ABSTRACT
This review focuses on the chemical structure, biosynthesis and synthesis of free and glycosylated pyridinolines (Pyds), fluorescent collagen cross-links, with a pyridinium salt structure. Pyds derive from the degradation of bone collagen and have attracted attention for their use as biochemical markers of bone resorption and to assess fracture risk prediction in persons suffering from osteoporosis, bone cancer and other bone or collagen diseases. We consider and critically discuss all reported syntheses of free and glycosylated Pyds evidencing an unrevised chemistry, original and of general utility, analysis of which allows us to also support a previously suggested non-enzymatic formation of Pyds in collagen better rationalizing and justifying the chemical events.
Subject(s)
Amino Acids/chemistry , Collagen/chemistry , Amino Acids/chemical synthesis , Amino Acids/metabolism , Animals , Bone and Bones/chemistry , Bone and Bones/metabolism , Chemistry Techniques, Synthetic/methods , Collagen/chemical synthesis , Collagen/metabolism , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , Glycosylation , Humans , Synovial Membrane/chemistry , Synovial Membrane/metabolismABSTRACT
A simple protocol for the synthesis of N-perfluoroacylated and N-acylated glycals of neuraminic acid, with a secondary cyclic amine (morpholine or piperidine) at the 4α position, has been set-up, starting from peracetylated N-acetylneuraminic acid methyl ester that undergoes, sequentially to its direct N-transacylation followed by a C-4 amination, a ß-elimination, and a selective hydrolysis of the ester functions, without affecting the sensitive perfluorinated amide.
Subject(s)
Amines/chemistry , Carbohydrates/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Ether/chemistry , Fluorine Compounds/chemical synthesis , Neuraminic Acids/chemistry , Neuraminidase/antagonists & inhibitors , Acylation , Carbohydrates/pharmacology , Cyclization , Enzyme Inhibitors/pharmacology , Fluorine Compounds/pharmacology , Molecular Structure , Structure-Activity Relationship , Vibrio cholerae/drug effects , Vibrio cholerae/enzymologyABSTRACT
The chemoselective synthesis of the 1,7-lactones of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-d-glycero-d-galacto-nononic acid is accomplished in two steps: a simple treatment of the corresponding free sialic acid with benzyloxycarbonyl chloride and a successive hydrogenolysis of the formed 2-benzyloxycarbonyl 1,7-lactone. The instability of the 1,7-lactones to protic solvents has been also evidenced together with the rationalization of the mechanism of their formation under acylation conditions. The results permit to dispose of authentic 1,7-sialolactones to be used as reference standards and of a procedure useful for the preparation of their isotopologues to be used as inner standards in improved analytical procedures for the gas liquid chromatography-mass spectrometry (GLC-MS) analysis of 1,7-sialolactones in biological media.
Subject(s)
Lactones/chemical synthesis , Sialic Acids/chemical synthesis , Carbohydrate Conformation , Lactones/chemistry , Sialic Acids/chemistry , StereoisomerismABSTRACT
An efficient short protocol for the preparation of N-perfluoroacylated glycals of neuraminic acid, by simple short treatment of differently protected N-acetylneuraminic acid with perfluorinated anhydrides in acetonitrile at 135 degrees C, is reported, together with a rationalitazion of the reaction that allows the alternative formation of N-perfluoroacylated 1,7-lactones to be previewed under the same reaction conditions.
Subject(s)
Anhydrides/chemistry , Antiviral Agents/chemistry , Fluorine Compounds/chemistry , N-Acetylneuraminic Acid/chemistry , Polysaccharides/chemistry , Molecular Structure , N-Acetylneuraminic Acid/analogs & derivativesSubject(s)
Amides/chemistry , Anhydrides/chemistry , Fluorine/chemistry , Acylation , Molecular StructureABSTRACT
N-Acetylneuraminic acid is transformed into its until now unavailable and rather unwieldy 1,7-lactone, via the manageable 2-benzyloxycarbonyl N-acetylneuraminic acid 1,7-lactone which generates the free lactone in quantitative yield by hydrogenolysis.
