1R*,3R*,4S*)-4-(1-ethoxyethoxy)-3-[(1-ethoxyethoxy)methyl]-2-methylidene-cyclo-pentan-1-ol by oxidative decarboxylation of 2-{(1S*,2R*,3S*,5R*)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-(1-ethoxyethoxy)-2-[(1-ethoxyethoxy)methyl]cyclopentyl}acetic acid with lead tetraacetate. [ABSTRACT FROM AUTHOR]

Azo compounds are versatile in multifarious areas. They are crucial reagents in Mitsunobu reactions and dehydrogenations. However, the azo compounds or their corresponding hydrazides have never been investigated in the catalytic dehydrogenation of tertiary amines. Herein, we report a co-catalytic system using CuCl, 4-(dimethylamino)pyridine (DMAP), and 2-(4-nitrophenyl)hydrazine-1-carboxylate for the aerobic oxidative dehydrogenation of tertiary indolines to their corresponding indoles. [ABSTRACT FROM AUTHOR]

A synthesis route of a novel phosphoramide morpholinoline-oligoguanylate monomer using guanosine as raw material was developed.Based on the protection of the amino group on the base and 5’-OH in ribose, the ribose ring is converted into a morpholine ring to obtain the protected morpholine guanosine.A triphenylmethylation reaction was carried out on the morpholine ring and purine 6-O position was modified using the Mitsunobu reaction.N,N-dimethylaminophosphorylation reaction is performed on the deprotected hydroxyl group to synthesize the target product.In this study, the conditions of the Mitsunobu reaction and phosphorylation reaction were optimized.Under optimized conditions, the total yield of the new synthetic route was 14.1%.The structure of intermediate products and target products were characterized by LC-MS, ¹H NMR and 31P NMR. [ABSTRACT FROM AUTHOR]

This document is a scientific article discussing the synthesis and characterization of various chemical compounds. The authors provide detailed information about the experimental procedures, yields, and physical properties of the compounds. They also include data from spectroscopic techniques such as infrared (IR) spectra, nuclear magnetic resonance (NMR) spectra, and high-resolution mass spectrometry (HRMS) results. The information presented in this article can be valuable for researchers studying organic chemistry and conducting similar experiments. The authors acknowledge funding from the NSF MRI program and dedicate their work to the memory of Dr. Michael P. Jennings. Additional supporting information and a graph can be found online. [Extracted from the article]

The given text is a scientific research article that discusses the use of the Mitsunobu reaction for synthesizing chiral alcohols. The authors developed stabilized phosphorane reagents to overcome the limitation of low acidity in the reaction. They demonstrate the iterative assembly of chiral alcohols using these reagents, which can be used to synthesize biologically active compounds with multiple stereogenic centers. The article provides detailed information on the synthesis and characterization of various chemical compounds, including their physical and chemical properties, as well as the experimental procedures used. This information can be valuable for researchers studying organic chemistry and chemical synthesis. [Extracted from the article]

The synthesis and 3D-conformation of several novel benzene-1,3-disulfonamides-containing 11- to 13-membered heterocycles have been achieved. Double Mitsunobu annulation was effective for the construction of medium to large ring systems in moderate chemical yields. In addition, the flexibility of sulfonamide moieties in these rings was determined by X-ray crystal structural analysis. [ABSTRACT FROM AUTHOR]

This document discusses the synthesis of various compounds derived from quinolin-4(1H)-one, which have potential applications in medicinal chemistry. The authors present a new method for synthesizing these compounds using regioselective phosphonylation and diastereoselective reduction, followed by a Mitsunobu reaction. The resulting compounds were analyzed and characterized using spectroscopic techniques. The document provides detailed information on the synthesis process, yields, physical properties, and spectroscopic data for each compound. The authors also acknowledge the support of individuals and provide additional supporting information. [Extracted from the article]

Herein, we report the preparation of enantiomerically pure forms of 2,3-dihydrobenzofuran-3-ol (1), chroman-4-ol (2), thiochroman-4-ol (3), 1-(furan-2-yl) ethanol (5) and 1-(thiophen-2-yl) ethanol (6), through a kinetic resolution catalysed by Candida antarctica lipase B/Na2CO3 hydrolysis sequence in organic media. The (R)-furnished alcohols and the (S)-remained acetates are recovered enantiopures (ee >99%, E ≫ 200, Conv = 50%). Those ideal enzymatic kinetic resolution (EKRs) are well incorporated to the Mitsunobu inversion protocol in a one pot procedure to give (S)-heterocyclic acetates (1a–3a) in good to high enantiomeric excess (88%–92% ee). Whilst, the (S)-heteroaromatic acetates (5a and 6a) are given with moderate enantiomeric excess (51%–62% ee). All the (S)-acetates are given in good isolated chemical yields (>80%) allowing to overcome the maximum of 50% yield which could be usually reached in a regular kinetic resolution processes. [ABSTRACT FROM AUTHOR]

