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D-glycero-D-manno-Heptose 1,7-bisphosphate (HBP) is the precursor for heptose residues found in Gram-negative bacterial membrane surface glycoproteins and glycolipids. HBP β-anomer was recently reported to be a pathogen-associated molecular pattern (PAMP) that regulates TIFA-dependent immunity. Herein, we report the chemical synthesis of HBP α- and β-anomers, which highlights a C-7 carbon homologation via the Corey-Chaykovsky reaction, and the introduction of a phosphate group at the anomeric position using the Mitsunobu reaction. Furthermore, NF-κB reporter assaying revealed that HBP β-anomer activates the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

A novel amide synthesis methodology is described using amines, CO2 and Grignard reagents and Mitsunobu reagents. The method was applied to carbon-11 radiochemistry to label amides using cyclotron-produced [11C]CO2. The synthetic utility of the one-pot labelling methodology was demonstrated by producing [11C]melatonin. The incorporation of [11C]CO2 into [11C]melatonin was 36% – determined by radioHPLC 2 min post [11C]CO2 delivery. [ABSTRACT FROM AUTHOR]

A convergent synthesis of 5a-carbasugar analogues of the n-Pr-variant of SL0101 is described. The analogues were synthesized in an effort to find compounds with potent in vivo efficacy in the inhibition of p90 ribosomal s6 kinase (RSK1/2). The synthesis derived the desired C-4 L-rhamnose stereochemistry from quinic acid and used a highly selective cuprate addition, NaBH4 reduction, Mitsunobu inversion, and alkene dihydroxylation to install the remaining stereochemistry. A Pd-catalyzed cyclitolization stereoselectively installed the aglycon at the anomeric position. The analogues were evaluated as RSK1/2 inhibitors and found to have 3- to 6-fold improved activity. [ABSTRACT FROM AUTHOR]

Composition of aminolysis products of phenyl glycidyl ether with benzylamine in various conditions was studied. The ratio of 1-(benzylamino)-3-phenoxypropan-2-ol and 1,1'-(benzylazanediyl)bis(3-phenoxypropan-2-ol) does not considerably depend on the nature of the solvent and is basically determined by ratio of initial reagents. 2,6-Bis(phenoxymethyl)morpholine was obtained by dehydration of aminodiol in conditions of Mitsunobu reaction with subsequent reductive debenzylation. [ABSTRACT FROM AUTHOR]

An extensive study of the chemoselective Pd-catalyzed inter- and intramolecular direct C-H arylation of N-benzylated 5-carboxyimidazoles with halides with and without CuI assistance in 1,4-dioxane as a low-polarity solvent was explored. The method was suitable for the synthesis of fused imidazole-based tricyclic systems incorporating medium-sized rings, including, for the first time, eight-membered rings, which are valuable in modern drug design. [ABSTRACT FROM AUTHOR]

A short and efficient protecting group-free synthesis of isotopically labeled 20-[ 18 O]-ingenol has been developed. Based on a highly selective (only one out of four hydroxy groups) Mitsunobu reaction of ingenol with 18 O 2 -acetic acid and subsequent methanolysis, this route yielded the desired 20-[ 18 O]-ingenol in high yield and chemical and isotopic purity. [ABSTRACT FROM AUTHOR]

The molecule of the title keto carbasugar, C7H10O4, is formed by a cyclohexene skeleton with an envelope conformation, substituted by carbonyl, methyl and hydroxyl groups. The crystal structure is controlled mainly by a combination of strong O--H...O and weak C--H...O hydrogen bonds, forming nearly perpendicular chains running parallel to the [110] and [110] directions. This perpendicularity is caused by a tetragonal pseudosymmetry influenced by the similarity between the a and b axes, the value of 90.9770 (10)° of the β angle and the action of a 21 screw axis, which transform each chain into its corresponding nearly orthogonal one. [ABSTRACT FROM AUTHOR]

A simple and efficient synthesis of macrocyclic dilactone tetrahydropyrenophorol has been accomplished from inexpensive and commercially available starting materials. This concise synthesis utilizes regioselective ring opening of epoxide, asymmetric dihydroxylation, and Mitsunobu reaction for the construction of the macrolactone. Graphical abstract: [ABSTRACT FROM AUTHOR]

This research reports the successful asymmetric synthesis of both a 9-hydroxy-5′-methoxy-1,4-benzodioxane framework and a highly functionalised benzofuran scaffold. Both synthetically desirable structures are the result of a Lewis acid catalysed addition of an aryl nucleophile to 1,4-benzodioxane hemiacetals and offer a route towards the synthesis of a number of naturally occurring neolignans. [ABSTRACT FROM AUTHOR]

The total synthesis of four actinoranone stereoisomers led to unambiguous assignment of relative and absolute stereochemistry of the natural product. Key features of the convergent, fully stereocontrolled route include the use of a Negishi carbozirconation/iodination, a Friedel-Crafts cyclization, a Felkin-controlled addition reaction, a Mitsunobu reaction, and a late-stage C−H oxidation. [ABSTRACT FROM AUTHOR]

Reported is an efficient synthesis of adenyl and uridyl 5′-tetrachlorophthalimido-5′-deoxyribonucleosides, and guanylyl 5′-azido-5′-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5′-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5′-hydroxyl with an azido group. The resulting compounds were converted to 5′-amino-5′-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2′,3′-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5′-tetrachlorophthalimido and 5′-azido demonstrated increased antibacterial effect. [ABSTRACT FROM PUBLISHER]

This research reports the successful asymmetric synthesis of both a 9-hydroxy-5'-methoxy-1,4-benzodioxane framework and a highly functionalised benzofuran scaffold. Both synthetically desirable structures are the result of a Lewis acid catalysed addition of an aryl nucleophile to 1,4-benzodioxane hemiacetals and offer a route towards the synthesis of a number of naturally occurring neolignans. [ABSTRACT FROM AUTHOR]

The 2-arylcyclopropylamine (ACPA) motif is often seen in biologically active compounds. This review focuses on the synthesis of biologically active ACPAs and categorizes, by reaction type, the synthetic methods used toward such compounds. Introduction Cyclopropanation Using Diazo Compounds Styrene Cinnamate Vinyl Phthalimide Vinyl Acetamide Oxazolone Diketopiperazine Cyclopropanation Using Ylides Cinnamate Nitrostyrene Oxirane Nitroacetate Transformation of Cyclopropanes Iodocyclopropane Aminocyclopropane Miscellaneous Methods Kulinkovich Reaction Three-Component Reaction Intramolecular Nucleophilic Cyclization Intramolecular Mitsunobu Reaction Rearrangement from Cyclobutanone Summary. [ABSTRACT FROM AUTHOR]

Title compound was designed to be a black quencher of pyrene fluorescence. It was made amphiphilic to serve as a membrane-bound probe. The synthesis is a two-step procedure. The first step is a Mitsunobu reaction of [{(phenyldiazenyl)phenyl}diazenyl]phenol with 1,2-O-isopropylideneglycerol. The second step is the cleavage of the isopropylidene protecting group. The title compound has the extinction coefficient 59,000 at λmax = 380 nm. The Forster distance between the title compound and the pyrene was found to be 37.8 Å. [ABSTRACT FROM AUTHOR]

This work reports the gas separation properties of polyimides (PIs) with different chemical structures, designed for the removal of carbon dioxide from flue gases. To study the effect of a backbone structure on gas permeability and selectivity, three different methods of chemical modification of the poly (hydroxyimide) (PIOH) were applied. The introduction of bulky pendant groups in a PI chain was accomplished by Mitsunobu reaction; conversion of PIOH to polybenzoxazole rigid structure (PITR) was performed by thermal cyclization in an inert atmosphere, whereas incorporation of CO2 -philic polyoxyethylene (PEO) segments into main chain was carried out at the polycondensation stage by using a mixture of aromatic and PEO-based diamines. The modified polymers were characterized by nuclear magnetic resonance (1H NMR) and fourier transform infrared (FTIR) spectroscopies, and thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) techniques. It was found that the performed modifications resulted in membrane materials with significantly improved gas permeability and either maintained or even improved CO2 /N2 selectivity. [ABSTRACT FROM AUTHOR]

We revealed intramolecular oxidative arylations in 7-azaindoles and pyrroles that, for the first time, provided direct access to 7-azaindole- or pyrrole-fused isoindolines and tetrahydroisoquinolines. In addition, N-benzylation of 7-azaindoles or pyrroles with sterically hindered sec-benzyl alcohols by Mitsunobu reaction followed by intramolecular oxidative arylation allowed access to chiral congeners of fused isoindolines that have little precedence. A new opportunity in the design and synthesis of fluorene-based organic emitters is demonstrated in the preparation of novel fused N-heterocycle tethered fluorenes, including a chiral fluorene architecture. [ABSTRACT FROM AUTHOR]

An efficient oxidation-reduction condensation reaction of diazaphosphites with various nonacidic pronucleophiles in the presence of DIAD as a weak oxidant has been developed for carbon-heteroatom bond formation. This mild process affords structurally diverse tertiary amines, secondary amines, esters, ethers, and thioethers in moderate to excellent yields. The selective synthesis of secondary amines from primary amines has been achieved. Importantly, a practical application to the synthesis of antiparkinsonian agent piribedil has been demonstrated. [ABSTRACT FROM AUTHOR]