Subject(s)
Lactones/chemical synthesis , Sialic Acids/chemical synthesis , Carbohydrate Conformation , Lactones/chemistry , Sialic Acids/chemistry , StereoisomerismABSTRACT
The present report describes a method for the quantification of N-acetyl- and N-glycolylneuraminic acids without any derivatization, using their (13)C(3)-isotopologues as internal standards and a C(18) reversed-phase column modified by decylboronic acid which allows for the first time a complete chromatographic separation between the two analytes. The method is based on high-performance liquid chromatographic coupled with electrospray ion-trap mass spectrometry. The limit of quantification of the method is 0.1mg/L (2.0ng on column) for both analytes. The calibration curves are linear for both sialic acids over the range of 0.1-80mg/L (2.0-1600ng on column) with a correlation coefficient greater than 0.997. The proposed method was applied to the quantitative determination of sialic acids released from fetuin as a model of glycoproteins.
Subject(s)
Chromatography, High Pressure Liquid/methods , Neuraminic Acids/analysis , Sialic Acids/analysis , alpha-Fetoproteins/chemistry , Animals , Boronic Acids/chemistry , Calibration , Cattle , Hydrolysis , Isotopes/chemistry , Reference Standards , Sensitivity and Specificity , Tandem Mass Spectrometry/methods , alpha-Fetoproteins/metabolismABSTRACT
This paper demonstrates that the crystallization of 3beta-acetoxy-14alpha,15alpha-epoxy-5alpha-cholest-8-en-7-one from methanol affords the 3beta-acetoxy-9alpha-methoxy-15alpha-hydroxycholest-8(14)-en-7-one. The structure of this steroid, which shows an apparently anomalous UV absorption maximum, is determined by high field NMR experiments, supporting the coupling constant values assignments and the NOE contacts by a conformational study through theoretical calculations at the B3LYP/6-31G* level. The computational study also justifies the observed UV absorption of the steroid, thus demonstrating the usefulness of computer chemistry in providing support for the identification of unknown compounds.
Subject(s)
Cholestenones/chemistry , Epoxy Compounds/chemistry , Methanol/chemistry , Models, Chemical , Sterols/chemistry , Carbon Isotopes , Magnetic Resonance Spectroscopy , Molecular Conformation , Protons , Rotation , Spectrophotometry, Ultraviolet , ThermodynamicsABSTRACT
The paper reports some successful results on the first fully stereoselective total synthesis of the collagen cross-link pyridinolines. All stereogenic centers are stereoselectively introduced using Williams glycine template methodology, and oxazinones are used as a source of chirality and as easily removable protecting groups of the amino acidic functionalities during the assembly of the pyridinoline nucleus.
Subject(s)
Amino Acids/chemical synthesis , Biomarkers/chemistry , Chemistry, Organic/methods , Collagen/metabolism , Amino Acids/metabolism , Biomarkers/metabolism , Humans , Hydroxylysine/chemistry , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
The first total synthesis of alpha-D-glucopyranosyl-(1-->2)-beta-D-galactopyranosyl-O-pyridinoline using a short "one-pot" assembly of its 1,4,5-trisubstituted 3-hydroxypyridinium ring is reported.
Subject(s)
Disaccharides/chemical synthesis , Joint Diseases/metabolism , Pyridines/chemical synthesis , Disaccharides/metabolism , Humans , Magnetic Resonance Spectroscopy , Pyridines/metabolism , Spectrometry, Mass, Electrospray IonizationABSTRACT
This paper reports the first chemical synthesis of alpha-D-glucopyranosyl-(1-->2)-beta-D-galactopyranosyl-O-hydroxylysine, a glycoside of hydroxylysine important as indicator of skin and bone collagen turnover, starting with commercial compounds.
