Acyclic Carbohydrate Research Articles

GLYCOLIPOTRIPEPTIDE (N-LACTITOL-Gly)2-LysС16 AND ITS FLUORESCENTLY LABELED ANALOGUE FOR VISUALIZATION OF VECTOR SYSTEMS FOR BIOLOGICALLY ACTIVE SUBSTANCES DELIVERY TO TARGET CELLS

The work is devoted to the preparation of a carbohydrate derivative of lipotripeptide (N-lactitol-Gly)2-LysC16 of irregular structure with two terminal residues of D-galactose, a branching link based on aliphatic L-lysine and its carbohydrate-free analog with 1-pyrenbutanol as a fluorescent label in a hydrophobic fragment. The developed synthesis scheme includes universal approaches of peptide chemistry, as well as the stages of formation of an acyclic carbohydrate based on lactose in the hydrophilic domain of amphiphile. The compounds are designed to create compositions of vector BAS delivery systems with the ability to visualize the process of interaction with target cells.

Multicentered hydrogen bonding in 1-[(1-de-oxy-β-d-fructo-pyranos-1-yl)aza-nium-yl]cyclo-pentane-carboxyl-ate ('d-fructose-cyclo-leucine').

The title compound, C12H21NO7, (I), is conformationally unstable; the predominant form present in its solution is the β-pyran-ose form (74.3%), followed by the β- and α-furan-oses (12.1 and 10.2%, respectively), α-pyran-ose (3.4%), and traces of the acyclic carbohydrate tautomer. In the crystalline state, the carbohydrate part of (I) adopts the 2 C 5 β-pyran-ose conformation, and the amino acid portion exists as a zwitterion, with the side chain cyclo-pentane ring assuming the E 9 envelope conformation. All heteroatoms are involved in hydrogen bonding that forms a system of anti-parallel infinite chains of fused R 3 3(6) and R 3 3(8) rings. The mol-ecule features extensive intra-molecular hydrogen bonding, which is uniquely multicentered and involves the carboxyl-ate, ammonium and carbohydrate hy-droxy groups. In contrast, the contribution of inter-molecular O⋯H/H⋯O contacts to the Hirshfeld surface is relatively low (38.4%), as compared to structures of other d-fructose-amino acids. The 1H NMR data suggest a slow rotation around the C1-C2 bond in (I), indicating that the intra-molecular heteroatom contacts survive in aqueous solution of the mol-ecule as well.

From Mannose to Small Amphiphilic Polyol: Perfect Linearity Leads To Spontaneous Aggregation

Terminally unsaturated and diastereochemically pure polyol derived from d-mannose shows spontaneous aggregation behavior in water solution. In order to study and clarify this unforeseen phenomenon, a conformational study based on NMR spectroscopy combined with ab initio structure analysis using the COSMO-solvation model was pursued. The results, together with X-ray diffraction studies, suggest a low energy linear conformation for this particular substrate both in solid states and in solution. For such small-sized acyclic carbohydrate derivatives, the linear conformation appears to be a key prerequisite for the unusual molecular self-assembly reported herein.

Improved binding affinity and interesting selectivities of aminopyrimidine-bearing carbohydrate receptors in comparison with their aminopyridine analogues

Due to the problems with the exact prediction of the binding properties of an artificial carbohydrate receptor, the identification of characteristic structural features, having the ability to influence the binding properties in a predictable way, is of high importance. The purpose of our investigation was to examine whether the previously observed higher affinity of 2-aminopyrimidine-bearing carbohydrate receptors in comparison with aminopyridine substituted analogues represents a general tendency of aminopyrimidine-bearing compounds. Systematic binding studies on new compounds consisting of 2-aminopyrimidine groups confirmed such a tendency and allowed the identification of interesting structure-activity relationships. Receptors having different symmetries showed systematic preferences for specific glycosides, which are remarkable for such simple receptor systems. Particularly suitable receptor architectures for the recognition of selected glycosides were identified and represent a valuable base for further developments in this field.

