Free Hydroxy Research Articles

Enhancing Ru(II)-Catalysis with Visible-Light-Mediated Dye-Sensitized TiO2 Photocatalysis for Oxidative C-H Olefination of Arene Carboxylic Acids at Room Temperature.

Erythrosine B sensitized TiO2 photocatalysis has been combined with Ru(II)-catalysis to accomplish an oxidative olefination/annulation of benzoic acids with activated olefins under mild conditions that tolerates useful functionalities, such as halides, free hydroxy, acetamido, etc. The morphology of the photocatalyst is unaffected during the reaction and it can be reused. Mechanistic studies favor the involvement of a photo-induced single electron transfer process.

DETAILS OF A MULTICOMPONENT BIGINELLI REACTION INVOLVING 3-OXOBUTANOYL-CONTAINING PODANDS, AROMATIC ALDEHYDES, AND 1,2,4-TRIAZOLE-3-AMINE

A reaction of 3-oxobutanoyl-containing podands with thiophene-2-carbaldehyde (or benzaldehyde) and 3-amino-1,2,4-triazole gave podands featuring a 4,7-dihydro[1,2,4]triazolo[1,5- а ]pyrimidine motif. It was established that the process was accompanied by the formation of [4,3- а ]-isomers, which occurred in a slight excess during the synthesis of a podand containing a phenyl group at position 7 and, on the other hand, were observed as the minor products during the synthesis of podands bearing a thiophen-2-yl substituent. Trace amounts of monosubstituted podands were also detected, containing a free hydroxy group along with the triazolodihydropyrimidine pharmacophore.

Nostotrebin 6 Related Cyclopentenediones and δ-Lactones with Broad Activity Spectrum Isolated from the Cultivation Medium of the Cyanobacterium Nostoc sp. CBT1153

Cyanobacteria are an interesting source of biologically active natural products, especially chemically diverse and potent protease inhibitors. On our search for inhibitors of the trypanosomal cysteine protease rhodesain, we identified the homodimeric cyclopentenedione (CPD) nostotrebin 6 (1) and new related monomeric, dimeric, and higher oligomeric compounds as the active substances in the medium extract of Nostoc sp. CBT1153. The oligomeric compounds are composed of two core monomeric structures, a trisubstituted CPD or a trisubstituted unsaturated δ-lactone. Nostotrebin 6 thus far has been the only known cyanobacterial CPD. It has been found to be active in a broad variety of assays, indicating that it might be a pan-assay interference compound (PAIN). Thus, we compared the antibacterial and cytotoxic activities as well as the rhodesain inhibition of selected compounds. Because a compound with a δ-lactone instead of a CPD core structure was equally active as nostotrebin 6, the bioactivities of these compounds seem to be based on the phenolic substructures rather than the CPD moiety. While the dimers were roughly equally potent, the monomer displayed slightly weaker activity, suggesting that the compounds show unspecific activity depending upon the number of free phenolic hydroxy groups per molecule.

Features of a multicomponent Biginelli reaction involving 3-oxobutanoyl-containing podands, aromatic aldehydes, and 1,2,4-triazol-3-amine

A reaction of 3-oxobutanoyl-containing podands with thiophene-2-carbaldehyde (or benzaldehyde) and 3-amino-1,2,4-triazole gave podands featuring a 4,7-dihydro[1,2,4]triazolo[1,5-а]pyrimidine motif. It was established that the process was accompanied by the formation of [4,3-а]-isomers, which occurred in a slight excess during the synthesis of a podand containing a phenyl group at position 7 and, on the other hand, were observed as the minor products during the synthesis of podands bearing a thiophen-2-yl substituent. Trace amounts of monosubstituted podands were also detected, containing a free hydroxy group along with the triazolodihydropyrimidine pharmacophore.

Probing the Interconversion of Labdane Lactones from the Chinese Liverwort Pallavicinia ambigua.

