Significant Substituent Effect on the Anomerization of Pyranosides: Mechanism of Anomerization and Synthesis of a 1,2‐cis Glucosamine Oligomer from the 1,2‐trans Anomer

Aminoglycosides containing a 2,3‐trans carbamate group easily undergo anomerization from the 1,2‐trans glycoside to the 1,2‐cis isomer under mild acidic conditions. The N‐substituent of the carbamate has a significant effect on the anomerization reaction; in particular, an N‐acetyl group facilitated rapid and complete α‐anomerization. The differences in reactivity due to the various N‐substituents were supported by the results of DFT calculations; the orientation of the acetyl carbonyl group close to the anomeric position was found to contribute significantly to the directing of the anomerization reaction. By exploiting this reaction, oligoaminoglycosides with multiple 1,2‐cis glycosidic bonds were generated from 1,2‐trans glycosides in a one‐step process.     

Pyranosides with 2,3‐trans Carbamate Groups: Exocyclic or Endocyclic Cleavage Reaction?

Pyranosides with 2,3‐trans carbamate groups exhibit high 1,2‐cis selectivity in glycosylation reactions. Using glycosyl donors with N‐benzyl 2,3‐trans carbamate groups, an anti‐Helicobacter pylori oligosaccharide was synthesized in an efficient manner. Moreover, pyranosides with 2,3‐trans carbamate groups readily undergo anomerization from the β to the α configuration under mild acidic conditions via endocyclic cleavage. Acyclic cations generated during the endocyclic cleavage reaction were captured using reduction and intramolecular Friedel–Crafts reaction. By exploiting this anomerization, multiply aligned 1,2‐trans glycosyl bonds can be transformed to 1,2‐cis glycosyl bonds in a single operation.     

Investigations of glycosylation reactions with 2-N-acetyl-2N,3O-oxazolidinone-protected glucosamine donors

NIS/AgOTf-promoted glycosylations with ethyl 2,3-N,O-carbonyl-2-deoxy-1-thio-beta-D-glucopyranoside donors can be performed with either alpha- or beta-selectivity by tuning the reaction conditions. Small amounts of AgOTf (0.1 equiv) and short reaction times give beta-selectivity, whereas 0.4 equiv of AgOTf and prolonged reaction times afford alpha-linked products. NMR-monitored glycosylation and anomerization experiments show initial formation of exclusively the beta-linkage, which anomerizes, through an intramolecular mechanism involving an endocyclic C-O bond cleavage, to the alpha-linkage.     

Substituent effects in endocyclic cleavage-recyclization anomerization reaction of pyranosides

Pyranosides with 2,3-trans carbamate or 2,3-trans carbonate groups are anomerized under mild acidic conditions via endocyclic cleavage reaction. In order to understand the nature of the anomerization reaction via the endocyclic cleavage-recyclization process, the substituent effects at various positions were investigated.     

Synthesis of tertiary and quaternary stereogenic centers: a diastereoselective tandem reaction sequence combining Mukaiyama and free radical-based allylation

Reported herein is a strategy employing a Mukaiyama reaction in tandem with a free radical-based allyl transfer reaction for the elaboration of functionalized tertiary and quaternary centers. The appropriate choice of alcohol-protecting group on the starting alpha-methyl-beta-hydroxyaldehyde and the nature of the Lewis acid used in the Mukaiyama reaction provided access to 3,4-anti and 3,4-syn aldolization products, precursors of the free-radical allylation reaction. After migration or exchange of the Lewis acid, the allyl transfer reaction with allyltributylstannane is then performed by taking advantage of the endocyclic effect, leading to the 2,3-anti relative stereochemistry. Importantly, (13)C NMR studies of the chelated intermediates are also reported and provide additional support for the endocyclic effect. In some cases, the remarkable reactivity of the aluminum-based Lewis acids allowed the use of allyltrimethylsilane, an interesting reagent from an ecological standpoint. The isolation of a key intermediate is also indicative of an atom transfer mechanism when the silicon-based reagent is employed.     

