Furanoside Ring Research Articles

Construction of quaternary stereocenters at carbon 2′ of nucleosides

The non-natural nucleosides with a quaternary stereogenic center at C2′ are crucial to drug discovery. They have become a cornerstone for the treatment of cancer and various viral infections as exemplified by gemcitabine and sofosbuvir. Major research effort has been expended to gain synthetic access to these nucleoside analogues with a significant steric bulk at C2′ in the furanoside ring. The 2′-ketonucleosides and 2′-deoxy-2′-methylenenucleosides emerged as key intermediates in these synthetic strategies. For example, α-face addition of methyl lithium to the 2′-ketonucleosides followed by fluorination of resulting tertiary arabino alcohol with DAST provided 2′-fluoro-2′-C-methyluridine - a core nucleoside component of sofosbuvir. The α-face addition of HCN or HN3 to the 2′-deoxy-2′-methylene nucleosides gave access to the synthetically versatile 2′-cyano-2′-C-methyl and 2′-azido-2′-C-methyl nucleosides. Likewise, the addition of diazomethane to the 2′-exomethylene group gave access to the 2′-spirocyclopropyl analogue. This review primarily discusses synthetic strategies which employs natural nucleosides as substrates but selected approaches involving coupling of the preelaborated sugar precursors with nucleobases are also examined.

Influence of per-O-sulfation upon the conformational behaviour of common furanosides.

The studies on the recently discovered pyranoside-into-furanoside rearrangement have led us to conformational investigations of furanosides upon their total sulfation. Experimental NMR data showed that in some cases drastic changes of the ring conformation occurred while sometimes only the conformation of the exocyclic C4–C5 linkage changed. Herein we describe a combined quantum chemical and NMR conformational investigation of three common monosaccharide furanosides as their propyl glycosides: α-mannose, β-glucose and β-galactose. Full exploration of the furanoside ring by means of ab initio calculations was performed and coupling constants were calculated for each of the low-energy conformers. The results demonstrated preferred trans-orientation of H4–H5 protons in the non-sulfated molecules which changed to gauche-orientation upon sulfation. The effect is less pronounced in the galactosides. For all the studied structures changes in the conformational distribution were revealed by quantum mechanical calculations, that explained the observed changes in intraring coupling constants occurring upon introduction of sulfates.

Pyranoside-into-furanoside rearrangement: new reaction in carbohydrate chemistry and its application in oligosaccharide synthesis.

Great interest in natural furanoside-containing compounds has challenged the development of preparative methods for their synthesis. Herein a novel reaction in carbohydrate chemistry, namely a pyranoside-into-furanoside (PIF) rearrangement permitting the transformation of selectively O-substituted pyranosides into the corresponding furanosides is reported. The discovered process includes acid-promoted sulfation accompanied by rearrangement of the pyranoside ring into a furanoside ring followed by solvolytic O-desulfation. This process, which has no analogy in organic chemistry, was shown to be a very useful tool for the synthesis of furanoside-containing complex oligosaccharides, which was demonstrated by synthesizing disaccharide derivatives α-D-Galp-(1→3)-β-D-Galf-OPr, 3-O-s-lactyl-β-D-Galf-(1→3)-β-D-Glcp-OPr, and α-L-Fucf-(1→4)-β-D-GlcpA-OPr related to polysaccharides from the bacteria Klebsiella pneumoniae and Enterococcus faecalis and the brown seaweed Chordaria flagelliformis.

Recent Developments Towards the Synthesis of Varitriol: An Antitumour Agent from Marine Derived Fungus Emericella Variecolor

Marine natural products are recognized as a fruitful source of drug development due to their rare structural entities and diverse biological activities, and consequently, publicized number of metabolites as new medicines. Although extensive progress has been made in identifying novel bioactive molecules from marine source, endeavors to explore these molecules for medicinal applications are much needed. Marine fungi are one of the important sources of natural products, exhibiting a wide range of biological activities. (+)-Varitriol, isolated from the marine fungus Emericella variecolor, has shown 100-fold increased potency over the mean toxicity towards variety of cancer cell lines. Hence (+)-varitriol, an antitumour marine natural product has been a fascinating target for total synthesis over the last decade. The intense search for developing new approaches coupled with its biological activity has resulted in a wealth of methods towards the syntheses of this molecule. But, unfortunately only limited analogues have been synthesized and evaluated for their biological activities. Thus, there are still demands to modify aromatic part as well as sugar moiety of varitriol, which could provide the opportunity for further SAR studies to discover potential lead anticancer agents. This review describes the different strategies developed for the syntheses of varitriol and its analogues in various laboratories around the world covering literature from 2002 till date. The construction of the challenging and fashionable furanoside ring as well as substituted styrene derivatives are crucial steps in most of the reported synthetic endeavors. Keywords: Antitumour agent, asymmetric synthesis, carbohydrate, marine fungi, natural product, varitriol.