We report on the spontaneous, reversible intramolecular transesterification of natural labdane lactones. Through extensive spectroscopic analysis, the interconversion between the two tautomers was investigated, which could be retarded when the free hydroxy group was acetylated or the exocyclic double bond of the lactone ring was mutated. Besides, a conversion mechanism was postulated, and the energy barriers were calculated by density functional theory calculations. Furthermore, the tautomers were found to inhibit the virulence of the efflux pump-deficient Candida albicans DSY654.

A Coumarin Triflate Reagent Enables One-Step Synthesis of Photo-Caged Lipid Metabolites for Studying Cell Signaling.

Photorelease of caged compounds is among the most powerful experimental approaches for studying cellular functions on fast timescales. However, its full potential has yet to be exploited, as the number of caged small molecules available for cell biological studies has been limited by synthetic challenges. Addressing this problem, a straightforward, one‐step procedure for efficiently synthesizing caged compounds was developed. An in situ generated benzylic coumarin triflate reagent was used to specifically functionalize carboxylate and phosphate moieties in the presence of free hydroxy groups, generating various caged lipid metabolites, including a number of GPCR ligands. By combining the photo‐caged ligands with the respective receptors, an easily implementable experimental platform for the optical control and analysis of GPCR‐mediated signal transduction in living cells was developed. Ultimately, the described synthetic strategy allows rapid generation of photo‐caged small molecules and thus greatly facilitates the analysis of their biological roles in live cell microscopy assays.

Characterization of alkaline phosphatase PhoK from Sphingomonas sp. BSAR-1 for phosphate monoester synthesis and hydrolysis

The biocatalytic activity of a so far underexploited alkaline phosphatase, PhoK from Sphingomonas sp. BSAR-1, was extensively studied in transphosphorylation and hydrolysis reactions. The use of high-energy phosphate donors and oligophosphates as suitable phosphate donors was evaluated, as well as the hydrolytic activity on a variety of phosphate monoesters. While substrates bearing free hydroxy group displayed only moderate reactivity as acceptors for transphosphorylation by PhoK, strong hydrolytic activity on a broad variety of phosphate monoesters under alkaline conditions was observed. Site-directed mutagenesis of selected amino acid residues in the active site provided valuable insights on their involvement in enzyme catalysis. The key residue Thr89 so far postulated to engage in enzyme phosphorylation was confirmed to be crucial for catalysis and could be replaced by serine, albeit with much lower catalytic efficiency.

Tough thermosetting polyurethanes and adhesives from rubber seed oil by hydroformylation

ABSTRACTRubber seed oil (RSO), extracted from the seeds of rubber trees, is inedible oil with high free fatty acid content. In order to add value to RSO, we prepared a polyol with primary OH groups via hydroformylation/hydrogenation. Free hydroxy fatty acids formed in the process were utilized as reactive diluents, viscosity reducers, and adhesion promoters through hydrogen bonding with the substrate. The structures of the oil and polyol were analyzed using a range of analytical methods. The polyol had a hydroxyl number of 244 mg KOH g−1 and an acid number of 21 mg KOH g−1. The polyurethane prepared from this polyol and diphenylmethane diisocyanate was a highly crosslinked, tough material with a glass transition at 44 °C, high tensile strength and elongation, and attractive electrical properties. When used as a wood adhesive, it displayed extraordinary shear strength characterized by substrate wood failure rather than cohesive failure of the polymer. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48509.

Phenylpropanoid glycosides from the fruit of Lycium barbarum L. and their bioactivity

Fifteen phenylpropanoid glycosides, including six undescribed compounds were isolated from the fruit of Lycium barbarum L. (Solanaceae) (goji or wolfberry). Their structures were identified by detailed spectroscopic analyses. Seven known compounds were firstly isolated from the genus Lycium, in which the 1D and 2D NMR data of one compound were reported for the first time. Notably, two undescribed compounds were a pair of rare tautomeric glycoside anomers characterized by the presence of free anomeric hydroxy. Antioxidant and hypoglycemic activities of all these compounds were assessed using DPPH radical scavenging, oxygen radical absorbance capacity (ORAC), and α-glucosidase inhibitory assays, respectively. These compounds showed different levels of oxygen radical absorbance capacity, and some isolates exhibited potent antioxidant activity with greater ORAC values than the positive control (EGCG).