S-benzoxazolyl as a stable protecting moiety and a potent anomeric leaving group in oligosaccharide synthesis

As a part of a program for developing new versatile building blocks for stereoselective glycosylation and convergent oligosaccharide synthesis, we demonstrated that S-benzoxazolyl (SBox) glycosides are stable toward major protecting group manipulations employed in carbohydrate chemistry. On the other hand, they can be glycosidated under relatively mild reaction conditions to afford either 1,2-trans or 1,2-cis-linked disaccharides. Selective and chemoselective activations of the SBox moiety were also proved to be feasible, which was demonstrated by synthesizing a number of oligosaccharide sequences.     

Reagent-controlled stereoselective synthesis of lignan-related tetrahydrofurans

The reaction of ring-closing metathesis-derived cyclic allylsiloxanes 3 with aldehydes in the presence of a Lewis acid gives 2,3,4-trisubstituted tetrahydrofurans related to the furanolignan family of natural products. The reactions proceed with complete 3,4-trans stereoselectivity, whereas the C-2 stereochemistry depends on both the aldehyde and Lewis acid used. When boron trifluoride etherate is used with aliphatic or electronically neutral aryl aldehydes, the reactions favor the production of the 2,3-cis isomer 8, whereas electron-rich aryl aldehydes lead to the 2,3-trans isomer 9 by Lewis acid-mediated isomerization of the kinetically favored cis isomer. The isomerization can be avoided by use of TMSOTf as a promoter, and hence, the stereochemistry can be tuned by appropriate choice of reagent. Cleavage of the pendant 3-ethenyl group installs the 3-hydroxymethyl group common to the furanolignans.     

Evidence for Endocyclic Cleavage of Conformationally Restricted Glycopyranosides

2,3‐trans‐carbamate‐ and ‐carbonate‐carrying pyranosides were very easily anomerised from the β to the α direction in the presence of a Lewis acid compared to other pyranosides. This reaction is caused by endocyclic cleavage of the pyranosides. Evidence for endocyclic cleavage of conformationally restricted pyranosides in the chair form was obtained by intra‐ and intermolecular Friedel–Crafts reactions, chloride addition, and reduction of the generated cation. On the other hand, pyranosides with the distorted conformation were never cleaved in an endocyclic manner.     

Photoinitiated Thiol−Ene Reactions of Various 2,3‐Unsaturated O‐, C‐ S‐ and N‐Glycosides – Scope and Limitations Study

The photoinitiated thiol?ene addition reaction is a highly stereo‐ and regioselective, and environmentally friendly reaction proceeding under mild conditions, hence it is ideally suited for the synthesis of carbohydrate mimetics. A comprehensive study on UV‐light‐induced reactions of 2,3‐unsaturated O‐, C‐, S‐ and N‐glycosides with various thiols was performed. The effect of experimental parameters and structural variations of the alkenes and thiols on the efficacy and regio‐ and stereoselectivity of the reactions was systematically studied and optimized. The type of anomeric heteroatom was found to profoundly affect the reactivity of 2,3‐unsaturated sugars in the thiol?ene couplings. Hydrothiolation of 2,3‐dideoxy O‐glycosyl enosides efficiently produced the axially C2‐S‐substituted addition products with high to complete regioselectivity. Moderate efficacy and varying regio‐ and stereoselectivity were observed with 2,3‐unsaturated N‐glycosides and no addition occurred onto the endocyclic double bond of C‐glycosides. Upon hydrothiolation of 2,3‐unsaturated S‐glycosides, the addition of thiyl radicals was followed by elimination of the thiyl aglycone resulting in 3‐S‐substituted glycals.     

Propargyl/methyl furanosides as potential glycosyl donors

Transfuranosylations are not well studied though many similar studies exist for transpyranosylation; herein, we report that propargyl/methyl D-ribf- and D-lyxf- give only 1,2-trans glycosides whereas D-araf- and D-xylf- result in a mixture of 1,2-trans and 1,2-cis glycosides; observed facts are rationalised by computational studies.     

