Stereochemical features of Lewis acid-promoted glycosidations involving 4'-spiroannulated DNA building blocks

Tin tetrachloride-catalyzed glycosidation of persilylated nucleobases with acetate donor 6 in CH(2)Cl(2) solution followed by deprotection gave rise very predominantly to alpha-spironucleosides. These stereochemical assignments stem from the determination of NOE interactions and an X-ray crystallographic analysis of the latter product. Computational studies revealed that these results are consistent with the fact that the C5' substituent shields the beta-face of the oxonium ion involved in the coupling reaction while the C3' substituent is projected away from the alpha-underside. Attack from the more open direction is therefore kinetically favored. Entirely comparable calculations suggested that donor 19 should behave comparably. Experimentation involving this donor gave results consistent with this model although more equitable alpha/beta spironucleoside product ratios were seen when acetonitrile was employed as the reaction medium.     

Synthesis of the N-Amykitanosyl Tetramic Acid Moiety of Amycolamicin

An improved five-step synthetic route from l -fucose to an N-glycosyl l -valine methyl ester has been developed. The new route involves glycosidation of l -fucose with phenol in a β-selective manner without protection/deprotection steps and one-pot stereochemical inversion of a secondary alcohol intermediate and is superior to our previous one both in the number of steps and in overall yield. An N-glycosyl l -valine benzyl ester, prepared from l -fucose in an analogous way, has been elaborated into an N-amykitanosyl tetramic acid derivative, Li's synthetic intermediate for amycolamicin, via a four-step sequence which features the utilization of Bestmann's ylide to stereoconvergently construct an N-glycosyl tetramic acid intermediate in a single step, opening of a cyclic carbonate ring with an amine to regioselectively install a carbamate functionality, and visible light-mediated oxidative debenzylation of an N,N-dibenzyl carbamate.     

Synthetic 3-O-methylmannose-containing polysaccharides (sMMPs): design and synthesis

With the hope of mimicking the chemical and biological properties of natural 3-O-methylmannose-containing polysaccharides (MMPs), synthetic 3-O-methylmannose-containing polysaccharides (sMMPs) were designed and synthesized in a convergent manner. With little modification of the Mukaiyama glycosidation, high alpha-selectivity (>50:1 approximately >20:1) and yields (79 approximately 74%) were achieved for the key glycosidation steps. The exceptionally high alpha-selectivity observed was shown to be consequent to the selective anomerization of beta- to alpha-anomer under the glycosidation conditions. This glycosidation is well suited for a highly convergent oligosaccharide synthesis, particularly because of excellent chemical yields even when using approximately equal-sized donors and acceptors in an approximately 1:1 molar ratio. An iterative reaction sequence allowed the growing oligosaccharide to double in size after each cycle and led to an efficient synthesis of sMMP 8-, 12-, and 16-mers 18-20.     

InBr3-catalyzed cyclization of glycosides with arylamines

Glycals have served as excellent substrates in the glycosidation reactions with arylamines to construct both C–C and C–N linkages simultaneously. However, the high reactivity and moisture/alcohol-sensitivity is also responsible for several side reactions. Herein we reported that 2,3-unsaturated glycosides can be used as alternatives of glycals to take part in the corresponding glycosidation as well. Therefore, with 10% of InBr₃ or InI₃ as the catalyst, 2,3-unsaturated glycosides containing various C-1 alkoxy groups reacted with arylamines smoothly and produced the glycosidation products in moderate to good yields as a pair of diastereomers with variant diastereoselectivity.     

Concerning the origin of the high beta-selectivity of glycosidation reactions of 2-deoxy-2-iodo-glucopyranosyl trichloroacetimidates

[structure: see text] Studies on the glycosidation reactions of conformationally constrained glycosyl imidates 8a and 8b were performed to evaluate the possible involvement of "conformationally inverted" oxonium ion intermediates in glycosidation reactions with 2-deoxy-2-iodo-glucopyranosyl donors. The mechanistic implications of this study are discussed, and intermediates 23 and 24 are invoked to rationalize the observed beta-selectivities.     