Chemoenzymatic synthesis of hydroxytyrosol monoesters and their suppression effect on nitric oxide production stimulated by lipopolysaccharides.

Fatty acid monoesters of hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol] were synthesized in two steps from tyrosol (4-hydroxyphenylethanol) by successive Candida antarctica lipase B-catalyzed chemoselective acylation on the primary aliphatic hydroxy group over phenolic hydroxy group in tyrosol, and 2-iodoxybenzoic acid (IBX)-mediated hydroxylation adjacent to the remaining free phenolic hydroxy group. Examination of their suppression effects on nitric oxide production stimulated by lipopolysaccharides in RAW264.7 cells showed that hydroxytyrosol butyrate exhibited the highest inhibition (IC50 7.0 μM) among the tested compounds.

Impact of Acetylated and Non-Acetylated Fucose Analogues on IgG Glycosylation.

The biological activity of therapeutic antibodies is highly influenced by their glycosylation profile. A valuable method for increasing the cytotoxic efficacy of antibodies, which are used, for example, in cancer treatment, is the reduction of core fucosylation, as this enhances the elimination of target cells through antibody-dependent cell-mediated cytotoxicity. Development of fucose analogues is currently the most promising strategy to reduce core fucosylation without cell line engineering. Since peracetylated sugars display enhanced cell permeability over the highly polar free hydroxy sugars, this work sought to compare the efficacy of peracetylated sugars to their unprotected forms. Two potent fucose analogues, 2-deoxy-2-fluorofucose and 5-alkynylfucose, and their acetylated forms were compared for their effects on fucosylation. 5-alkynylfucose proved to be more potent than 2-deoxy-2-fluorofucose at reducing core fucosylation but was associated with a significant higher incorporation of the alkynylated fucose analogue. Acetylation of the sugar yielded only slightly lower fucosylation levels suggesting that acetylation has a minor impact on cellular entry. Even though the efficacy of all tested components was confirmed, results presented in this study also show a significant incorporation of unnatural fucose analogues into the glycosylation pattern of the produced IgG, with unknown effect on safety and potency of the monoclonal antibody.

Nonenzymatic sensing of hydrogen peroxide using a glassy carbon electrode modified with graphene oxide, a polyamidoamine dendrimer, and with polyaniline deposited by the Fenton reaction.

A highly sensitive electrochemical sensor is described for the determination of H2O2. It is based on based on the use of polyaniline that was generated in-situ and within 1min on a glassy carbon electrode (GCE) with the aid of the Fe(II)/H2O2 system. Initially, a 2-dimensional composite was prepared from graphene oxide and polyamidoamine dendrimer through covalent interaction. It was employed as a carrier for Fe(II) ions. Then, the nanocomposite was drop-coated onto the surface of the GCE. When exposed to H2O2, the Fe(II) on the GCE is converted to Fe(III), and free hydroxy radicals are formed. The Fe(III) ions and the hydroxy radicals catalyze the oxidation of aniline to produce electroactive polyaniline on the GCE. The resulting sensor, best operated at a working potential as low as 50mV (vs. SCE) which excludes interference by dissolved oxygen, has a linear response in the 500nM to 2mM H2O2 concentration range, and the detection limit is 180nM. The sensor was successfully applied to the determination of H2O2 in spiked milk and fetal bovine serum samples. Graphical abstract Schematic presentation of a sensitive electrochemical sensor employed for detection of H2O2 in sophisticated matrices by using graphene oxide-PAMAM dendrimer as initiator container and Fe2+/H2O2 system as signal enhancer.