1,2和1,3-缩水内醚糖衍生物的制备, 构象及其糖苷化反应

吡喃糖的1,2-及1,3-缩水内醚苄醚由相应的吡喃糖的C-2氧负离子(对1,3-缩水内醚是C-3氧负离子)与连有氯原子的C-1经分子内关环反应而制备, 而有些吡喃糖的1,2-缩水内醚苄醚是由相应的吡喃糖的C-1氧负离子与连有对甲苯磺酰氧基的C-2经分子内关环(倒关环)反应而得。呋喃糖的1,2-缩水内醚苄醚只能用倒关环法合成。1,2-(或1,3-)缩水内醚糖的开环反应通常给出1,2-反式连接(对1,3缩水内醚是1,3反式连接)的糖苷键。1,2-及1,3-缩水内醚糖的构象分析是通过^1H NMR测定及分子力学计算的方法而完成的。     

Lewis acid-promoted rearrangement of 2,3-epoxy alcohol derivatives: stereochemical control and selective formation of two types of chiral quaternary carbon centers from the single carbon skeleton

The Lewis acid-promoted rearrangement of 2,2,3,3-tetrasubstituted 2,3-epoxy alcohols with several kinds of protecting groups was investigated. When SnCl4 is used as a Lewis acid, the reaction proceeds in a regio- and stereo-controlled manner to afford two types of carbonyl compounds selectively from a single 2,3-epoxy alcohol only by changing the protecting group of the alcohol. The method was then applied to the formation of two types of acyclic and cyclic quaternary carbon centers from the single compound in optically active forms.     

应用量子化学反应性指数研究频哪醇重排反应

1,2-二醇类化合物的频哪醇重排反应是经典的化学重排反应。无环的或环状的1,2-二醇类化合物在质子酸或路易斯酸的作用下会重排发生取代基的1,2-迁移,其产物往往伴随不同基团的迁移而生。但是,主产物取决于二羟基相连接的碳原子上取代基的空间架构和性质。本文采用净亲电指数(Multiphilic index)和Wiberg键级等量子化学反应性指数来定量描述1,2-二醇类化合物的频哪醇重排反应机理,并依此作为预测频哪醇反应主产物的依据。     

An alternative proposal for the mode of inhibition of glycosidase activity by polyhydroxylated piperidines,pyrrolidines and indolizidines: implications for the mechanism of action of some glycosidases

It is proposed that polyhydroxylated alkaloids inhibit glycosidase activity by a mechanism which suggests that the enzyme-catalysed hydrolysis of some glycosides may proceed by cleavage of the endocyclic (ring) carbon-oxygen bond, rather than the exocyclic (anomeric) carbon-oxygen bond.     

Significant solvent effect in anomerization reaction of pyranosides with 2,3-trans carbamate and carbonate

A pronounced solvent effect was observed in the anomerization reaction of pyranosides carrying 2,3-trans carbamate or carbonate. While significant anomerization from the β- to α-direction was observed in CH₃CN, none was observed in ether.     

Impact of Lewis acids on Diels-Alder reaction reactivity: a conceptual density functional theory study

Density functional theory (DFT) and conceptual/chemical DFT studies are carried out in this work for the normal electron demand Diels-Alder reaction between isoprene and acrolein to compare chemical reactivity and regioselectivity of the reactants in the absence and presence of Lewis acid (LA) catalysts. A cyclic coplanar structure of acrolein-LA complex has been observed and the natural bond orbital analysis has been employed to interpret the interaction between acrolein and LAs. Reactivity indices from frontier molecular orbital energies are proved to be adequate and efficient to evaluate the catalytic property of LAs. Linear relationships have been discovered among the bond order, bond length, catalytic activation, and chemical reactivity for the systems concerned. The validity and applicability of maximum hardness principle, minimum polarizability principle, and minimum electrophilicity principle are examined and discussed in the prediction of the major regioselective isomer and the preferred reaction pathway for the reactions in the present study.     