In order to improve the drug-likeness qualities, the antimalarial endochin-like quinolone (ELQ) scaffold has been modified by replacing the 4-(trifluoromethoxy)phenyl portion with an isoidide unit that is further adjustable by varying the distal O-substituents. As expected, the water solubilities of the new analogs are greatly improved, and the melting points are lower. However, the antimalarial potency of the new analogs is reduced to EC50 > 1 millimolar, a result ascribable to the hydrophilic nature of the new substitution.

A simple and rapid access to fluorinated dithioesters was developed by a one-pot sequence corresponding to a Grignard reaction—Mitsunobu type substitution. These activated dithioesters have shown excellent reactivity in an aminolysis reaction from simple or more complex primary amines such as cinchona alkaloids. A stoichiometric amount of amine was sufficient to prepare various thioamides, including a 4-styrenylthioamide cinchonidine monomer, under environmentally friendly conditions, at room temperature, and in a very short time. [ABSTRACT FROM AUTHOR]

[4] In 2012, Xie and co-workers reported a ring-closing metathesis and a diethyl aluminum 2,2,6,6-tertramethylpieridinone mediated epoxide isomerization route to construct the five-membered carbocyclic core of Entecavir, and the total synthesis was finished in 10 steps with 21% overall yield. Keywords: Entecavir; synthesis; stereoisomers; stereoselective; hepatitis B EN Entecavir synthesis stereoisomers stereoselective hepatitis B 3109 3112 4 09/11/23 20231004 NES 231004 Graph Hepatitis B is one of the most prevalent viral diseases in the world and about three hundred million individuals worldwide are chronically infected with HBV. At the beginning of our study, we planned to synthesize stereoisomer B ENT1 b by a modified method developed by Bisacchi for the synthesis of Entecavir. In this manuscript, we report the first synthesis of three stereoisomers of Entecavir. [Extracted from the article]

The total synthesis of 14 membered macrolide Pestalotioprolide C and C7-epi- Pestalotioprolide C were accomplished starting from commercially available D-Mannitol by Stereoselective synthetic approach. The key reactions involved are Mitsunobu reaction, Regioselective ring opening of chiral epoxide and ring-closing metathesis reactions (RCM). [ABSTRACT FROM AUTHOR]

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anticancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O-alkyl silybins derivatives were synthesized by the Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4), and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of eighteen new derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by the DPPH assay showed a very pronounced activity depending on the tyrosyl moiety (HTYR > MTYR >> TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin-based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a, and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a, and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, Western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Keywords: 2,2'-bipyridine ligand; C3-ACBP; column chromatography free; zinc chloride; gram scale EN 2,2'-bipyridine ligand C3-ACBP column chromatography free zinc chloride gram scale 2483 2486 4 07/31/23 20230817 NES 230817 Graph The chiral bidentate I N i , I N i -ligands play an essential role in asymmetric catalysis and great progress has been achieved in their synthesis and applications in recent decades. For both steps, column chromatography for the purification of the target products was conducted, which is impractical and unsustainable for the synthesis of chiral intermediate ( I S i , I S i )- B 3 b and the final bipyridine ligand at a large scale. To obtain the ligand, an excess amount of sodium hydroxide was added to precipitate the copper ion and neutralize the hydrochloride salt to release the free chiral bipyridine ligand. Comparing the mass of precipitate before and after dissociating zinc chloride, the ratio of ( I S i , I S i )- B 3 b to zinc chloride was calculated to be 1:1. [Extracted from the article]

Keywords: Arabinoxylan ferulate; Biomass; Carbohydrates; Mitsunobu reaction; Synthetic methods; Xylotriose model; Reducing end-groups EN Arabinoxylan ferulate Biomass Carbohydrates Mitsunobu reaction Synthetic methods Xylotriose model Reducing end-groups 7389 7392 4 08/16/23 20230801 NES 230801 Maintext In our recent article (Elschner et al. [4]), we reported about the Mitsunobu esterification of arabinoxylan with ferulic acid at position 5 of the arabinose side chain. The standard Mitsunobu reaction for the esterification of carboxylic acids with alcohols takes place according to a dehydrative S SB N sb 2 process enabled by reductive triphenylphosphine and diisopropyl azodicarboxylate as oxidant. [Extracted from the article]