Synthesis and structure of functionalized podands containing 4,7-dihydrotetrazolo[1,5-а]pyrimidine ring. Differently substituted dihydropyrimidine podands

The reaction of 3-oxobutanoate-containing polyethers with benzaldehyde and 5-aminotetrazole in the presence of polyphosphoric acid was used to synthesize podands containing two terminal tetrazolo[1,5-а]dihydropyrimidine groups. Byproducts were isolated and identified as podands containing different substituents – one 4,7-dihydrotetrazolo[1,5-а]pyrimidine ring system and a free hydroxy group at the other terminus of the polyether chain. Analogous differently substituted podands, including one 3,4-dihydropyrimidine-2(1H)-thione moiety, were isolated from the reactions of 3-oxobutanoate-containing polyethers with benzaldehyde and thiourea.

A Ring Contraction of 2,3-Di- O-Silylated Thiopyranosides To Give Thiofuranosides under Mildly Acidic Conditions.

A pyranose ring contraction of ethyl 1-thio-β-d-galactopyranosides has been discovered that proceeds with retention of aglyconunder mildly acidic conditions (aq TFA in CH2Cl2). Key factors for success of this rearrangement are the presence of bulky silyl (TIPS or TBDPS) substituents at both O-2 and O-3 and a free hydroxy group at C-4 (derivatives with acid-labile protective groups at O-4 will also engage in this reaction). The rearrangement cleanly proceeds for 2,3-di- O-TIPS derivatives with two hydroxy groups at C-4 and C-6, acid-labile TES groups at O-4 and O-6, or one acyl substituent (Bz, ClAc) at O-6. A possibility to switch the direction of the debenzylidenation reaction in 4,6- O-benzylidene-2,3-di- O-TIPS/TBDPS derivatives by the choice of an acid (TFA, which cleanly gives furanose, versus AcOH, which cleaves benzylidene acetal only) may present an advantage in the divergent synthesis of selectively protected glycosyl donors (either in furanose or pyranose form) useful for the synthesis of biologically important oligosaccharides.

An Organocatalytic Asymmetric Synthesis of Chiral β,β-Diaryl-α-amino Acids via Addition of Azlactones to In Situ Generated para-Quinone Methides.

An organocatalytic intermolecular C-C bond formation process leading to the efficient synthesis of chiral β,β-diaryl-α-amino acid derivatives is described. In the presence of a suitable chiral phosphoric acid catalyst, a range of para-hydroxybenzyl alcohols serve as efficient precursors to para-quinone methides and then react with azlactones in 1,6-conjugate addition reactions. The asymmetric control has been carefully optimized together with diastereocontrol enabled by identification of the reversible feature of the C-C bond formation and subsequent inhibition by protection of the free hydroxy group in one pot. Compared with previous approaches, including those with pre-synthesized para-quinone methides, this protocol provides an alternative and complementary step- and pot-economical approach for the synthesis of chiral β,β-diaryl-α-amino acid derivatives.

Stereoretentive Reactions at the Anomeric Position: Synthesis of Selenoglycosides.

Reported is the stereospecific cross-coupling of anomeric stannanes with symmetrical diselenides, resulting in the synthesis of selenoglycosides with exclusive anomeric control. The reaction proceeds without the need for directing groups and is compatible with free hydroxy groups as demonstrated in the preparation of glycoconjugates derived from mono-, di-, and trisaccharides and peptides (35 examples). Given its generality and broad substrate scope, the glycosyl cross-coupling method presented herein can find use in the synthesis of selenium-containing glycomimetics and glycoconjugates.

Stereoretentive Reactions at the Anomeric Position: Synthesis of Selenoglycosides

AbstractReported is the stereospecific cross‐coupling of anomeric stannanes with symmetrical diselenides, resulting in the synthesis of selenoglycosides with exclusive anomeric control. The reaction proceeds without the need for directing groups and is compatible with free hydroxy groups as demonstrated in the preparation of glycoconjugates derived from mono‐, di‐, and trisaccharides and peptides (35 examples). Given its generality and broad substrate scope, the glycosyl cross‐coupling method presented herein can find use in the synthesis of selenium‐containing glycomimetics and glycoconjugates.