Palladium catalyzed intramolecular aminoacetoxylation of d -ribose derived alkenyl tosylsulfonamide to deliver l -deoxyallonojirimycin in an overall yield of 19%. The preliminary screening of l -deoxyallonojirimycin against carbohydrate processing enzymes showed moderate inhibitory activity against α-glucosidase (yeast) and α-mannosidases. [ABSTRACT FROM AUTHOR]

A convergent three-step method for the synthesis of 2-substituted chromans is described. These results have been accomplished via the Heck coupling of readily accessible allylic alcohols and 2-iodophenols, followed by reduction and Mitsunobu cyclization. The utility and generality of this method is demonstrated through the synthesis of a series of 2-aryl-, 2-heteroaryl- and 2-alkylchromans, as well as an azachroman derivative. The asymmetric version of this approach via a Noyori-catalyzed ketone reduction and subsequent cyclization is likewise highlighted. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel ring contraction reaction of 4,5-disubstituted 1,2-dithianes is discovered. • The 3,4-disubstituted 1,2 dithiolanes products are formed stereoselectively. • Mitsunobu reaction conditions are used with overall retention of configuration. • Representative examples of O , N , and S nucleophiles are demonstrated. • S-episulfonium intermediates are postulated. Monobenzoylated 1,2-dithiane-4,5 diols undergo a novel ring contraction reaction under Mitsunobu conditions to produce 3,4-disubstituted 1,2-dithiolanes. This transformation is stereoselective and proceeds with retention of configuration. The yields for the trans isomers are higher than those of the cis series for a variety of O , N and S nucleophiles. A plausible pathway for forming the 1,2-dithiolanes involves the formation of a S-episulfonium intermediates. [ABSTRACT FROM AUTHOR]

• The chiral 1-hydroxy-cyclopentenyl analogs (22a - b) were synthesized in the multi-gram scale from D-ribose. • New N 7 -/ N 9 -2,6-dihalo-3-deazaneplanocin and N 7 -6-azido-3-deazaneplanocin analogs were prepared. • Novel N 9 -2,6-dibromo-3-deazaneplanocin (44a) exhibited the most potent activity against flu a (H1N1) with EC 50 value of 7.0 μM in vitro. 3-Deazaneplanosin A (DZNep, 2) analogs showed a broad spectrum of biological activity against some cancers and DNA/RNA viruses as a promising inhibitor of the S-adenosyl- L -homocysteine (SAH) hydrolase and the enhancer of zeste homolog 2 (EZH2). Recently, 3-halogenated DZNep analogs were reported as potent inhibitors against RNA viruses as an inhibitor of SAH hydrolase, but 6-halogenated DZNep and its analogs was not studied as an antiviral agent to date. Thus, N 9 -/ N 7 -2,6-dihalo-DZNep and N 7 -6-amino/azido-DZNep analogs were prepared using Mitsunobu reaction of 3-deazapurine derivatives with chiral cyclopentene-1-ol derivatives (22a - b). With a modified procedure of a previous synthetic method, the chiral 22a and 22b were prepared in 50% overall yield from D -ribose. Additionally, 3-deazapurine analogs including 2,6-dibromo-3-deazapurine 30a , 2,6 - dichloro-3-deazapurine 30b , 6-azido-3-deazapurine 36 , N 6-Bz-3-deazapurine 38a , and N 6 , N 6-bisBz-3-deazapurine 38b were synthesized in 25–43% overall yields. Mitsunobu reaction of 30a - b with 22a afforded a mixture of N 7 -/ N 9 -isomer in the ratio of 4:5 and 1:1, respectively. The reaction of 36 and 38a with 22a provided their corresponding only N 7 -isomer products, whereas N 6 , N 6-bisBz-3-deazapurine (38b) gave single N 9 -isomer as a regioselective product. Among prepared DZNep analogs, novel N 9 -2,6-dibromo-3-deazaneplanocin (44a) exhibited the most potent activity (EC 50 7.0 μM) against Flu A (H1N1) with CC 50 >100 in vitro. Unexpectedly, N 7 -6-azido-3-deazaneplanocin (46) displayed EC 50 22.5 μM, and 25.3 μM against Flu A (H1N1) and (H3N2) with CC 50 >100, respectively. The other 3-DZNep analogs showed no significant antiviral potency against Flu A and B in vitro and against dengue virus-2 replicon. Currently, N 9 -2,6-dibromo-3-deazaneplanocin (44a) was found as a new heat compound for Flu A (H1N1). [Display omitted] [ABSTRACT FROM AUTHOR]