2‐Nitroimidazole based PET tracers are widely used for non‐invasive hypoxic tumor diagnosis. In this context, we report here a general method based on a central Mitsunobu reaction to easily access 2‐nitroimidazole precursors. Optimization of fluorination conditions is described and successfully applied to the radiofluorination of the 2‐nitroimidazole precursors. Moreover, the radiosynthesis of a new potential hypoxia PET tracer is also described. Finally, this article presents a SFC analytical method allowing both an easy monitoring of the fluorination reactions and the measurement of partition coefficients (logP). [ABSTRACT FROM AUTHOR]

(5R)-Cleistenolide and a few related analogues have been synthesized starting from d-glucose. The key steps of the synthesis included a Z-selective Wittig olefination and an intramolecular Mitsunobu reaction with an inversion of configuration at the C-5 position. In vitro antiproliferative activity of synthesized compounds was tested on a panel of eight human tumour cells and against a single normal cell line (MRC-5). The majority of tested compounds showed strong antiproliferative effects on certain human tumour cells and all of them showed negligible toxicity to normal foetal lung fibroblasts (MRC-5). The most active compound obtained in this work is lactone 5, which in MDA--MB 231 cell culture showed the same activity as doxorubicin (IC50 0.09 μM). Strong antiproliferative activities of analogues 2, 5 and 6 were recorded in the K562 cell line (IC50 0.21, 0.34 and 0.33 μM, respectively), in which they showed very similar activities to doxorubicin (IC50 0.25 μM). A performed SAR study revealed that a change in the stereochemistry at the C-5 position may increase the activity of resulting stereoisomers. [ABSTRACT FROM AUTHOR]

Alkylation of thiopurine derivatives with alcohols by the Mitsunobu reaction are reported in moderated to good yields. The method was applied in synthesis of number of thiopurine and thiopurine ribosides derivatives. [ABSTRACT FROM AUTHOR]

The morphinan alkaloid (–)-thebaine is an industrially important chemical intermediate deployed in the semi-synthesis of various opioid medicines. Here, a seven-step total synthesis of this natural product is reported from simple, commercially available starting materials. The pivotal aryl allyl ether substrate, which is obtained through successive Suzuki-Miyaura cross-coupling and Mitsunobu substitution reactions, was engaged in a double-Heck cyclization sequence. The tetracyclic product of these processes was subjected to a photochemical hydroamination reaction that generated a N -Boc piperidine derivative embodying the full pentacyclic morphinan framework. Over a further three simple steps, this last compound was converted into (–)-thebaine. [ABSTRACT FROM AUTHOR]

This method offers several advantages over traditional methods for the asymmetric synthesis of β‐azido esters. First, the use of N‐acetyl camphorsultam allows for excellent stereoselectivity in the aldol reaction, which is crucial for the subsequent Mitsunobu reaction. Second, the use of trimethylsilyl azide (TMSN3) instead of hydrazoic acid (HN3) eliminates the need for handling a highly toxic and explosive reagent, making the process safer and easier to carry out. Third, the use of basic conditions for the Mitsunobu reaction allows for the reaction to proceed efficiently without the formation of the undesired silyl ethers. [ABSTRACT FROM AUTHOR]

Compounds with 1‐aminoindane motif exhibit vital biological activities in the central nervous system. Therefore, it is very important to synthesize new compounds with this moiety and to obtain them in high enantiopurity. In this study, novel substituted 1‐aminoindane derivatives were synthesized, and their asymmetric resolutions were carried out. Accordingly, the reduction of 1‐indanones with NaBH4, conversion of alcohols to azides via an alternative Mitsunobu reaction followed by reduction of azides afforded (±)‐1‐aminoindane hydrochloride or hydrobromide salts. Amine salts were converted into their free amines by using excess amount of Et3N and then in situ occurred free (±)‐amines were reacted with (R)‐O‐acetylmandeloyl chloride to give diastereomeric mixtures. The crystallization of the diastereomeric mixtures followed by hydrolysis yielded the corresponding asymmetric amines with high enantio‐purity. [ABSTRACT FROM AUTHOR]