Substrate Directed Asymmetric Reactions.

Historically, reagent controlled reactions (mechanism controlled reactions) have played a significant role in the asymmetric synthesis of complex structures. In contrast, today's asymmetric synthesis is greatly dependent on substrate directed approaches. In this approach, a polar functional group, namely, a "directing group", in the vicinity of the reactive site inside the substrate has been documented to preassociate with the chiral catalyst, which exerts stereodirecting influence by directing the reacting partner toward one of the enantiotopic faces of the reaction center. Those reactions usually proceed through exceptionally ordered transition states and result in extraordinary levels of stereoselection. Within the last four decades, the substrate directed approach has become an indispensible tool for the preparation of complex chiral frameworks starting directly from relatively simple achiral substrate molecules via asymmetric induction or various resolution techniques or both. Likewise, the substrate directed approach has been applied to functionalize enantiopure substrates bearing pre-exisiting stereocenters into complex structures as a single diastereomer. A classical example is Sharpless asymmetric epoxidation of allylic alcohols in which the free hydroxy function acts as an active anchor to a dimeric Ti-catalyst that controls the stereochemical outcome of the epoxidation process by transferring the oxidant enantioselectively. The principal aim of the present review is to give a general overview of substrate directed asymmetric transformations, a topic that has not yet been documented in the form of a concise review of recently developed approaches. Due to the large number of related applications, only recent advances that have been documented within the last two decades have been reviewed. Furthermore, in the current review, we have mainly highlighted asymmetric reactions that are controlled by abundant and frequently used directing groups such as hydroxy, amide, and sulfonamide groups. In addition, selected examples of a few important substrate-directed chemo-, regio-, and diastereoselective reactions have also been included in this review.

Early/Late Heterobimetallic Tantalum/Rhodium Species Assembled Through a Novel Bifunctional NHC-OH Ligand.

The straightforward synthesis of a new unsymmetrical hydroxy-tethered N-heterocyclic carbene (NHC) ligand, HL, is presented. The free ligand exhibits an unusual OH-carbene hydrogen-bonding interaction. This OH-carbene motif was used to yield 1) the first tantalum complex displaying both a Fischer- and Schrock-type carbene ligand and 2) a unique NHC-based early/late heterobimetallic complex. More specifically, the protonolysis chemistry between the ligand's hydroxy group and imido-alkyl or alkylidene-alkyl tantalum precursor complexes yielded the rare monometallic tantalum-NHC complexes [Ta(XtBu)(L)(CH2 tBu)2 ] (X=N, CH), in which the alkoxy-carbene ligand acts as a chelate. In contrast, HL only binds to rhodium through the NHC unit in [Rh(HL)(cod)Cl] (cod=cycloocta-1,5-diene), the hydroxy pendant arm remaining unbound. This bifunctional ligand scaffold successfully promoted the assembly of rhodium/tantalum heterobimetallic complexes upon either 1) the insertion of [Rh(cod)Cl]2 into the Ta-NHC bond in [Ta(NtBu)(L)(CH2 tBu)2 ] or 2) protonolysis between the free hydroxy group in [Rh(HL)(cod)Cl] and one alkyl group in [Ta(NtBu)(CH2 tBu)3 ].

Transition-Metal-Free C-S Bond Formation: Synthesis of Polysubstituted Diaryl Sulfides and α-Thioarylcarbonyl Compounds.

A transition-metal-free protocol for the construction of C-S bonds has been developed. Acetylacetone acts as a new and green aryl source for the synthesis of polysubstituted diarylsulfides bearing a free hydroxy group and a ketone group, which provides a new access to a series of flavonoids containing a thioaryl group. In addition, a series of α-thioarylcarbonyl compounds are obtained in good to excellent yields.