Revisiting the armed-disarmed concept: the importance of anomeric configuration in the activation of S-benzoxazolyl glycosides

The unexpectedly high reactivity of a (2-benzoxazolyl) per-O-benzoyl-beta-D-thioglucoside and related donors in reactions promoted by copper(II) trifluoromethanesulfonate is revealed, by comparison with the unreactive alpha-anomer, to be the result of neighboring group participation. