Glycosyl trifluoroacetimidates. 2. Synthesis of dioscin and xiebai saponin I

Two trisaccharide steroidal saponins, dioscin (1) and Xiebai saponin I (2) with various bioactivities, were efficiently synthesized using the newly developed glycosyl N-phenyl trifluoroacetimidates (10-13) as glycosylation donors. Thus, dioscin was synthesized in five steps and a 33% overall yield from diosgenin and glycosyl trifluoroacetimidates (10 and 11). Xiebai saponin I was synthesized in eight steps and a 32% overall yield from laxogenin and glycosyl trifluoroacetimidates (10, 12, and 13), whereupon, the rare steroid laxogenin was prepared from diosgenin in four steps and an overall 69% yield. All the glycosylation reactions involved in the present syntheses demonstrated that glycosyl trifluoroacetimidates were successful donors comparable to the corresponding glycosyl trichloroacetimidates.     

N-糖基硫代亚脲基—(硫代)磷酰胺二芳基和二烷基酯的合成

二芳氧基磷酰肼(2a，2b)或二乙氧基硫代磷酰肼(4)与糖基异硫氰酸酯(5a-5b) 反应，生成相应的N-糖基硫代亚脲基—磷酰胺二芳基酯(6a-6d,7a-7d)和N-糖基硫 代亚脲基—硫代磷酰胺二乙基酯(8a-8d)．     

Direct and stereoselective synthesis of alpha-linked 2-deoxyglycosides

alpha-Linked 2-deoxyglycosides were conveniently obtained by employing a glycosyl donor having a participating ( S)-(phenylthiomethyl)benzyl moiety at C-6, whereas 2,6-dideoxy-alpha-glycosides could be prepared by BF 3.Et 2O-promoted activation of allyl glycosyl donors.     

Synthesis of glycosylthiols and reactivity studies

The acid-catalyzed reaction of 1,2-anhydro-3,4,6-tri-O-benzyl-α-d-glucopyranose (7) as glycosyl donor with bis-trimethylsilyl sulfide as acceptor affords the α-thiol. Hence, this sterically hindered S-nucleophile as acceptor should provide with O-glycosyl trichloroacetimidates as glycosyl donors that have nonparticipating groups at C-2, glycosylthiols with the thiol group in axial position. This was confirmed for various donors (4, 16-19) with the exception of the corresponding mannosyl donor (20). However, powerful participating groups at C-2 of the donor (23-28) governed the anomeric selectivity.     

Linear synthesis of a protected H-type II pentasaccharide using glycosyl phosphate building blocks.

A linear synthesis of a fully protected H-type II blood group determinant pentasaccharide utilizing glycosyl phosphate and glycosyl trichloroacetimidate building blocks is reported. Envisioning an automated solid-phase synthesis of blood group determinants, the utility of glycosyl phosphates in the stepwise construction of complex oligosaccharides, such as the H-type II antigen, is demonstrated. Installation of the central glucosamine building block required the screening of a variety of nitrogen protecting groups to ensure good glucosamine donor reactivity and protecting group compatibility. The challenge to differentiate C2 of the terminal galactose in the presence of other hydroxyl and amine protecting groups prompted us to introduce the 2-(azidomethyl)benzoyl group as a novel mode of protection for carbohydrate synthesis. The compatibility of this group with traditionally employed protecting groups was examined, as well as its use as a C2 stereodirecting group in glycosylations. The application of the 2-(azidomethyl)benzoyl group along with a systematic evaluation of glycosyl donors allowed for the completion of the pentasaccharide and provides a synthetic strategy that is expected to be generally amenable to the solid support synthesis of blood group determinants.     