2,3,4,6-tetra-O-Acetyl-D-Gluconic Acid: Crystal Structure and Application in the Synthesis of N-(D-gluconyl) Derivatives of D-Glucosamine

2,3,4,6-tetra-O-Acetyl-D-gluconic acid was synthesized and coupled with 1,3,4, 6-tetra-O-acetyl-2-amino-2-deoxy-β-D-glucopyranose and diosgenyl 3,4,6-tri-O-acetyl-2-amino-2-deoxy-β-D-glucopyranoside to afford N-gluconyl derivatives of diosgenyl 2-amino-2-deoxy-D-glucopyranoside using the methods of solution-phase peptide synthesis. Both coupling reactions suffered from acetyl O→N migration, which caused the N-acetyl derivatives to be formed together with the N-(D-gluconyl) derivatives of D-glucosamine. Additionally, single-crystal X-ray diffraction and high-resolution NMR spectral data for 2,3,4,6-tetra-O-acetyl-D-gluconic acid were analyzed to reveal that this acyclic carbohydrate has adopted the 2G− conformation instead of a typical zigzag conformation. The planarity and cis geometry of the acetoxyl groups are demonstrated.

A Unique Synthetic Method to Convert a D‐Sugar into 2‐Deoxy‐L‐ribitol Through Carbonyl Translocation

AbstractA unique and highly efficient radical process was developed to prepare 2‐deoxy‐L‐ribitol. The radical cyclization precursor was prepared over several steps from D‐sugars. Radical cyclization followed by fragmentation gave exclusively the desired product, with carbonyl translocation in an acyclic carbohydrate system. The radical process was optimized to avoid the formation of byproducts. The reaction mechanism was studied by the concentration effect, which indicated that both the radical cyclization and the fragmentation steps are relatively rapid. The stereochemistry of the 2‐deoxy‐L‐ribitol was confirmed by X‐ray crystal structure. By using this synthetic approach, a D‐sugar derivative could be transformed into 2‐deoxy‐L‐ribose in a single radical reaction.

ChemInform Abstract: 6-Exo Free Radical Cyclization of Acyclic Carbohydrate Intermediates: A New Synthetic Route to Enantiomerically Pure Polyhydroxylated Cyclohexane Derivatives.

The 6-exo free radical cyclization of conveniently functionalized acyclic carbohydrate derivatives is a new and efficient method for the asymmetric synthesis of polyhydroxylated cyclohexane compounds (aminocyclitols, pseudosugars). The scope and versatility of this synthetic route has been analyzed by changing the absolute configuration of the radical precursors and the nature of the radical trap. The yield and stereoselectivity in this process is very structure dependent

ChemInform Abstract: Carbocycles from Carbohydrates: A Free Radical Route to Aminocyclitol Derivatives.

Abstract Some derivatives of (1R,2R,3R,4S,5R) and 1R,2R,3R,4R,5S)-5-amino-1,2,3,4-cyclohexanetetrol have been synthesized from acyclic carbohydrate intermediates via 6-exo free radical cyclization.

Highly Effective Acyclic Carbohydrate Receptors Consisting of Aminopyridine, Imidazole, and Indole Recognition Units

Neutral imidazole/aminopyridine- and indole/aminopyridine-based receptors, 1 and 2, have been established as highly effective and selective carbohydrate receptors. These receptors effectively recognise neutral carbohydrates through multiple interactions, including neutral hydrogen bonds and CH...pi interactions between the sugar CH groups and the aromatic rings of the receptors. The design of these receptors was inspired by the binding motifs observed in the crystal structures of protein-carbohydrate complexes. The formation of very strong complexes with beta-glucopyranoside 5, beta-maltoside 8, and alpha-maltoside 9 in organic media has been characterised by 1H NMR spectroscopy and confirmed by a second, independent technique, namely fluorescence spectroscopy. The syntheses, molecular-modelling studies, binding properties of the receptors 1 and 2 toward selected mono- and disaccharides as well as comparative binding studies with receptors 3 and 4 are described.

