Indium-Mediated Acyloxyallylation-Based Synthesis of -Configured Higher-Carbon Sugar Alcohols as Potential Phase Change Materials.

Sugar alcohols fulfilling specific structural requirements are a substance class with great potential as organic phase change materials (PCMs). Within this work, we demonstrate the indium-mediated acyloxyallylation (IMA) as a useful strategy for the synthesis of higher-carbon sugar alcohols of the -family featuring all hydroxyl groups in a 1,3--relationship with three major synthetic achievements: first, the dihydroxylation of the IMA-derived allylic sugar derivates was systematically studied in terms of diastereoselectivity, revealing a high degree of substrate control toward -addition. Second, we demonstrated the use of a "double Mitsunobu" reaction, inverting the stereochemistry of terminal diols.

Phytosiderophore pathway response in barley exposed to iron, zinc or copper starvation.

Efficient micronutrient acquisition is a critical factor in selecting micronutrient dense crops for human consumption. Enhanced exudation and re-uptake of metal chelators, so-called phytosiderophores, by roots of graminaceous plants has been implicated in efficient micronutrient acquisition. We compared PS biosynthesis and exudation as a response mechanism to either Fe, Zn or Cu starvation.

Total synthesis of [ C ]-labeled phytosiderophores of the mugineic and avenic acid families.

We, herein, report the synthesis of C -labeled natural products from the mugineic acid and avenic acid family. These phytosiderophores ("plant iron carriers") are built up from non-proteinogenic amino acids and play a key role in micronutrient uptake in gramineous plants. In this work, two central building blocks are prepared from labeled starting materials ( C -bromoacetic acid, C -glycine) and further employed in our recently reported divergent, branched synthetic strategy delivering eight isotopically labeled phytosiderophores.

Surveying the mugineic acid family: Ion mobility - quadrupole time-of-flight mass spectrometry (IM-QTOFMS) characterization and tandem mass spectrometry (LC-ESI-MS/MS) quantification of all eight naturally occurring phytosiderophores.

Phytosiderophores (PS) are root exudates released by grass species (Poaceae) that play a pivotal role in iron (Fe) plant nutrition. A direct determination of PS in biological samples is of paramount importance in understanding micronutrient acquisition mediated by PS. To date, eight plant-born PS have been identified; however, no analytical procedure is currently available to quantify all eight PS simultaneously with high analytical confidence.

An Organic Chemist's Guide to Mediated Laccase Oxidation.

Laccases are oxidases that only require O as a terminal oxidant. Thus, they provide an attractive green alternative to established alcohol oxidation protocols. However, laccases typically require catalytic amounts of mediator molecules to serve as electron shuttles between the enzyme and desired substrate.

Sterically Demanding Flexible Phosphoric Acids for Constructing Efficient and Multi-Purpose Asymmetric Organocatalysts.

Herein, we present a novel approach for various asymmetric transformations of cyclic enones. The combination of readily accessible chiral diamines and sterically demanding flexible phosphoric acids resulted in a simple and highly tunable catalyst framework. The careful optimization of the catalyst components led to the identification of a particularly powerful and multi-purpose organocatalyst, which was successfully applied for asymmetric epoxidations, aziridinations, aza-Michael-initiated cyclizations, as well as for a novel Robinson-like Michael-initiated ring closure/aldol cyclization.

Sterically Demanding Flexible Phosphoric Acids for Constructing Efficient and Multi-Purpose Asymmetric Organocatalysts.

Herein, we present a novel approach for various asymmetric transformations of cyclic enones. The combination of readily accessible chiral diamines and sterically demanding flexible phosphoric acids resulted in a simple and highly tunable catalyst framework. The careful optimization of the catalyst components led to the identification of a particularly powerful and multi-purpose organocatalyst, which was successfully applied for asymmetric epoxidations, aziridinations, aza-Michael-initiated cyclizations, as well as for a novel Robinson-like Michael-initiated ring closure/aldol cyclization.

A Kinetic Photometric Assay for the Quantification of the Open-Chain Content of Aldoses.

Aldoses exist predominantly in the cyclic hemiacetal form, which is in equilibrium with the open-chain aldehyde form. The small aldehyde content hampers reactivity when chemistry addresses the carbonyl moiety. This low concentration of the available aldehyde is generally difficult to ascertain.