Immunomodulators are assigned as a robust tool for the treatment of various medical conditions like AIDS, cancer and autoimmune diseases. In this work, we have synthesized a series of fluoxetine-based small-molecule immunomodulators. Molecules were synthesized by a convergent strategy, where mitsunobu reaction was conducted to synthesize the common starting material. The novel analogues displayed immunomodulatory potential as indicated by the anti-inflammatory effect derived through the compound's T cell proliferation inhibitory property. The synthesized novel analogues manifested encouraging biological responses, assure their application as immunomodulators. [ABSTRACT FROM AUTHOR]

Chiral diketopyrrolopyrroles appended with enantiomeric ethyl lactate functions through an ether linkage to the aryl backbone of the chromophore were synthesized via the Mitsunobu reaction. The molecules have good solubility and excellent optical properties, high molar absorption coefficients, and fluorescence quantum yields. Helical aggregates with circular dichroism arising from the supramolecular arrangement are seen in both solution and thin films, and the aggregates also display circularly polarized luminescence (glum ≈ ±0.1). The molecules assemble to give monolayers on graphite and precipitate from solution forming supramolecular twisted tapes hundreds of microns long. [ABSTRACT FROM AUTHOR]

The combination of the alkoxyphosphoranes, Ph2P(OR)(O2C6Cl4) and the borane B(C6F5)3 generates the zwitterions 3 which act as FLP to effect the alkylation of several nucleophiles affording C−C, C−N, C−H and C−Cl coupling products. A DFT study shows the reaction proceeds via an FLP activation pathway generating an alkoxyphosphonium intermediate which effects the alkylation of the nucleophiles, akin to the Mitsunobu reaction. [ABSTRACT FROM AUTHOR]

Derivatives of cinnamic acid have several pharmacological actions, such as antimicrobial activity. Therefore, in the present study, a series of fourteen alkyl and aryl derivatives from (E)-2-nitrocinnamic acid were obtained using Fischer esterification, nucleophilic substitution with halides, and Mitsunobu reaction. Esters were evaluated for antifungal activity against several strains of Candida spp. using nystatin as a positive control. Among the synthetic derivatives obtained, nine are compounds unprecedented in the literature. The characterization of chemical structures was carried out using the techniques of IR, 1H-NMR and 13C-NMR spectroscopy, and high-resolution mass spectrometry. Isopropyl 2-nitrocinnamate (4) was the compound that showed the best antifungal activity (MIC = 513.52 μM) against all fungal strains, followed by compound perillyl 2-nitrocinnamate (14) with MIC = 390.99–781.98 μM. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Polymer functionalization is a powerful tool to prepare polymers with diverse structures without the need of synthesizing monomers or performing polymerization reactions. Polymers that are difficult to be synthesized using direct polymerization reactions can be accessed using polymer functionalization. We herein present Mitsunobu derivatization of poly(vinyl alcohol) (PVA) to convert the hydroxyl groups into diverse functional groups. Partial acetalation strategy is applied to improve solubility of the PVA derivatives in tetrahydrofuran, and more importantly, the acetals can act as protecting groups so that functionalized copolymers are produced. Diverse functions can be introduced into PVA derivatives by installing different functional groups. Transparent, colorless, flexible, and scalable UV‐shielding membranes are conveniently prepared in one step using this method. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Polymer functionalization is a powerful tool to prepare polymers with diverse structures without the need of synthesizing monomers or performing polymerization reactions. Polymers that are difficult to be synthesized using direct polymerization reactions can be accessed using polymer functionalization. We herein present Mitsunobu derivatization of poly(vinyl alcohol) (PVA) to convert the hydroxyl groups into diverse functional groups. Partial acetalation strategy is applied to improve solubility of the PVA derivatives in tetrahydrofuran, and more importantly, the acetals can act as protecting groups so that functionalized copolymers are produced. Diverse functions can be introduced into PVA derivatives by installing different functional groups. Transparent, colorless, flexible, and scalable UV‐shielding membranes are conveniently prepared in one step using this method. [ABSTRACT FROM AUTHOR]

