Fluorescence modification of Gb3 oligosaccharide and rapid synthesis of oligosaccharide moieties using fluorous protective group

The use of the bisfluorous chain-type propanoyl (Bfp) group as a fluorous protective group made it possible to rapidly synthesize the Gb2 and Gb3 oligosaccharide derivatives by a simple fluorous-organic extraction purification. Furthermore, the fluorescence-labeled Gb2 and Gb3 oligosaccharides were prepared as a potential Vero Toxins detecting reagent.     

Cap-and-tag solid phase oligosaccharide synthesis

A new "cap-and-tag" strategy is applied to solid phase oligosaccharide synthesis. Acetyl-capping and fluorous-tagging allowed for the facile separation of the desired F-tagged oligosaccharide from the acetyl-capped deletion sequences using fluorous solid phase extraction. To illustrate this approach, a protected Glc-beta-(1-->6)-Man-alpha-(1-->6)-Glc-beta-1-->pentenyl trisaccharide was synthesized.     

Rapid oligosaccharide synthesis using a fluorous protective group

The Bfp-OH, a novel fluorous protecting reagent, was able to be easily prepared. The Bfp group was readily introduced to a carbohydrate, removed in high yield, and recyclable after cleavage. The use of the Bfp group made it possible to synthesize a pentasaccharide by minimal column chromatography purification. Each synthetic intermediate was able to be easily purified only by simple fluorous-organic solvent extraction and monitored by TLC, NMR, and MS.     

Towards oligosaccharide library synthesis by fluorous mixture method

The synthesis of an oligosaccharide library by a fluorous tag method is reported here. Several acceptors and donors were mixed and glycosylated. The reaction mixture was purified by chromatography over fluorous HPLC to provide disaccharides in order of increasing fluorine content of the tag. This method could be applied to oligosaccharide libraries consisting of two sets of structural isomers.     

Mono- vs. di-fluorous-tagged glucosamines for iterative oligosaccharide synthesis

Fluorous-tagged protecting groups are attractive tools for elongating carbohydrate chains in oligosaccharide synthesis. To eliminate the accumulation of failed sequences during automated oligosaccharide synthesis conditions, an additional C₈F₁₇ ester derived protecting group was attached to the glycosyl donor to better retain the desired doubly tagged glycosylation product on fluorous solid-phase extraction (FSPE) cartridges. Initial studies show that the double-fluorous-tagging strategy offers a robust enough separation using a commercial FSPE cartridge using simple gravity filtration to separate the desired product from the singly fluorous-tagged starting materials and their decomposition products. In addition, removal of the fluorous acetate and its by-products after sodium methoxide treatment and neutralization required only dissolution of the desired sugar in toluene and subsequent removal of the toluene layer from the denser fluorous by-products.     

Practical heavy fluorous tag for carbohydrate synthesis with minimal chromatographic purification

A practical heavy fluorous tag 5 bound to a benzylic linker was prepared and applied to carbohydrate synthesis. The fluorous tag 5 was readily introduced to the desired hydroxyl group and carboxyl group by using various methods. Synthesis of the oligosaccharide, which included the terminal structure of class III mucin, was achieved with single-column chromatographic purification. In addition, because of the symmetrical structure of 5, each fluorous synthetic intermediate could be analyzed much easier by NMR spectroscopy than in the case of the fluorous compounds connecting our previous fluorous tags.     

Fluorous-Assisted One-Pot Oligosaccharide Synthesis

A new method for oligosaccharide assembly that combines the advantages of one-pot synthesis and fluorous separation is described. After one-pot glycosylations are completed, a fluorous tag is introduced into the reaction mixture to selectively "catch" the desired oligosaccharide, which is rapidly separated from non-fluorous impurities by fluorous solid-phase extraction (F-SPE). Subsequent "release" of the fluo rous tag and F-SPE achieved the purification of the desired oligosaccharide without the use of time- and solvent-consuming silica gel chromatography. Linear and branched oligosaccharides have been synthesized with this approach in just a few hours (for the overall oligosaccharide assembly and purification process).     