Constituents of Crinoidea. 5. Isolation and structure of a new glycosyl inositolphosphoceramide-type ganglioside from the feather star Comanthina schlegeli

A new glycosyl inositolphosphoceramide-type ganglioside, CSP2, was obtained from the polar lipid fraction of the chloroform/methanol extract of the feather star Comanthina schlegeli together with a known same type of ganglioside CJP2. The structure of this ganglioside has been determined on the basis of chemical and spectroscopic evidence to be 9-O-methyl-(N-acetyl-alpha-D-neuraminosyl)-(2-->3)-inositolphosphoceramide, which contains C(16)-sphingosine and C(22:0)-, C(24:0)-fatty acid as major component. This is the first report on the isolation and structural elucidation of a glycosyl inositolphosphoceramide-type ganglioside possessing N-acetyl-neuraminic acid (NeuAc) residue.     

Analytical application of acetate anion in negative electrospray ionization mass spectrometry for the analysis of triterpenoid saponins--ginsenosides

Ginsenosides containing different numbers of glycosyl groups can be easily differentiated based on the formation of characteristic ginsenoside-acetate adduct anions and deprotonated ginsenosides generated by electrospray ionization (ESI) of methanolic solutions of ginsenosides (M) and ammonium acetate (NH4OAc). Ginsenosides containing two glycosyl groups gave a characteristic mass spectral pattern consisting of [M+2OAc]2-, [M-H+OAc]2- and [M-2H]2- ions with m/z values differing by 30 Th, while this mass spectral pattern was not observed for ginsenosides containing one glycosyl group. Formation of [M+2OAc]2- was influenced by the chain length of glycosyl groups and was used to differentiate the ginsenosides containing different combinations of monosaccharide and disaccharide units in the glycosyl groups. Under identical collisional activation conditions, [M+OAc]-, [M-H+OAc]2- and [M+2OAc]2- underwent proton abstractions predominantly to generate [M-H]-, [M-2H]2- and [M-H+OAc]2- ions, respectively. The ion intensity ratios, I[M-H](-/I) [M+OAc]-, I[M-2H](2-/I) [M-H+2OAc]2- and I[M-H+OAc](2-/I) [M+OAc]2-, being sensitive to the structural differences of ginsenosides, could differentiate the isomeric ginsenosides, including (i) Rf, F11 and Rg1, (ii) Rd and Re, and (iii) Rb2 and Rc. Additionally, NH4OAc was found to enhance the sensitivity of detection of ginsenosides in the form of [M-H]- down to the femtomole level.     

O-(1-Phenyl-1H-tetrazol-5-yl) Glycosides: Alternative synthesis and transformation into glycosyl fluorides

A number of new glycosyl donors, O-(1-phenyl-1H-tetrazol-5-yl) glycosides, are prepared from the corresponding hemiacetals, commercially available 5-chloro-1-phenyl-1H-tetrazole ( 2 ), and tetrabutylammonium fluoride (Bu₄NF) in either THF or DMF. The mild reaction conditions are compatible with a variety of protecting groups. The glycosyl donors are treated with hydrogen fluoride-pyridine complex (HF·py) to rapidly provide glycosyl fluorides in good-to-excellent yields, apparently by a (single or double) S_N2 mechanism as studied by both ¹H- and ¹⁹F-NMR spectroscopy. Under acidic conditions, glycosyl fluorides equilibrate partially or completely, equilibration requiring a large excess of HF · py.     

2-Deoxy-2-iodo- and 2-deoxy-2-bromo-alpha-glucopyranosyl trichloroacetimidates: highly reactive and stereoselective donors for the synthesis of 2-deoxy-beta-glycosides

[formula: see text] 2-Deoxy-2-iodo- and 2-deoxy-2-bromoglucopyranosyl trichloroacetimidates 8-10 and 22 are extremely useful precursors of 2-deoxy-beta-glycosides. These reactive glycosyl donors undergo highly stereoselective glycosidation reactions at -78 degrees C with a range of glycosyl acceptors using TBS-OTf as the activating agent. beta-Glycosides are obtained with > or = 19:1 selectivity in six of the seven examples reported herein.     