Glycosidation-anomerisation reactions of 6,1-anhydroglucopyranuronic acid and anomerisation of beta-D-glucopyranosiduronic acids promoted by SnCl(4)

The reaction of silylated nucleophiles with 6,1-anhydroglucopyranuronic acid (glucuronic acid 6,1-lactones) catalysed by tin(IV) chloride provides 1,2-trans or 1,2-cis (deoxy)glycosides in a manner dependent on the donor structure. The alpha-glycoside was obtained for reactions of the donor with the 2-acyl group and 2-deoxydonors, whereas the 2-deoxy-2-iodo donor gave the beta-glycoside. Experimental evidence shows that when 1,2-cis-glycoside formation occurs, the anomerisation of initially formed 1,2-trans-glycosides catalysed by SnCl(4) is possible. The anomerisation of beta-D-glucopyranosiduronic acids was found to be faster, in some cases, than anomerisation of related beta-D-glucopyranosiduronic acid esters and beta-D-glucopyranoside derivatives and the rates are dependent on the structure of the aglycon. Moreover, the rates of anomerisation of beta-D-glucopyranuronic acid derivatives can be qualitatively correlated with rates of hydrolysis of beta-D-glucopyranosiduronic acids. Mechanistic possibilities for the reactions are considered.     

A theoretical study of imine-ene reaction influencing factors

Potential energy surfaces of the imine-ene reaction between methanimine and propene have been calculated using restricted and unrestricted density functional theory at the B3LYP level. The results show that a concerted mechanism with an exo configuration for lone pair electrons transition structure is more favourable for the intermolecular bare imine-ene reaction. In addition, the C-C bond formation and the migration of the propene α-hydrogen occur simultaneously. The promoting effect of seventeen Lewis acids was also studied. When a Lewis acid is used as a promoter, the corresponding activation and reaction energies decline greatly compared to those of the bare imine-ene reaction. A good correlation (R(2) > 0.9) was found between the activation barriers and the polar character of the transition states. Lewis acids and electron-withdrawing substituents on methanimine were proven to facilitate the imine-ene reaction, whereas electron-donating groups, conjugated groups or a bulky group hinders the reaction. The steric factor is the most unfavourable. The reactivity indices defined by the conceptual density functional theory were also studied and there is a good correlation between the activation barrier and electrophilicity. Frontier molecular orbital theory gives a good explanation for the above results.     

Facile synthesis of unusual glycosyl carbamates and amino acid glycosides from propargyl 1,2-orthoesters as glycosyl donors

Propargyl 1,2-O-orthoesters are exploited for the synthesis of 1,2-trans O-glycosides of protected amino acids. N-Fmoc- and N-Cbz protected serine/threonine - benzyl/methyl esters reacted well with glucosyl-, galactosyl-, mannosyl- and lactosyl- derived propargyl 1,2-orthoesters affording respective 1,2-trans glycosides in good yields under AuBr(3)/4 ? MS Powder/CH(2)Cl(2)/rt. t-Boc serine derivative gave serine 1,2-orthoester and glycosyl carbamate. Optimized conditions enabled preparation of new glycosyl carbamates from N-Boc protected amines in a single step using gold catalysts and propargyl 1,2-orthoesters in excellent yields.     

Frustrated Lewis Pair Mediated 1,2-Hydrocarbation of Alkynes

Frustrated Lewis pair (FLP) chemistry enables a rare example of alkyne 1,2-hydrocarbation with N-methylacridinium salts as the carbon Lewis acid. This 1,2-hydrocarbation process does not proceed through a concerted mechanism as in alkyne syn-hydroboration, or through an intramolecular 1,3-hydride migration as operates in the only other reported alkyne 1,2-hydrocarbation reaction. Instead, in this study, alkyne 1,2-hydrocarbation proceeds by a novel mechanism involving alkyne dehydrocarbation with a carbon Lewis acid based FLP to form the new C−C bond. Subsequently, intermolecular hydride transfer occurs, with the Lewis acid component of the FLP acting as a hydride shuttle that enables alkyne 1,2-hydrocarbation.