A Unified Approach to Phytosiderophore Natural Products.

This work reports on the concise total synthesis of eight natural products of the mugineic acid and avenic acid families (phytosiderophores). An innovative "east-to-west" assembly of the trimeric products resulted in a high degree of divergence enabling the formation of the final products in just 10 or 11 steps each with a minimum of overall synthetic effort. Chiral pool starting materials (l-malic acid, threonines) were employed for the outer building blocks while the middle building blocks were accessed by diastereo- and enantioselective methods.

Straight Forward and Versatile Differentiation of the l- and d--d- Heptose Scaffold.

Bacterial lipopolysaccharides (LPS) are important bio-medical structures, playing a major role in the interaction with human immune systems. Their core regions, containing multiple units of l--d- heptoses (l,d-heptose), are highly conserved structurally (with 3 and 7 glycosidic bonds), making them an epitope of high interest for the potential development of new antibiotics and vaccines. Research in this field has always been restricted by the limited availability of the parent l,d-heptose as well as its biochemical epimeric precursor d--d- heptose (d,d-heptose).

Intercepted dehomologation of aldoses by N-heterocyclic carbene catalysis - a novel transformation in carbohydrate chemistry.

The development of an N-heterocyclic carbene (NHC) catalysed intercepted dehomologation of aldoses is reported. The unique selectivity of NHCs for aldehydes is exploited in the complex context of reducing sugars. Examples of strong substrate governance for either intercepted dehomologation or a subsequent redox-lactonisation were identified and mechanistically understood.

A marine bacterial enzymatic cascade degrades the algal polysaccharide ulvan.

Marine seaweeds increasingly grow into extensive algal blooms, which are detrimental to coastal ecosystems, tourism and aquaculture. However, algal biomass is also emerging as a sustainable raw material for the bioeconomy. The potential exploitation of algae is hindered by our limited knowledge of the microbial pathways-and hence the distinct biochemical functions of the enzymes involved-that convert algal polysaccharides into oligo- and monosaccharides.

Methyl glycosides via Fischer glycosylation: translation from batch microwave to continuous flow processing.

Abstract: A continuous flow procedure for the synthesis of methyl glycosides (Fischer glycosylation) of various monosaccharides using a heterogenous catalyst has been developed. In-depth analysis of the isomeric composition was undertaken and high consistency with corresponding results observed under microwave heating was obtained. Even in cases where addition of water was needed to achieve homogeneity-a prerequisite for the flow experiments-no detrimental effect on the conversion was found.

Biochemical characterization of an ulvan lyase from the marine flavobacterium Formosa agariphila KMM 3901.

Carbohydrates are the product of carbon dioxide fixation by algae in the ocean. Their polysaccharides are depolymerized by marine bacteria, with a vast array of carbohydrate-active enzymes. These enzymes are important tools to establish biotechnological processes based on algal biomass.

Indium- and Zinc-Mediated Acyloxyallylation of Protected and Unprotected Aldotetroses-Revealing a Pronounced Diastereodivergence and a Fundamental Difference in the Performance of the Mediating Metal.

The acyloxyallylation of unprotected aldoses was first demonstrated more than a decade ago as a potentially elegant two-carbon homologation of reducing sugars (upon ozonolysis); however, its application in real case syntheses remained scarce. Following up on such a successful showcase and to answer several pending questions about this attractive transformation, we engaged in an in depth methodological reinvestigation. The epimeric tetroses l-erythrose and d-threose in unprotected and protected form were successfully applied to the indium and also zinc-mediated acyloxyallylation, with the latter being a first for an unprotected sugar.

Large-Scale Synthesis of Crystalline 1,2,3,4,6,7-Hexa--acetyl-l-α-d--heptopyranose.

The higher-carbon sugar l--d--heptose is a major constituent of the inner core region of the lipopolysaccharide (LPS) of many Gram-negative bacteria. All preparative routes used to date require multiple steps, and scalability has been rarely addressed. Here a highly practical synthesis of crystalline 1,2,3,4,6,7-hexa--acetyl-l--α-d--heptopyranose by a simple four-step sequence starting from l-lyxose is disclosed.

