Jimei Ma

Interfacing Glycosylated Carbon‐Nanotube‐Network Devices with Living Cells to Detect Dynamic Secretion of Biomolecules

A sense of cell-being: Single-walled carbon nanotubes (SWNTs) are functionalized with bioactive monosaccharides to enable their use as biosensors. The glycosylated nanotube network is biocompatible and can interface with living cells (see scheme) to electronically detect biomolecular release with high temporal resolution and high sensitivity.

Carbohydrate functionalized carbon nanotubes and their applications

Carbon nanotubes (CNTs) have attracted tremendous attention in biomedical applications due to their molecular size and unique properties. This tutorial review summarizes the strategies to functionalize CNTs with bioactive carbohydrates, which improve their solubility, biocompatibility and biofunctionalities while preserving their desired properties. In addition, studies on the usage of carbohydrate functionalized CNTs to detect bacteria, to bind to specific lectins, to deliver glycomimetic drug molecules into cells and to probe cellular activities as biosensors are reviewed. Improvement in biocompatibility and introduction of bio-functionalities by integration of carbohydrate with CNTs are paving the way to glyconanotechnology and may provide new tools for glycobiological studies.

Quick Access to Druglike Heterocycles: Facile Silver-Catalyzed One-Pot Multicomponent Synthesis of Aminoindolizines

A direct and efficient approach to 1-aminoindolizines through three-component one-pot reaction of heteroaryl aldehydes, secondary amines, and terminal alkynes catalyzed by AgBF(4) has been developed. Desired products were obtained in moderate to excellent yields. Similar aminoindolizines products were afforded from trimethylsilyl protected alkyne substrates as well. This methodology provides a rapid access to construct a diversity-oriented library of indolizines.

Sugar-based synthesis of Tamiflu and its inhibitory effects on cell secretion.

Tamiflu is currently the most effective drug for the treatment of influenza, but the insufficient supply and side-effects of this drug demand urgent solutions. We present a practical synthesis of Tamiflu by using novel synthetic routes, cheap reagents, and the abundantly available starting material D-glucal. The strategy features a Claisen rearrangement of hexose to obtain the cyclohexene backbone and introduction of diamino groups through tandem intramolecular aziridination and ring opening. In addition, this synthetic protocol allows late-stage functionalization for the flexible synthesis of Tamiflu analogues. By using the synthesized Tamiflu and its active metabolite (oseltamivir carboxylate), we investigated their influences on neuroendocrine PC12 cells in various aspects. It was discovered that oseltamivir carboxylate significantly inhibits the vesicular exocytosis (regulated secretion) of PC12 cells, and suggests a mechanism underlying the Tamiflu side-effects, in particular its possible adverse influences on neurotransmitter release in the central nervous system.

Stereoselective β‐C‐Glycosylation by a Palladium‐Catalyzed Decarboxylative Allylation: Formal Synthesis of Aspergillide A

The efficient stereoselective construction of glycosidic linkages is indubitably a principal focus in carbohydrate chemistry because it is necessary for the construction of natural glycoconjugates. Among the wide variety of glycosylation methods, the Ferrier reaction has received considerable attention as it provides convenient and direct access to 2,3unsaturated glycosides from glycals. However, the stringent requirement of glycosyl acceptors generally confines the reaction to specific nucleophiles with strong reactivity and the utilization of stoichiometric amounts of a Lewis acid is inevitable in some cases. In addition, the dominant anomeric effect leads to the stereoselective generation of a-glycosides for Ferrier-type O-glycosylation and therefore accents the rigidity of the reaction. On the other hand, most results from Ferrier C-glycosylation reactions remain mediocre as only moderate a-selectivity has been achieved. The pursuit of high b-selectivity is also extremely challenging and judging from the lack of substantial reports, the barriers surrounding this problem has not been solved. [Scheme 1, Eq. (1)]. Consequently, the combination of limitations surrounding the Ferrier reaction prompted researchers to develop other methods to synthesize 2,3-unsaturated glycosides in exclusive selectivity, especially b-selectivity. Recent demonstrations on the efficiency of palladiumcatalyzed coupling reactions have stimulated considerable interest in applying this strategy to carbohydrates, particularly for the synthesis of 2,3-unsaturated glycosides. One of the successful and prominent examples is the Heck-type glycosylation of glycals with arylboronic acids or aryl halides by transition-metal insertion and reductive elimination [Scheme 1, Eq. (2)]. The allylic feature of glycals also encouraged chemists to pursue the applicability of palladium-catalyzed allylic alkylation in glycosylation reactions [Scheme 1, Eq. (3)]. However, the formation of Pd p-allyl species in glycal systems has long been recognized as tedious and difficult. To overcome this challenge, the more activated pyranone system was generated and additional activators were employed. Following the removal of this hurdle, great strides were made in decarboxylative allylation (DcA). 10] In particular, intramolecular decarboxylative allylation has developed into an area of great potential among the transition-metal-catalyzed decarboxylative coupling reactions which have drawn considerable attention in the area of C C bond formation. The Tunge, Trost, and Stoltz groups, for instance, have reported a series of catalytic decarboxylative allylation and benzylation reactions. Inspired by these reports, we envisioned that the palladiumcatalyzed decarboxylation of the C-3 ester of glycal would be helpful in the formation of a Pd p-allyl intermediate which might accomplish the desired C-glycosylation with high stereoselectivity [Scheme 1, Eq. (4)]. In a continuation of our work on developing efficient glycosylation methods, we report herein on a palladium-catalyzed stereoand regioselective C-glycosylation by means of intramolecular decarboxylative coupling. In initial studies, the decarboxylative coupling reaction of compound 1a was carried out in the presence of a catalytic amount of [Pd(PPh3)4] in DMF at 80 8C for 12 h. To our delight, the regiospecific coupling product 2a was obtained in 50% yield with a b/a ratio of 6:1 (Table 1, entry 1). To improve the yield and selectivity, various Pd catalysts were screened with the 1,2-bis(diphenylphosphino)ethane (DPPE) ligand in DMF (Table 1, entries 2–4). We found that the reaction catalyzed by Pd(OAc)2 gave better yield and Scheme 1. Various types of glycosylation.