Noncovalent Attachment of Nucleotides by Fluorous?Fluorous Interactions: Application to a Simple Purification Principle for Synthetic DNA Fragments

We report a highly efficient noncovalent immobilization of DNA fragments on surfaces by fluorous? fluorous interactions. The principle was applied to a simple and straightforward purification protocol for synthetic DNA. The method is completely compatible with standard solid‐phase synthesis of DNA.     

A practical fluorous benzylidene acetal protecting group for a quick synthesis of disaccharides

A new fluorous benzylidene acetal protecting group was regioselectively introduced into carbohydrates, deprotected under acidic conditions, and reused. Oligosaccharides were synthesized via regioselective conversion of the fluorous acetal group to the benzyl group by traditional reaction conditions. The fluorous compounds were easily separated from non-fluorous by-products by fluorous solid phase extraction.     

Rapid oligosaccharide synthesis on a fluorous support

The novel fluorous support Hfb (hexakisfluorous chain-type butanoyl) was easily prepared. The Hfb group was readily introduced into the anomeric hydroxyl group of a carbohydrate, and was recyclable after cleavage. The use of the Hfb group was applicable for the rapid oligosaccharide synthesis in which the synthetic intermediates could be purified using fluorous and normal organic solvents. Each synthetic intermediate could be monitored by TLC, NMR and mass spectrometry.     

Convertible Fluorous Sulfonate Linker for the Synthesis of Diverse Library Scaffolds

Aryl perfluorooctanesulfonates (fluorous sulfonate) have been developed as triflates and nonaflates alternatives for Pd‐catalyzed coupling reactions to form C‐C, C‐N, C‐S, C‐H, and C‐CN bonds. They also serve as phase‐tags for fluorous solid‐phase extraction (F‐SPE) to facilitate product purifications. Other synthetic techniques such as microwave reactions and multicomponent reactions are combined with the fluorous linker strategy to further increase synthetic efficiency. The utility of fluorous sulfonate linkers in the synthesis of biologically interested library scaffolds is summarized in this short review article.     

Separation of "light fluorous" reagents and catalysts by fluorous solid-phase extraction: synthesis and study of a family of triarylphosphines bearing linear and branched fluorous tags

Practical syntheses of new triarylphosphines bearing both linear and branched fluorous tags (Rf) are reported. The phosphines have one, two, or all three aryl rings bearing fluorous tags: (Ph)(3)(-)(n)()P(C(6)H(4)(CH(2))(m)()Rf)(n)(). Fluorous-organic partition coefficients have been measured and the retention properties of both the phosphines and the derived phosphine oxides on fluorous reverse phase silica have been studied. While applications relying on liquid-liquid extractive separations of these phosphines may be limited to those bearing three fluorous chains, the technique of solid phase extraction should be broadly applicable to phosphines, phosphine oxides, and derived metal complexes. A parallel platinum-catalyzed allylation of aldehydes with fluorous allyl stannanes illustrates the usefulness of the new fluorous ligands in small-scale synthesis.     

微波辅助组合合成的研究进展

微波辅助组合合成技术是近年来发展起来的一种新的制备化合物库的组合化学技术, 它不仅可以克服传统固相组合合成技术以及液相组合合成技术无法提高产物收率的不足, 而且利用该技术所制得的化合物库中对应的是高纯度的单一化合物, 采用高通量筛选技术可以快速直接地确定高活性结构, 极大地提高了新药开发的效率. 主要就近年来微波辅助组合合成技术的研究进展情况进行介绍, 内容包括固相组合合成、基于聚合物支载的催化剂的组合合成、液相组合合成、氟相组合合成以及组合平行合成等.     