Synthesis of chiral macrocyclic sugar-peptide hybrids by ring closing metathesis approach

Furanoside and peptide appended bis-olefins afforded monomeric 12- to 18-membered cyclic olefins fused to furanoside rings via RCM approach using Grubbs’ Catalyst.

1,2,3,3′,4′,6′-Hexaacetyl-4,6-O-benzylidenesucrose

In the title compound, C31H38O17, the 1,3-dioxane and pyran­oside rings both show 4 C 1 chair conformations while for the d-fructofuran­oside moiety an envelop 3E conformation is observed. The phenyl ring is oriented almost perpendicular to the 1,3-dioxane ring [dihedral angle = 79.3 (2)°], and the acetate groups are equatorial for the pyran­oside ring and axial for the furan­oside ring. The analysis of potential hydrogen bonds shows both intra- and inter­molecular C—H⋯O contacts to be present.

Free radical 5-exo-dig cyclization as the key step in the synthesis of bis-butyrolactone natural products: experimental and theoretical studies

Radical cyclization reactions were performed by 5-exo-dig mode to yield cis-fused bicyclic systems, leading to the synthesis of bis-butyrolactone class of natural products. The study was aimed at understanding the impact of alkyl side chains of furanoside ring systems in L-ara configuration on the radical cyclization. It was amply demonstrated by experimental studies that the increase in the length of the alkyl side chain has an effect on the cyclization: while efficient cyclization reactions could be realized with methyl and ethyl side chains, the yields were significantly reduced in the case of n-pentyl side chain. Theoretical studies using DFT and (RO)MP2 methods were carried out to analyze the influence of the substitution pattern on the cyclization barriers.

Approach for the Simulation and Modeling of Flexible Rings: Application to the α-D-Arabinofuranoside Ring, a Key Constituent of Polysaccharides from Mycobacterium tuberculosis.

A number of lower organisms (bacteria, fungi, and parasites) produce glycoconjugates that contain furanose rings. Of particular interest to our group are cell wall polysaccharides from mycobacteria, including the human pathogen, Mycobacterium tuberculosis, which contain a large number of arabinofuranose resides. As part of a larger project on the conformational analysis of these molecules, we report here molecular dynamics simulations on methyl α-D-arabinofuranoside (1) using the AMBER force field and the GLYCAM carbohydrate parameter set. We initially studied the ability of this method to predict rotamer populations about the hydroxymethyl group (C4-C5) bond. Importantly, we show that simulation times of up to 200 ns are required in order to obtain convergence of the rotamer populations for this ring system. We also propose a new charge derivation approach that accounts for the flexibility of the furanoside ring by taking an average of the charges from a large number of conformers across the psuedorotational itinerary. The approach yields rotamer populations that are in good agreement with available NMR data and, in addition, provides insight into the nature of the puckering angle and amplitude in 1.

Cu(I)‐Catalyzed Cycloaddition of Constrained Azido‐Alkynes: Access to 12‐ to 17‐Membered Monomeric Triazolophanes Incorporating Furanoside Rings.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cu(I)-Catalyzed cycloaddition of constrained azido-alkynes: access to 12- to 17-membered monomeric triazolophanes incorporating furanoside rings

A strained monomeric 12-membered triazolophane was formed by the Cu(I)-catalyzed intramolecular cycloaddition of an azide to an alkyne having a constrained tether incorporating an aromatic ring and a furanoside ring. Similar cycloadditions of azido-alkynes having ester, furanoside and peptidic tethers led to the formation of monomeric triazolophanes of higher ring sizes.

Synthesis and Conformational Analysis of Arabinofuranosides, Galactofuranosides and Fructofuranosides

AbstractFor Abstract see ChemInform Abstract in Full Text.

Crystal Structure and Solid‐State 13C NMR of Methyl α‐d‐Mannofuranoside †

The crystal structure of methyl α‐d‐mannofuranoside was determined by X‐ray crystallography. The C‐1–C‐2, C‐2–C‐3, C‐3–C‐4, C‐4–O and O‐4–C‐1 distances within the furanoside ring are 1.513(2), 1.523(2), 1.516(2), 1.445(2) and 1.422(2) Å, respectively. The hydrogen bonding consists of O–H–O interactions which include the anomeric oxygen but exclude the ring oxygen atom. The two hydroxyls OH‐6 and OH‐2 are H‐bond acceptors and donors with H···O distances of 1.92–1.93 Å, whereas the OH‐3 and OH‐5 are only H‐bond donor [H···O distance of 2.04(2) Å]. Additionally, OH‐6 participates in a weak hydrogen bond to the anomeric oxygen [H···O distance of 2.19(3) Å]. The crystalline methyl α‐d‐mannofuranoside adopts an 3 E ring conformation. The analysis of 13C CPMAS NMR chemical shifts for solid methyl α‐d‐mannofuranoside confirm such H‐bonding pattern. †This paper is dedicated to Professor Gérard Descotes on the occasion of his 70th birthday.