Acyclic tautomers in crystalline carbohydrates: the keto forms of 1-deoxy-1-carboxymethylamino-D-2-pentuloses (pentulose-glycines).

NMR and X-ray diffraction studies on acyclic carbohydrate keto tautomers of N-(1-deoxy-d-erythro-2-pentulos-1-yl)- and N-(1-deoxy-d-threo-2-pentulos-1-yl)glycines (ribulose-glycine, 1 and xylulose-glycine, 2), are reported. In aqueous solutions, both 1 and 2 exist as a tautomeric mixture, with the beta-furanose as a major form, followed by the alpha-furanose and the acyclic keto tautomer. Both 1 and 2 crystallize as zwitterions in the acyclic keto form. Solid-state 13C NMR spectra reveal the existence of two crystallographically independent molecules in 2 but only one in crystalline 1. The structure of 2 was solved by X-ray diffraction; in the crystal, two conformational isomers, 2a and 2b in a 1:1 ratio, were identified. The conformers are packed in stacks of similar molecules, with a system of intermolecular hydrogen bonds involving all hydroxyl, ammonium, and carboxyl groups. The structural data indicate that the sugar portion of acyclic 2 adopts conformations similar to those proposed for the parent d-xylulose.

Synthesis of chiral, densely functionalized medium-sized rings from carbohydrate precursors via regioselective exo/ endo-primary alkyl radical cyclizations

The first 8- endo-trig and 7- exo-dig carbocyclizations of primary alkyl free radicals on acyclic carbohydrate templates derived from d-glucose, leading to chiral and polyfunctionalized medium-sized carbocycles are described.

Synthetic studies towards the total synthesis of olivin: Synthesis of a fully functionalized alkyne appropriate for the benzannulation reaction

A synthetic strategy for the synthesis of olivin has been developed which features a benzannulation reaction of a Fischer carbene complex in the assembly of the tricyclic core of the molecule containing the acyclic carbohydrate side chain and the phenol functions differentiated. In this work, a synthesis of a key alkyne is developed to be used in a benzannulation reaction that constructs the B-ring of olivin. This alkyne incorporates four of the five asymmetric centers in the aglycone of olivin. The synthesis of this alkyne begins with the exclusively syn selective Mukaiyama aldol reaction of 2-trimethylsiloxyfuran with the 2S,3R-dihydroxybutanal protected as its acetonide. Conjugate addition of a vinyl cuprate to the butenolide obtained from this reaction gives a single stereoisomer of an intermediate that has all of the chiral centers of the acyclic carbohydrate side chain. The final carbon in the alkyne is introduced by a Corey-Fuchs reaction which is used to install the alkyne function. The synthesis of the alkyne is accomplished in 15 steps (6 % overall yield) and can provide gram quantities of material. Initial evaluation of the key benzannulation step was performed with alkyne 45 and carbene complex 44 which demonstrates the viability of a synthetic strategy that employs the reaction of an aryl Fischer carbene complex with a complex alkyne containing the functionality needed for the synthesis of olivin.

Synthesis of 4,6-diamino-5-(polyhydroxyalkylamido)pyrimidines: conformation of the sugar chain

Condensation of 4,5,6-triaminopyrimidine with ethyl glycolate, d-ribono-1,4-lactone, d-allono-1,4-lactone, d-glucono-1,5-lactone, and l-gulono-1,4-lactone led to the corresponding 4,6-diamino-5-(hydroxyalkylamido)pyrimidines ( 1a– e). The conformations in acidic aqueous solution of these acyclic carbohydrate derivatives were determined from the proton–proton NMR coupling constants at 300 MHz. The polyhydroxyalkyl chain of compounds 1b– e adopt sickle conformations in order to avoid the 1,3-parallel interactions between hydroxyl groups present in the planar zigzag conformer. Cyclization of 4,6-diamino-5-(hydroxyacetamido)pyrimidine ( 1a) afforded 8-(hydroxymethyl)adenine ( 2a), which was acetylated to give 2f. The 13C NMR spectra of compounds 1a– e and 2a and f are also reported.