Intravascular thrombus formation is one of the main causes of such deadly diseases and pathologies as ischemic heart disease, ischemic stroke, pulmonary embolism, atrial fibrillation, and venous thromboembolism [1, 2]. That is why the development of new approaches for preventing intravascular blood coagulation is an important task for biochemistry and biotechnology. Most of biomolecules that target clotting factors. However, in our study we focused on another type of molecules, which are direct inhibitors of fibrin polymerization. As a scaffold, we have used a calix[4]arene molecule because of its tunable diversity at both upper and lower rims, its pre-organized nonpolar cavities, pre-organized ion-bonding sites and well-defined conformations [3]. Previously we have shown that calix[4]arenes are active inhibitors of fibrin polymerization process. Binding to the ‘A’-knob of fibrin desAB molecule calix[4] arenes prevents knob-hole interactions between different fibrin molecules thus suppressing clotting. Recent studies proved the efficacy of sodium salt of 5, 11, 17, 23-bis(dihydroxyphos phoryl)methylcalix[4]arene (C-145) as an effective anticoagulant agent [4, 5]. Molecular dynamic studies of C-145 demonstrated the importance of conformation of the macrocycle for its fibrin-binding activity. In particular calyx[4]arene has two different conformations of its cup (the macrocycle) that can be described as ‘1,3-alternate’ (opened) or ‘conus-conformation’ (fixed). Aim. The purpose of the present study was to develop a method for the fixation of ‘fixed’ conformation for estimation of the impact of calix[4]arene structure on the efficacy of its anticoagulant activity. This was achieved by substitution of the lower rim of C-145 analogue. Metods. Calix[4]arene C-145 was obtained according to the method described in [6] with one additional step that included Mitsunobu reaction in order to obtain disubstituted calixarene C-145F (Fig. 1). Modeling of 3D-structure of calix[4]arene C-145 and its analogue C-145F was performed in Maestro, Schrodinger software. Calix[4]arene C-145F (compound 6) was obtained in 4 steps starting with Duff reaction. Calix[4]arene methylene-bis-phosphonic ester 3 was prepared via addition of diisopropylphosphite in presence of metallic sodium to the parent calix[4]arene aldehyde 2. Further steps included Mitsunobu reaction, that afforded dipropoxycalix[4]arene 5 with rather good yields (80%), following the hydrolysis step that resulted in compound 6 in almost quantitative yield. Results. Using a 2D NMR-NOESY spectroscopy, we can observe a distinct cross-peak between an aromatic singlet with a chemical shift on 7.72 ppm and protons of isopropyl group with a chemical shift on 1.62 ppm, which are moved in the strong field (Fig. 2). This correlation proves us their steric proximity, that can be observed only in conus-conformation (Fig. 3, A), not in the 1,3-alternate. So, in this work we confirmed that disubstituted calix[4]arenes (low-rim modification) have fixed conus conformation. NMR spectroscopy proves us that calix[4]arene C145F exists in fixed conus-conformation. Discussion. Presented experiment represents how easily we can modify calix[4]arene cup in order to obtain molecule with new chemical and physical properties. The fine-tuning and incorporation of different ligating sites in the calix[4]arene scaffold may be used to produce numerous molecules, forming a library of compounds. Comparison of the action of fibrin polymerization of calix[4]arene molecules with fixed and opened conformations will allow to estimate the role of different conformation in fibrin recognition and will support targeted design of even more effective calix[4]arene-based inhibitors of blood clotting in future. Conclusions. The easy method of the fixation of conus conformation of calix[4]arene cup will be useful for synthesis of novel functionally active compounds. We believe that further development and study of different calix[4]arenes will help scientists to obtain bioactive molecules that could be prospective anti-thrombotic drugs. [ABSTRACT FROM AUTHOR]

Arabinoxylan ferulate representing a macromolecular LCC model valid for annual plants is synthesized under Mitsunobu conditions. The content of ferulic acid ester is tuned by the reaction conditions achieving degree of substitution values from 0.09 to 0.45. Utilization of the chloride-free solvent N-methyl-2-pyrrolidone allows the design of pure Mitsunobu products without occurrence of deoxychloro moieties arising from Appel type reaction. 2D NMR experiments reveal nature-identical structure of ferulate moieties present at position 5 of the arabinose side chain. Enzymatic dehydrogenation polymerization of coniferyl alcohol on ferulate anchor groups under homogeneous conditions lead to β -O-4, β -5, and Hibbert ketone structures identified by Py-GC-MS. The results are valuable to study structure-property relationships within the formation of natural and non-native lignins. [ABSTRACT FROM AUTHOR]