Synthetic Studies on Sialoglycoconjugates 16: α-Predominant Glycoside Synthesis of N-Acetylneuraminic Acid With the Primary Hydroxyl Group in Carbohydrates Using Dimethyl(Methylthio)Sulfonium Triflate as a Glycosyl Promoter

ABSTRACT

Coupling of the primary hydroxyl group in the suitably protected 2-(trimethylsilyl)ethyl glycosides of D-glucopyranose (3), N-acetyl-D-glucosamine (7), N-acetyl-D-galactosamine (9), D-lactose (10), and N-acetylneuraminic acid (11), with methyl (methyl 5-acetamido-4, 7,8, 9-tetra-O-acetyl-3, 5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate (12) as the glycosyl donor in acetonitrile in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) as a glycosyl promoter and molecular sieves 3A, gave predominantly the corresponding α-glycosides 13, 15, 17, 25, and 29 of N-acetylneuraminic acid in 43-71% yields, respectively, together with the ß-glycosides (13-24%).     

The Synthesis of the 2′′- and 2′′′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2′′ or C-2′′′ have been synthesized in [2+2] block syntheses. O-(2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-3,6-di-O-benzyl-1,2-di-O-acetyl-β-D-glucopyranose (6), prepared from the respective orthoester, was coupled to the glycosyl acceptor 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside. In the resulting tetrasaccharide 8, the only ester group was removed and replaced by a xanthate which was reduced in a Barton-McCombie reaction to afford the 2′′-deoxygenated tetrasaccharide 12. For the synthesis of a 2′′′-deoxygenated derivative, a maltose building block was assembled from two monosaccharides. The key building block was ethyl 2,3,6-tri-O-benzyl-1-thio-β-D-glucopyranoside (14) which was used i) as a glycosyl acceptor in a phenylselenyl chloride mediated coupling reaction with tri-O-benzyl-glucal and ii) after the first coupling as a glycosyl donor to react with glycosyl acceptor 7 to give tetrasaccharide 18. The phenylselenyl group was reduced with tributyltin hydride on the disaccharide level. Deprotection of 18 furnished the 2′′′-deoxy-maltosyl-(1→4)-trehalose 20.     

Stereoselective direct glycosylation with anomeric hydroxy sugars by activation with phthalic anhydride and trifluoromethanesulfonic anhydride involving glycosyl phthalate intermediates

An efficient direct one-pot glycosylation method with anomeric hydroxy sugars as glycosyl donors employing phthalic anhydride and triflic anhydride as activating agents has been developed. Thus, highly stereoselective beta-mannopyranosylations were achieved by the reaction of 2,3-di-O-benzyl-4,6-O-benzylidene-D-mannopyranose (2) with phthalic anhydride in the presence of DBU at room temperature followed by sequential addition of DTBMP and Tf2O and glycosyl acceptors to the reaction mixture at -78 degrees C in one-pot. Stereoselective alpha-glucopyranosylations with 2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranose (25) and other glycosylations with glucopyranoses and mannopyranoses having tetra-O-benzyl- and tetra-O-benzoyl protecting groups were also possible by utilizing the present one-pot glycosylation protocol. The possible mechanism for the beta-mannosylation with 2 was proposed based on the NMR study, in which alpha-mannosyl phthalate 55alpha and alpha-mannosyl triflate 59 were detected as intermediates. The versatility and efficiency of the present glycosylation methodology, especially those of the beta-mannopyranosylation protocol, were readily demonstrated by the efficient synthesis of protected beta-(1-->4)-D-mannotriose 62 and beta-(1-->4)-D-mannotetraose 67 with perfect beta-stereoselectivity.     