An expedient approach to internally functionalized chiral dendrimers: synthesis of a dendritic molecule incorporating furanoside skeleton.

In an approach to chiral dendritic molecules, a dendrimer incorporating pentose units in the interior and hexose units in the periphery is built up on a 1, 3, 5-trisubstituted aromatic core by using 1,2:5,6-diisopropylidene glucose as the carbohydrate precursor and a 3, 5-disubstituted aromatic unit as the branching block. The carbohydrate moiety also provides internal functionalities in the form of hemiacetal moiety of the furanoside ring.

Synthesis of chiral oxepinopyran and oxepinooxepane systems from 1,2-isopropylidene furanoside ring-fused cyclic ether derivatives through 4- O-allyl nitrone and nitrile oxide cycloadditions

A novel strategy was developed by which chiral oxepinopyran and oxepinooxepane derivatives were synthesised from 1,2-isopropylidene furanoside fused pyran and oxepane derivatives by the cycloaddition of 4- O-allyl nitrone or nitrile oxide species generated from the furanoside ring

Synthesis of chiral pyranocyclohexane, oxepanocyclohexane, and furylpyran and -oxepane systems by the application of intramolecular nitrone and nitrile oxide cycloaddition of carbohydrate derivatives

Chiral nonracemic pyranocyclohexanes 7 and 8 and oxepanocyclohexane 11 and 12 were obtained from a single 1,2-isopropylidene-3- O-cyclohexenyl carbohydrate aldehyde 4 via intramolecular nitrile oxide cycloaddition, and were converted to 2-(2′-tetrahydrofuryl)pyran 28, which incorporates the lasalocid skeleton, and the related oxepane derivative 32 respectively, through modification of the furanoside ring by applying 2- O-allyl carbohydrate nitrone cycloaddition.

Chelation-controlled regioselective endo cleavage and stereoselective C-1 alkylation of pentofuranosides

Combinations of Lewis acids and nucleophilic reagents trigger endo-opening of the furanoside ring of methyl furanosides 1, 10 and 13, resulting in the attachment of the nucleophilic group at C-1 of the carbohydrate. The stereoselectivity in the C–C bond-forming step is low for the 2-deoxyfuranosides but very high (dr 1∶99) for the furanosides carrying a methoxy group in the 2-position when a combination of TiCl4 and Me2Zn is used. Different selectivities are obtained with Me2Zn as compared with Me3Al. Reagents based on several organometallic reagents of Al, Si, Ti and Zn in combination with TiCl4 can be used.

ChemInform Abstract: Regioselective Introduction of 2‐Propynyl Groups into the C‐2 or C‐3 Position of Furanoside Ring.

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Regioselective Introduction of 2-Propynyl Groups into the C-2 or C-3 Position of Furanoside Ring

Abstract The reaction of methyl 2,3-anhydro-α-d-ribofuranoside or methyl 2,3-anhydro-5,6-O-cyclohexylidene-α-d-allofuranoside with 2-propynyl metallic reagents exclusively gave the corresponding 2-C-(2-propynyl)-arabino-pentofuranosides and 2-C-(2-propynyl)-altro-hexofuranosides, respectively. In contrast, the β-anomers were selectively attacked at the position 3 to afford the corresponding 3-C-(2-propynyl)furanosides.

ChemInform Abstract: Regioselective Introduction of Allylic Groups into the C‐2 or C‐3 Position of Furanoside Rings.

AbstractThe α‐furanoside (I) reacts with the allylic Grignard compounds (II) to form predominantly the 2‐deoxy‐2‐C‐alkenylfuranosides (III).

Regioselective Introduction of Allylic Groups into the C-2 or C-3 Position of Furanoside Rings

Abstract The reaction of α-anomers of methyl 2,3-anhydro-D-ribo- and D-allo-furanosides with allylic Grignard reagents predominantly gave the corresponding 2-deoxy-2-C-alkenylfuranosides. In contrast, their β-anomers selectively gave 3-C-alkenyl derivatives. Preparation of a synthon of the C-4∼C-9 fragment common to various 16-member macrolide antibiotics is also described.