ABSTRACT
Polymer-supported butyltin(IV) reagents have been surveyed for regioselectivity in acetylation of sucrose. Polymer-supported butyltin(IV) dichloride 8 catalysed the acetylation of sucrose to give a 59% yield of 6-O-acetyl sucrose 3, the precursor of sucralose. The yield is close to that of a previously reported process involving dibutyltin(IV) oxide (Bu2SnO). The spent polymeric resin could readily be regenerated and can be subsequently used in further synthetic reactions.
Subject(s)
Sucrose/metabolism , Tin Compounds/chemical synthesis , Acetylation , Carbohydrate Conformation , Carbohydrate Sequence , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Molecular Structure , Sucrose/analogs & derivatives , Tin Compounds/toxicityABSTRACT
As part of our ongoing study to survey potent LPS antagonists, the following six compounds were synthesized in an efficient manner: 3-carboxypropyl and carboxymethyl 2-deoxy-2-(2,2-difluorotetradecanamido)-4-O-phosphono-3-O-[(R)-3- (tetradecanoyloxy)tetradecanoyl]-alpha- and beta-D-glucopyranosides (11 and 23; 32 and 36), as well as the non-fluorinated equivalents, carboxymethyl 2-deoxy-4-O-phosphono-2-tetradecanamido-3-O-[(R)-3-(tetradecano yloxy)- tetradecanoyl]-alpha-D-glucopyranoside (44) and carboxymethyl 2-deoxy-2-[(R)-3-(hydroxy)tetradecanamido]-4-O-phosphono-3-O-[(R)- 3- (tetradecanoyloxy)tetradecanoyl]-alpha-D-glucopyranoside (48). Of these compounds, 32 was most pronounced in terms of LPS-antagonistic activity.
Subject(s)
Glucosides/chemical synthesis , Carbohydrate Conformation , Carbohydrate Sequence , Cells, Cultured , Escherichia coli/chemistry , Glucosides/pharmacology , Glycolipids/pharmacology , Lipid A/analogs & derivatives , Lipid A/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Molecular Structure , Prednisolone/pharmacology , Salmonella/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
N-(9-Fluorenylmethoxycarbonyl)-O-([O-(2-acetamido-3,4,6-tri-O-acet yl-2- deoxy-alpha-D-galactopyranosyl)-(1-->3)-O-[(2,3,4-tri-O-benzyl-alpha-L- fucopyranosyl)-(1-->2)]-O-(4,6-di-O-acetyl-beta-D-galactopyranosyl)- (1-->3)-O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)- (1-->6)]-O-[(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D- galactopyranosyl)-(1-->3)-O-[(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)- (1-->2)]-O-(4,6-di-O-acetyl-beta-D-galactopyranosyl)-(1-->3)]-2- acetamido-2-deoxy-alpha-D-galactopyranosyl)-(1-->3)-L-serine allyl ester, a protected glycosylserine identified as a blood group A mucin-type determinant, was synthesized for the first time in an efficient and stereocontrolled manner. Ethyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy- alpha-D-galactopyranosyl-(1-->3)-O-[(2,3,4-tri-O-benzyl-alpha-L- fucopyranosyl)-(1-->2)]-O-(4,6-di-O-acetyl-beta-D-galactopyranosyl)- (1-->3)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranos ide and N-(9-fluorenylmethoxycarbonyl)-O-[O-(2-acetamido-3,4,6-tri-O-acety l-2- deoxy-alpha-D-galactopyranosyl)-(1-->3)-O-[(2,3,4-tri-O-benzyl-alpha-L- fucopyranosyl)-(1-->2)]-O-(4,6-di-O-acetyl-beta-D-galactopyranosyl)- (1-->3)-2-acetamido-2-deoxy-alpha-D-galactopyranosyl]-(1-->3)-L-serine allyl ester were the key intermediates for the crucial glycosylation to afford the title compound.
Subject(s)
ABO Blood-Group System , Mucins/chemical synthesis , Carbohydrate Conformation , Carbohydrate Sequence , Female , Humans , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Molecular Structure , Mucins/chemistry , Ovary/chemistryABSTRACT
N,N-Dimethyl-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-(1-->3)-O- [(alpha-L-fucopyranosyl)-(1-->2)]-O-(beta-D-galactopyranosyl)-(1-->3)-O- (2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-(1-->3)-L-serine, a core I glycotetraosyl peptide structure and a predominant substructure in complex glycan-glycoproteins present in human blood group A ovarian mucin, was synthesized for the first time. The title compound was synthetically accomplished via the following key manoeuvres: regio- and stereo-controlled construction of the alpha-GalNAc-(1-->3)-Gal synthon, stereoselective glycosylation generating a alpha-GalN3-(1-->3)-Ser glycopeptide synthon and alpha-selective fucosylation towards an acceptor which was derived from glycosylation of the latter two synthons. An alternative route to that of the latter, to synthesize a fully protected equivalent of the title compound, involving the coupling of a alpha-GalNAc-(1-->3)-beta-Gal-(1-->3)-GalN3X synthon to an aglycon serine derivative, is described herein.