Fluorous synthesis of sclerotigenin-type benzodiazepine-quinazolinones

A new synthetic protocol for sclerotigenin-type benzodiazepine-quinazolinone library scaffold is introduced. A fluorous benzyl protecting group is used for the synthesis of 4-benzodiazepine-2,5-dione intermediate and also as a phase tag for fluorous solid-phase extraction (F-SPE).     

Preparation of Perfluoroalkyl Substituted Saccharides and Their Distribution Ratio between Organic and Fluorous Sovlents

A "fluorous synthesis" approach is outlined in which organic molecules are rendered solublity in fluorocarbon solvents by attachment of a suitable fluorocanbon group. Fluorocarbon sovlents are immisicible in organic solutions, and fluorous molecules partition out of an organic phanse and into a fluorous phase in a standard liquid-liquid extraction. Simple yet substantive separations of organic reaction mixtures are achieved without resorting to chromatography. This methed has been used in many fields, but seldom in oligosacchride synthesis.     

Cover Picture: Journal of the Chinese Chemical Society 5/2011

Perflurooctanesulfonates (fluorous sulfonates) have been developed as triflates and nonaflates alternatives for Pd‐catalyzed coupling reactions to form C‐C, C‐N, C‐S, C‐H, and C‐CN bonds. They also serve as a phase‐tag for fluorous solid‐phase extraction (F‐SPE) to facilitate the product purification. The utility of fluorous sulfonate linkers in the synthesis of biologically interested library scaffolds is summarized in this short review article. This article entitled “Convertible Fluorous Sulfonate Linker for the Synthesis of Diverse Library Scaffolds“ was contributed by Prof. Wei Zhang who was invited as a Visiting Lecturer of the Chemistry Research Promotion Center, Taiwan, R.O.C. (November 23 ～ November 29, 2010). For full text, please see pp. 575～582 in this issue.     

Fluorous linker facilitated synthesis of teichoic acid fragments

The use of perfluorooctylpropylsulfonylethanol as a new phosphate protecting group and fluorous linker is evaluated in the stepwise solution phase synthesis of a number of biologically relevant (carbohydrate substituted) glycerol teichoic acid fragments. Teichoic acid fragments, up to the dodecamer level, were assembled by means of phosphoramidite chemistry, using a relatively small excess of the building blocks and a repetitive efficient purification procedure of the protected intermediates by fluorous solid phase extraction (F-SPE).     

Reverse fluorous solid-phase extraction: a new technique for rapid separation of fluorous compounds

Fluorous-tagged compounds can rapidly be separated from organic (non-tagged) compounds by the new separation technique of reverse fluorous solid-phase extraction (r-fspe). In a reversal of the roles of solid and liquid phases in standard fluorous spe, a mixture is charged to a polar solid phase (standard silica gel) and then eluted with a fluorous solvent or solvent mixture. The organic components of the mixture are retained, while the fluorous components pass. [structure: see text]     

Increasing fluorous partition coefficients by solvent tuning

Low partition coefficients of fluorous components have been a persistent problem in liquid-liquid separations using perfluoroalkanes as the fluorous phase. Solvent tuning of both the nonfluorous and the fluorous phase dramatically enhances the partitioning of light or polar fluorous molecules into the fluorous liquid phase, while minimally effecting partition coefficients of nonfluorous molecules. These findings suggest an expanded scope for liquid-based separations in fluorous biphasic catalysis, fluorous-tagged reagents, fluorous-supported oligomer synthesis, and related areas. [reaction: see text]     

Stereoselective conjugate radical additions: application of a fluorous oxazolidinone chiral auxiliary for efficient tin removal

[reaction: see text] A series of asymmetric free-radical-mediated intermolecular conjugate additions using a fluorous oxazolidinone chiral auxiliary has been completed. The fluorous auxiliary facilitated product isolation using fluorous solid phase extractions (FSPE), effectively removing excess organic and organometallic reagents. Parallel reactions carried out with a similar but nonfluorous norephedrine-derived oxazolidinone demonstrated the superior stereoselectivity and purification obtainable with the fluorous chiral auxiliary.