Synthesis of [13C4]-labeled 2'-deoxymugineic acid.

The phytosiderophore 2'-deoxymugineic acid (DMA) is exuded via the root system by all grasses (including important crop plants like rice, wheat and barley) to mobilize Fe(III) from soil and improve plant Fe nutrition, crucial for high crop yields. Elucidation of the biogeochemistry of 2'-deoxymugineic acid in the rhizosphere requires its quantification in minute amounts. To this end, (13)C4-DMA was synthesized for the first time, from cheap isotopically labeled starting materials.

Convergent synthesis of 4-O-phosphorylated L-glycero-D-manno-heptosyl lipopolysaccharide core oligosaccharides based on regioselective cleavage of a 6,7-O-tetraisopropyldisiloxane-1,3-diyl protecting group.

The structurally conserved lipopolysaccharide core region of many Gram-negative bacteria is composed of trisaccharides containing 4-O-phosphorylated L-glycero-D-manno-heptose (L,D-Hep) units, which act as ligands for antibodies and lectins. The disaccharides Glc-(1→3)-Hep4P Hep-(1→3)-Hep4P and Hep-(1→7)-Hep4P and the branched trisaccharide Glc-(1→3)-[Hep-(1→7)]-Hep4P, respectively, have been synthesized from a methyl heptopyranoside acceptor in less than 10 steps. The synthetic strategy was based on the early introduction of a phosphotriester at position 4 of heptose followed by a regioselective opening of a 6,7-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl) group allowing for a straightforward access to glycosylation at position 7.

Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.

As an essential constituent of the outer membrane of Gram-negative bacteria, lipopolysaccharide contributes significantly to virulence and antibiotic resistance. The lipopolysaccharide biosynthetic pathway therefore serves as a promising therapeutic target for antivirulence drugs and antibiotic adjuvants. Here we report the structural-functional studies of D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA), an absolutely conserved enzyme in this pathway, from Burkholderia cenocepacia.

Synthesis and antiviral activities of spacer-linked 1-thioglucuronide analogues of glycyrrhizin.

The influenza virus infection remains a significant threat to public health and the increase of antiviral resistance to available drugs generates an urgent need for new antiviral compounds. Starting from the natural, antivirally active compound glycyrrhizin, spacer-bridged derivatives were generated with improved antiviral activity against the influenza A virus infection. Simplified analogues of the triterpene saponin glycyrrhizin containing 1-thio-β-D-glucuronic acid residues have been prepared in good yields by alkylation of 3-amino and 3-thio derivatives of glycyrrhetinic acid with a 2-iodoethyl 1-thio-β-D-glucopyranosiduronate derivative.

Burkholderia cenocepacia lectin A binding to heptoses from the bacterial lipopolysaccharide.

Bacteria from the Burkholderia cepacia complex (Bcc) cause highly contagious pneumonia among cystic fibrosis (CF) patients. Among them, Burkholderia cenocepacia is one of the most dangerous in the Bcc and is the most frequent cause of morbidity and mortality in CF patients. Indeed, it is responsible of "cepacia syndrome", a deadly exacerbation of infection, that is the main cause of poor outcomes in lung transplantation.

Crystal and molecular structure of methyl L-glycero-α-D-manno-heptopyranoside, and synthesis of 1→7 linked L-glycero-D-manno-heptobiose and its methyl α-glycoside.

Methyl l-glycero-α-d-manno-heptopyranoside was synthesized in good yield by a Fischer-type glycosylation of the heptopyranose with methanol in the presence of cation-exchange resin under reflux and microwave conditions, respectively. The compound crystallized from 2-propanol in an orthorhombic lattice of space group P2(1)2(1)2 showing a comparatively porous structure with a 2-dimensional O-H⋯O hydrogen bond network. As model compounds for the side chain domains of the inner core structure of bacterial lipopolysaccharide, l-glycero-α-d-manno-heptopyranosyl-(1→7)-l-glycero-d-manno-heptopyranose and the corresponding disaccharide methyl α-glycoside were prepared.

Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors.

Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11β-HSD2.

Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors.

Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. So far, no selective 11β-HSD2 inhibitor has been developed and neither animal studies nor clinical trials have been reported based on 11β-HSD2 inhibition.