Concerning a new glycoside preparation method. Synthesis of epidopodophyllotoxin-beta-D-glucopyranoside

A new method for the synthesis of glycosides is described. Epipodophyllotoxin ( 4 ) reacts with 2,3,4,6-tetra-O-acetyl-β-D -glucopyranose in the presence of BF₃-etherate at low temperature to yield tetra-O-acetyl-epipodophyllotoxin-β-D -glucopyranoside ( 6 ). This compound, which is sensitive to acid and base, can be converted into the free glucoside 8 by zinc acetate catalysed methanolysis. Glycosidation of podophyllotoxin ( 1 ) occurs under the same conditions but is associated with an inversion at C-1 of the aglycone moiety, leading also to the acetylated epi-glucoside 6 . It is assumed that the glycosidation proceeds through a common carbonium ion intermediate ( 12 ), generated from 1 and 4 respectively by the action of BF₃. The intermediate 12 is substituted by the pyranose component from the less hindered side, giving exclusively 1-epi derivatives (e.g. 6 ). The glycosidation reaction is also highly stereoselective with respect to the glycosidic linkage. The stereochemistry of this bond is determined by the configuration at C-1 of the pyranose compound employed for the glycosidation. Further experimental evidence for the proposed mechanism consists in the glycosidation of diphenylmethanol ( 14 ) to the corresponding β-D -glucoside 15 . Scope and limitation of the new glycosidiation method are briefly discussed.     

One-pot chemo-, regio-, and stereoselective double-differential glycosidation mediated by lanthanide triflates

Nuanced activation of n-pentenyl, thioglycoside, and trichloroacetimidate donors by lanthanide salts coupled with donor/acceptor matching can simplify oligosaccharide assembly. Thus, a one-pot, double-differential glycosidation process can be designed, in which an n-pentenyl acceptor-diol is chemo- and regioselectively glycosidated by using an n-pentenyl ortho ester under the agency of Yb(OTf)(3)/NIS followed by in situ addition of a 2-O-acylated trichloroacetimidate or ethyl thioglycoside to effect stereoselective glycosidation at the remaining OH.     

Synthesis of thietane nucleosides by glycosidation of thietanose derivatives with nucleobases

Thietane nucleosides were synthesized by the glycosidation of glycosyl fluoride with nucleobase.     

Über die Herstellung des Methyl-α-D-fructopyranosides und die Struktur der dabei gebildeten Orthoester

Concerning the preparation of methyl α-D -fructopyranoside and the structure of the orthoester by-products Koenigs-Knorr glycosidation (AgClO₄/Ag₂CO₃) of the easily accessible p-nitrobenzoylated fructosylchloride 7 yields mainly the protected glycoside 3 which was deacylated to the known title compound 1 . The orthoesters 15 and 16 were formed as by-products in this glycosidation whilst the analogous orthoesters 21 and 22 are formed as main products in the glycosidation (Ag₂CO₃) of the benzoylated fructosylchloride 12 . The structure of these orthoesters was deduced mainly from their spectroscopic data, from those of their derivatives 17 , 18 , 19 , 20 , 25 and 26 and by comparison of the latter with the model compounds 31 and 34 .     

C, O, S, N-苷的高效立体选择合成

研究了正氟乙酸糖苷和三甲基硅烷基糖苷醚作为糖苷给予体。在路易士酸存在时应用1-O-三氟乙酰基-2,3,4,6-四-O-苄基-α-D-吡喃葡萄糖和芳香醚合成C-芳基-D-吡喃葡萄糖苷的方法。在十分温和的条件下以81-99%的得率获得β-异构体, 这一方法被扩展到O, S, N-苷的合成。     

Microwave-assisted organic synthesis versus conventional heating. A comparative study for Fisher glycosidation of monosaccharides

The Fisher glycosidation of monosaccharides (d-glucose and d-mannose) with fatty alcohols was studied under microwave irradiation and conventional heating with strict internal temperature control using a fiber optic sensor. Surfactants were obtained in only 3 minutes under microwave at maximum power of 5 W to avoid overshoot and products decomposition. In contrast with the typical reported glycosidation methods, the reaction under conventional heating can be carried out at the same time and temperature with high conversion.     

Studies on the synthesis of landomycin A: synthesis and glycosidation reactions of L-rhodinosyl acetate derivatives