Reactions of difluoroenoxysilanes with glycosyl donors: synthesis of difluoro-C-glycosides and difluoro-C-disaccharides

Difluoroenoxysilanes, prepared from acylsilanes and trifluoromethyltrimethylsilane under fluoride activation, were glycosylated with some glycosyl donors (acylglycosides, glycals) to yield difluoro-C-glycosides with a difluoromethylene group in the place of the anomeric oxygen. This reaction strongly depends on the substituent in the 2-position of the glycosyl donor. Application of this methodology to a xylose-derived acylsilane led to the formation of difluoro-C-disaccharides as an isosteric O-glycosyl mimetic.     

1-Benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride: a potent combination of shelf-stable reagents for the low-temperature conversion of thioglycosides to glycosyl triflates and for the formation of diverse glycosidic linkages

The combination of 1-benzenesulfinyl piperidine (BSP) and trifluoromethanesulfonic anhydride (Tf(2)O) forms a new, powerful, metal-free thiophile that can readily activate both armed and disarmed thioglycosides, via glycosyl triflates, in a matter of minutes at -60 degrees C in dichloromethane, in the presence of 2,4,6-tri-tert-butylpyrimidine (TTBP). The glycosyl triflates are rapidly and cleanly converted to glycosides, upon treatment with alcohols, in good yield and selectivity.     

Internal degrees of freedom,structural motifs,and conformational energetics of the 5'-deoxyadenosyl radical: implications for function in adenosylcobalamin-dependent enzymes. A computational study

The potential energy surface of the free 5'-deoxyadenosyl radical in the gas phase is explored using density functional and second-order M?ller-Plesset perturbation theories with 6-31G(d) and 6-31++G(d,p) basis sets and interpreted in terms of attractive and repulsive interactions. The 5',8-cyclization is found to be exothermic by approximately 20 kcal/mol but kinetically unfavorable; the lowest cyclization transition state (TS) lies about 7 kcal/mol higher than the highest TS for conversion between most of the open isomers. In open isomers, the two energetically most important attractive interactions are the hydrogen bonds (a) between the 2'-OH group and the N3 adenine center and (b) between the 2'-OH and 3'-OH groups. The relative ribose-adenine rotation about the C1'-N9 glycosyl bond in a certain range changes the energy by as much as 10-15 kcal/mol, the origin being (i) the repulsive 2'-H.H-C8 and O1'.N3 and (ii) the attractive 2'-OH.N3 ribose-adenine interactions. The hypothetical synergy between the glycosyl rotation and the Co-C bond scission may contribute to the experimentally established labilization of the Co-C bond in enzyme-bound adenosylcobalamin. The computational results are not inconsistent with the rotation about the C1'-N9 glycosyl bond being the principal coordinate for long-range radical migration in coenzyme B(12)-dependent enzymes. The effect of the protein environment on the model system results reported here remains an open question.     

Glycosidation with a disarmed glycosyl iodide: promotion and scope

[reaction: see text] Glucuronyl iodide 1 has been studied in detail as a "disarmed" glycosyl donor. In a model reaction, using N-iodosuccinimide (NIS) as a promoter and 2-phenylethanol as acceptor, best results were obtained using NIS with I(2), followed by trimethylsilyltrifluoromethanesulfonate (TMSOTf). When a series of primary and secondary alcohols was glycosylated using these conditions, yields of 60-83% of beta-glucuronides were obtained. Various "nonheavy" metal salts also effectively catalyzed the model reaction but led to significant amounts of alpha-product with less reactive secondary alcohols.     

A new, efficient glycosylation method for oligosaccharide synthesis under neutral conditions: preparation and use of new DISAL donors