Narwedine, an immediate precursor to the therapeutically valuable alkaloid (-)-galanthamine, has been synthesised by engaging an iodinated isovanillin derivative in an intermolecular Mitsunobu reaction with a 2-cyclohexen-1-ol derivative. The resulting aryl ether participated in an exceptionally efficient intramolecular Heck reaction to give a tetracyclic lactol after the hydrolysis of the primary cyclisation product. This last compound is an advanced intermediate associated with the Magnus synthesis of narwedine and could be elaborated to narwedine itself under reductive amination conditions. As a result, an eleven-step synthesis of galanthamine has been established. [ABSTRACT FROM AUTHOR]

inexpensive benzyl L-lactate, the configuration of which was inverted by a Mitsunobu reaction with trifluoroacetate. The resulting benzyl D-lactate was cyclised by a domino addition-Wittig alkenation reaction with Ph3PCCO. The product tetronic acid was acylated with a second equivalent of this ylide to give a 3-acylylidenetetronic acid, which was olefinated directly with tert-butyl glyoxylate. The product alkene was hydrogenated and deprotected to afford pure crystalline (R)-(+)-carolinic acid, which proved inactive against Staphylococcus aureus and Escherichia coli mutant D21f2. [ABSTRACT FROM AUTHOR]

The synthesis of a series of new alkylsulfanyl phthalazinone and phthalazine derivatives is described. The target compounds were efficiently synthesized in a four step sequence, consisting of (1) cyclization of 2-formylbenzoic acid with hydrazine hydrate to form phthalazinone, (2) the direct bromination of phthalazinone core with KBr 3 , (3) alkylation of the obtained 4-bromolactam (Mitsunobu procedure) to make N - and also O -alkyl derivatives and finally (4) palladium-catalyzed coupling reactions of 2-alkyl-4-bromophthalazinone and 1-alkyloxy-4-bromophthalazine derivatives with aliphatic mercaptanes. Furthermore, the synthesis of 2-methyl-8-(propan-2-yl)sulfanyl-pyrido[3,4- d ]pyridazin-1(2 H )-one from 2-methyl-pyrido[3,4- d ]pyridazin-1(2 H )-one via bromination reaction with KBr 3 and subsequent sulfanylation by isopropyl mercaptan under catalyzed coupling reaction conditions is also described. [ABSTRACT FROM AUTHOR]

A Mitsunobu approach for the synthesis of sulfinate esters by direct nucleophilic substitution of alcohols is described. The salient features of this strategy include neutral and metal-free conditions for the rapid synthesis of sulfinates in high yields. The present protocol using p-toluenesulfonylmethyl isocyanide (TosMIC) and the triphenylphosphine (TPP)/diisopropyl azodicarboxylate (DIAD) reagent system represents the general synthetic route to this important class of compounds. [ABSTRACT FROM AUTHOR]

The synthesis of six-, seven-, and eight-membered cis-dihydroxy azacycles has been accomplished from D-ribose using Vasella reductive amination as a key step and utilization of hydroboration-oxidation, Mitsunobu reaction, and ring-closing metathesis (RCM) reactions in a facile manner. These homologous dihydroxylated heterocyclic scaffolds were subjected to the glycosidase inhibition assays. However, only a moderate inhibitory activity for three out of five compounds was observed against α-glucosidases with a high degree of selectivity. [ABSTRACT FROM AUTHOR]

Total synthesis of (3R, 4 S)‐4‐Hydroxylasiodiplodin has been accomplished through convergent strategy using D‐isoascorbic acid and trihydroxybenzoic acid as the starting materials in an optimal reaction sequence. The salient features of the synthesis are the utilization of Stille coupling, trans‐esterification and Ring‐Closing Metathesis (RCM). [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Developed a scalable synthetic route to cladosporin, a potent antimalarial natural product. • Mitsunobu inversion and carbon monoxide insertion are the key steps of the present synthesis. • The target natural product cladosporin has been synthesized in gram scale for the first time. Abstract Cladosporin, a secondary metabolite isolated from fungal sources like Cladosporium cladosporioides and Aspergillus flavus was found to exhibit selective nano-molar activity against malarial parasite Plasmodium falciparum by inhibiting parasitic protein biosynthesis. In addition, this natural product has a broad range of bioactivities including, antiparasitic, antifungal, antibacterial as well as plant growth inhibition. However, it has limited availability from the natural sources for further development. Herein, we report a modified and improved synthetic route which led us to produce this potent natural product in a gram scale. Conversion of the undesired diastereomer to desired one via Mitsunobu inversion of secondary alcohol and carbon monoxide insertion reaction towards the construction of isocoumarin unit are the key features of the present synthesis. [ABSTRACT FROM AUTHOR]

The synthesis and study of steroids and terpenes continues to be a topic of widespread interest, the esterification and etherification under Mitsunobu conditions of primary alcohol such as geraniol prepared in 95% yield, and when a chiral secondary alcohol such as cholesterol or menthol is used, sufficient configurational inversion of alcohol with 65% yield, but the reaction of tertiary alcohols the α-terpeniol for example are rare.