An efficient, eight-step synthesis of L-rhodinosyl acetate derivative 3 is described. The synthesis originates from methyl (S)-lactate and involves a highly stereoselective, chelate-controlled addition of allyltributylstannane to the lactaldehyde derivative 7. The beta-anomeric configuration of 3 was established with high selectivity by acetylation of the pyranose precursor with Ac(2)O and Et(3)N in CH(2)Cl(2). Preliminary studies of glycosidation reactions of 3 and L-rhodinosyl acetate 10 containing a 3-O-TES ether revealed that these compounds are highly reactive glycosidating agents and that trialkylsilyl triflates are effective glycosylation promoters. The best conditions for reactions with 15 as the acceptor involved use of diethyl ether as the reaction solvent and 0.2 equiv of TES-OTf at -78 degrees C. However, the TES ether protecting group of 10 proved to be too labile under these reaction conditions, and mixtures of 16a, 17, and 18a are obtained in reactions of 10 and 15. Disaccharide 17 arises via in situ cleavage of the TES ether of disaccharide 16a, while trisaccharide 18a results from a glycosidation of in situ generated 17 (or of 16a itself) with a second equivalent of 10. These problems were largely suppressed by using 3 with a 3-O-TBS ether protecting group as the glycosyl donor and 0.2 equiv of TES-OTf as the reaction promoter. Attempts to selectively glycosylate the C(3)-OH of diol acceptors 20 or 28 gave a 70:30 mixture of 21 and 22 in the reaction of 20 and a 43:27:30 mixture of regioisomeric trisaccharides 29 and 30 and tetrasaccharide 31 from the glycosidation reaction of 28. However, excellent results were obtained in the glycosidation of differentially protected disaccharide 34 using 1.5 equiv of 3 and 0.05 equiv of TBS-OTf in CH(2)Cl(2) at -78 degrees C. The latter step is an important transformation in the recently reported synthesis of the landomycin A hexasaccharide unit.     

Total synthesis of a diastereomer of the marine natural product clavosolide A

The first total synthesis of the reported structure of the sponge metabolite clavosolide A is described using a Prins cyclisation to assemble the tetrahydropyran core followed by manipulation of the side-chain, dimerisation and finally glycosidation.     

A stereocontrolled construction of 2-azido-2-deoxy-1,2-cis-α-galactosidic linkages utilizing 2-azido-4,6-O-benzylidene-2-deoxygalactopyranosyl diphenyl phosphates: stereoselective synthesis of mucin core 5 and core 7 structures

TMSOTf-promoted glycosidation of 2-azido-4,6-O-benzylidene-2-deoxygalactosyl diphenyl phosphates with fluorenylmethoxycarbonyl (Fmoc)-protected serine and threonine derivatives in THF/Et₂O (1:1) gave glycosyl amino acids in high yields and with excellent levels of α-selectivity (α/β=94:6–95:5). The synthetic utility of the present glycosidation method was demonstrated by a stereoselective synthesis of mucin-type glycopeptide core 5 and core 7 building blocks, which are suitable for Fmoc-based solid-phase synthesis of O-glycopeptides.     

Stereoselective glycosidations of uronic acids

Stereoselective glycosidation and disaccharide formation of uronic acids were performed with silver perchlorate in acetonitrile. The course of the reaction is controlled by intermediate nitrilium acetonitrile conjugates, which are generated in situ.     

Direct synthesis of silver/polymer/carbon nanocables via a simple hydrothermal route

High-yield silver/polymer/carbon nanocables were synthesized via a one-step simple hydrothermal route by using silver chloride and glucose as precursors. High-resolution TEM and element mapping proved that as-prepared nanocables consist of a silver nanowire core, a polymer inner shell, and a graphitic carbon outer shell. A three-step growth mechanism was proposed to explain the growth of such three-layer nanocables, i.e. the formation of silver nanowires, the glycosidation of glucose molecules on silver nanowire surface and the carbonization of the outmost glycosidation layer. We believe that reaction temperature plays the key role in the polymerization of glucose and sequent surface-carbonization.     

Iminosugar thioglycosides as glycosyl donors: a route to disaccharides with an iminosugar moiety

The iminosugar thioglycosides are used as glycosyl donors in glycosidation reactions. Thereby, iminosugar glycosides and disaccharide analogues with an iminosugar moiety are prepared. The yields are high and the method is stereoselective.     

The total synthesis of (+)-payllanthostatin 2

The first total synthesis of the antitumor glycoside phyllanthostatin 2 (3) is reported utilizing a Mitsunobu glycosidation protocol to unite the disaccharide and aglycone moieties.     

A crystallization-induced stereoselective glycosidation reaction in the synthesis of the anticancer drug etoposide

The anticancer drug etoposide, 1, is prepared in 79% overall yield from readily available 4'-demethyl-4-epipodophyllotoxin, 3, and 4, 6-O-ethylidene-2,3-O-dibenzyl-D-glucose, 4, via a crystallization-induced stereoselective glycosidation reaction followed by catalytic hydrogenation.     

Total synthesis of stevioside

Steviol 2 was transformed into stevioside 1 by applying the stereoselective methods of glycosidation.