(R)-Tenofovir phenyl ester ((R)-1) and (R)-tenofovir diphenyl ester ((R)-2) are key intermediates for the practical synthesis of tenofovir alafenamide fumarate, which is a mainstay antiretroviral for the treatment of chronic hepatitis B and HIV-1 infections. This article deals with the chiral analysis of (R)-1 and (R)-2 against their respective optical impurity (S)-tenofovir phenyl ester ((S)-1) and (S)-tenofovir diphenyl ester ((S)-2) using a polysaccharide-coated chiral stationary phase (CSP) by normal-phase high-performance liquid chromatography (HPLC). To this end, a chiral synthetic strategy for (S)-2 was efficiently executed capitalizing on a classical Mitsunobu reaction to stereospecifically invert the configuration of chiral carbon in readily accessible (R)-HPA ((R)-4) to deliver (S)-HPA ((S)-4), from which (S)--tenofovir ((S)-3) was in turn prepared and further transformed into (S)-2. With reference substance (S)-2 in hand, a chiral analytical method for (R)-2 using Chiralpak AD-H as CSP by normal-phase HPLC has been developed and validated. The validation results indicated that this chiral analytical method has been achieved with satisfactory separation effect, high sensitivity, and good precision and accuracy, and thus can be deployed for the determination of optical impurities in samples of (R)-1 (via derivation to (R)-2) and (R)-2.

Synthesis of the originally assigned structure of the styryl tetrahydropyranol-dihydropyranone natural product cryptoconcatone H from C 2-symmetric (±)-1,8-nonadiene-4,6-diol is reported. Desymmetrization by Mitsunobu reaction with crotonic acid established the requisite inter-ring stereochemical relationship and was followed by a highly diastereoselective Re2 O7-catalyzed Prins cyclization with cinnamaldehyde to construct the 2,4,6- cis -tetrahydropyranol ring. Ring-closing metathesis resulted in formation of the dihydropyranone ring and completed the synthesis in three steps and 32% overall yield. The brevity of the synthesis is the result of the recognition of hidden, inter-ring symmetry in the target and the ensuing choice of an appropriately symmetric diol as our starting material. [ABSTRACT FROM AUTHOR]

A small library of 6-O-sucrose monoester surfactants has been synthesized and tested against various microorganisms. The synthetic procedure involved a modified Mitsunobu reaction, which showed improved results compared to those present in the literature (higher yields and larger scope). The antifungal activities of most of these glycolipids were satisfactory. In particular, sucrose palmitoleate (URB1537) showed good activity against Candida albicans ATCC 10231, Fusarium spp., and Aspergillus fumigatus IDRAH01 (MIC value: 16, 32, 64 µg/mL, respectively), and was further characterized through radical scavenging, anti-inflammatory, and biocompatibility tests. URB1537 has been shown to control the inflammatory response and to have a safe profile. [ABSTRACT FROM AUTHOR]

An important goal of modern synthetic chemistry is the development of highly efficient and selective processes that minimize the formation of waste, which are desirable for economy and environmental requirements. The classic Mitsunobu reaction has been adopted widely for converting alcohols into numerous functional groups and undergoes an inversion of stereochemistry in SN2 reaction when secondary alcohols are employed. However, the reaction is far from ideal in terms of its environmental impact, requiring stoichiometric amounts of a phosphine (III) and an azodicarboxylate, and producing stoichiometric amounts of hydrazine and phosphine oxide wastes. The first attempt to access the catalytic Mitsunobu reaction dates back to 2006 by Toy's group and since then, several groups including Taniguchi, O'Brien, Aldrich, Denton and their co‐workers have opted for this promising alternative. Generally, the substantial progress has been made in the development of catalytic Mitsunobu reaction involving redox‐driven and redox‐neutral processes. The elegant redox‐driven catalytic system applies either external reductants or oxidants to recycle azo or phosphine reagents, while the preeminent redox‐neutral catalytic system is undergoing the activation step to proceed. This review summarizes the related developments in the recent two decades and presents the future research direction. [ABSTRACT FROM AUTHOR]

The 3C-like protease (also known as Mpro) plays a key role in SARS-CoV-2 replication and has similar substrates across mutant coronaviruses, making it an ideal drug target. We synthesized 19 thiazolidinedione derivatives via the Knoevenagel condensations and Mitsunobu reactions as potential 3C-like protease inhibitors. The activity of these inhibitors is screened in vitro by employing the enzymatic screening model of 3C-like protease using fluorescence resonance energy transfer. Dithiothreitol is included in the enzymatic reaction system to avoid non-specific enzymatic inhibition. Active inhibitors with diverse activity are found in this series of compounds, and two representative inhibitors with potent inhibitory activity are highlighted. [ABSTRACT FROM AUTHOR]