Efficient, stereoselective glycosylation methods are required for the synthesis of complex oligosaccharides as tools in glycobiology. All glycosylation methods, which have found wide acceptance, rely on Lewis acid activation of glycosyl donors prior to glycosylation. Here, we present a new and efficient method for glycosylation under neutral or mildly basic conditions. Glycosides of methyl 2-hydroxy-3,5-dinitrobenzoate (DISAL) and its para regioisomer, methyl 4-hydroxy-3,5-dinitrobenzoate, were prepared by nucleophilic aromatic substitution. In a first demonstration of their potential as glycosyl donors, stereospecific glycosylation of methanol was achieved. In the glycosylation of more hindered alcohols, the beta-donor proved more reactive, and alpha-glucosides were predominantly formed. Glycosylation of protected monosaccharides, with free 6-OH or 3-OH, proceeded smoothly in 1-methyl-2-pyrrolidinone (NMP) at 40-60 degrees C in the absence of Lewis acids and bases in good to excellent yields. Glycosylation of 3-OH gave the alpha-linked disaccharide only.     

Electrochemical generation of glycosyl triflate pools

Glycosyl triflates, which serve as important intermediates in glycosylation reactions, were generated and accumulated by the low-temperature electrochemical oxidation of thioglycosides such as thioglucosides, thiogalactosides, and thiomannosides in the presence of tetrabutylammonium triflate (Bu(4)NOTf) as a supporting electrolyte. Thus-obtained solutions of glycosyl triflates (glycosyl triflate pools) were characterized by low-temperature NMR measurements. The thermal stability of glycosyl triflates and their reactions with glycosyl acceptors were also examined.     

Alternative Syntheses of (l→3)-β-D-Galacto-Oligosaccharides

ABSTRACT

Galactosyl halides bearing different substituents at O-3 [i.e. acetyl (15), benzoyl (14), benzyl (3), bromoacetyl (12), and the 2, 3, 4, 6-tetra-O-benzoyl-β-D-galactopyranosyl group (17)] have been prepared, and used to study the stereoselectivity of the coupling reaction to position O-3 of different galactose derivatives [i.e. methyl 2, 4, 6-tri-O-acetyl-(9) and 2, 4, 6-tri-O-benzoyl-β-D-galactopyranoside (7), l, 2, 4, 6-tetra-O-benzoyl-β-D-galactose (6) and O-(2, 4, 6-tri-O-benzoyl-β-D-galactopyranosyl)-(1→3)-β-D-galactose (33)], as well as to benzoic acid. In more polar solvents, using silver trifluoro-methanesulfonate as the promoter, a higher proportion of β-linked products was formed, whereas with silver perchlorate as the promoter the α-linked product predominated. Under basic conditions, applied to prevent anomerisation of 1-O-benzoylated nucleophiles 6 and 33, no orthoesters were found as end products. Under those conditions, a better overall yield of the β-(l→3)-linked galactotriose 31 was obtained by condensation of die disaccharide glycosyl donor 17 and the monosaccharide glycosyl acceptor 6 than by condensation of 14 and 33. The disaccharide glycosyl chloride 17 was obtained in 75% yield by the cleavage of the corresponding methyl glycoside with dichloromethyl methyl ether.     

Alpha-N-acetylmannosamine (ManNAc) synthesis via rhodium(II)-catalyzed oxidative cyclization of glucal 3-carbamates

[reaction: see text] Glucal 3-carbamates 1 and 7 underwent oxidative cyclization with iodobenzene diacetate or iodosobenzene in the presence of Rh2(OAc)4, providing mannosamine 2-N,3-O-oxazolidinones. With iodosobenzene, incorporation of 4-penten-1-ol provided a readily separable anomeric mixture of n-pentenyl glycosides, with the anomers exhibiting pronounced differences in reactivity as glycosyl donors. N-acylation of the sugar oxazolidinones led to alpha-selective glycosyl donors for the elaboration of various 2-mannosamine frameworks. Alternatively, the anomeric n-pentenyl glycosides of N-Cbz 2-mannosamine oxazolidinones were converted separately to oxazolidinone-opened derivatives 28alpha and 28beta. These served as stereoconvergent glycosyl donors, and the alpha-linked products were readily advanced to a variety of N-acetylmannosamine (ManNAc) frameworks, using an intramolecular O-->N acetyl transfer as the final step.