A Short and Highly Efficient Synthesis of l-Ristosamine and l-epi-Daunosamine Glycosides

A highly efficient synthesis of L-ristosamine and L-epi-daunosamine glycosides via BF(3)·OEt(2) promoted tandem hydroamination/glycosylation of 3,4-di-O-acetyl-6-deoxy-L-glucal and L-galactal has been developed. The new method proceeds in a completely stereocontrolled manner within a short reaction time. Preparation of a library of L-ristosamine and L-epi-daunosamine glycosides with potential biochemical applications, by varying each component, exemplified the generality of the reaction.

(S)-Camphorsulfonic acid catalyzed highly stereoselective synthesis of pseudoglycosides.

A mild and efficient synthesis of pseudoglycosides has been developed using metal free (S)-camphorsulfonic acid. (S)-CSA acts as an excellent catalyst for conversion of 2,4,6-tri-O-acetyl-D-glucal to 2,3-unsaturated O-glycosides. A wide range of biologically active natural products, alcohols and thiols could be coupled with glucal to give the desired pseudoglycosides in good to excellent yields with exclusive alpha-stereoselectivity.

Facile access to cis-2,6-disubstituted tetrahydropyrans by palladium-catalyzed decarboxylative allylation : total syntheses of (±)-centrolobine and (+)-decytospolides A and B

cis-2,6-Tetrahydropyran is an important structural skeleton of bioactive natural products. A facile synthesis of cis-2,6-disubstituted-3,6-dihydropyrans as cis-2,6-tetrahydropyran precursors has been achieved in high regio- and stereoselectivity with high yields. This reaction involves a palladium-catalyzed decarboxylative allylation of various 3,4-dihydro-2H-pyran substrates. Extending this reaction to 1,2-unsaturated carbohydrates allowed the achievement of challenging β-C-glycosylation. Based on this methodology, the total syntheses of (±)-centrolobine and (+)-decytospolides A and B were achieved in concise steps and overall high yields.

Total Synthesis of Sialic Acid by a Sequential Rhodium‐Catalyzed Aziridination and Barbier Allylation of D‐Glycal

The synthesisof 2-amino-2-deoxypyranoside residues is chal-lenging in two ways: the selective functionaliza-tion of the nitrogen moiety at the C2-position,and the formation of the glycosidic bond withappropriate glycosyl acceptors. Nowadays, gly-cals are often employed as versatile startingmaterials for such syntheses. Numerous methodshave been developed for the direct introductionof a nitrogen substituent at the C2-position ofglycals. These approaches involve inter- or intra-molecular addition of a nitrogen atom to a glycalscaffold, which generates an aziridine intermedi-ate, followed by ring opening with a nucleophile.These methods have been developed as generalpathways to generate 2-amino sugars.

Green glycosylation promoted by reusable biomass carbonaceous solid acid: an easy access to β-stereoselective terpene galactosides

An efficient green protocol has been developed for the atom economic glycosylation of unprotected, unactivated glycosyl donors and glycosylation of glycosyl trichloroacetimidates with the aid of reusable eco-friendly biomass carbonaceous solid acid as catalyst.