A cytosine analogue containing a conformationally flexible acyclic linker for triplex formation at sites with contiguous G-C base pairs

Two nucleoside derivatives of the pyrimidine bases T and m 5oxC have been prepared with flexible acyclic carbohydrate linkers. A new procedure, beginning with ( R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol permits the preparation of the stereochemically pure acyclic derivatives of both protected nucleoside analogues without contamination by a problematic rearrangement product. By simply increasing the flexibility of the carbohydrate portion of the am 5oxC nucleoside derivative, 15-mer triplexes containing five contiguous G-C base pairs exhibit a 7–8°C increase in T m value.

The effect of substituent position on the liquid crystalline properties of dodecyl-D-xylitols

Recently we have been concerned with a systematic and fundamental investigation into the effects of the linking group on the lyotropic and thermotropic properties of aliphatic substituted acyclic carbohydrate systems. For this purpose, we chose to study the selfassembling behaviour of alkyl substituted xylitols where the aliphatic chain was attached to the xylitol moiety via ether, ester and thioether linkages. We have extended this work and, in this current study, we report the effects on the self-assembling properties of sequentially moving the position of a dodecyl chain in acyclic x-O-dodecyl-D-xylitols. This work was used for a direct comparison with results reported on cyclic systems such as the dodecyl x-O-beta-Dglucopyranosides.

1,3-Parallel C/ /O interactions in acyclic carbohydrates: The crystal and molecular structure of 1-deoxy-1-nitro- d-altritol

The crystal structure of 1-deoxy-1-nitro- d-altritol ( 1; C 7H 13NO 7; space group P2 1) was resolved to a final conventional residual factor of R 0.081. The molecules showed a sickle conformation in which a 1,3-parallel interaction (C/ /O) between C-6 and O-3 is tolerated, thus avoiding a 1,3-parallel interaction (O/ /O) between O-3 and O-5 in a planar zigzag conformation. Interestingly, the bent conformation, which avoids all such interactions, was not adopted. The observed conformation resembles that of d-altritol and d-altritol hexaacetate. A systematic search for the occurrence of such C/ /O interactions in the solid state conformations of acyclic carbohydrate derivatives revealed that this is the conformation which usually is observed in those cases where compounds or part of compounds are of ribo configuration, but with a few remarkable exceptions such as ribitol itself.

Mixed oligonucleotide analogues with an acyclic carbohydrate moiety and a N-cyanoguanidine functionality

Mixed aligonucleotide analogues having a backbone structure with a N-cyanoguanidine functionality and an acyclic sugar moiety were synthesized. This combination, however, has a detrimental effect on duplex stability of DNA-DNA hybrids.

6-Exo free radical cyclization of acyclic carbohydrate intermediates: a new synthetic route to enantiomerically pure polyhydroxylated cyclohexane derivatives

The 6-exo free radical cyclization of conveniently functionalized acyclic carbohydrate derivatives is a new and efficient method for the asymmetric synthesis of polyhydroxylated cyclohexane compounds (aminocyclitols, pseudosugars). The scope and versatility of this synthetic route has been analyzed by changing the absolute configuration of the radical precursors and the nature of the radical trap. The yield and stereoselectivity in this process is very structure dependent

Carbocycles from carbohydrates: a free radical route to aminocyclitol derivatives

Some derivatives of (1 R,2 R,3 R,4 S,5 R) and 1 R,2 R,3 R,4 R,5 S)-5-amino-1,2,3,4-cyclohexanetetrol have been synthesized from acyclic carbohydrate intermediates via 6-exo free radical cyclization.

Synthesis of acyclic analogues of sesbanimides A and B

The synthesis of sesbanimide analogues 3a and 3b is described. In these analogues the glutarimide and the hemiketal ring are separated by an acyclic carbohydrate moiety containing three carbon atoms with the same absolute configuration at the stereogenic centers, as in natural (+)-sesbanimide A.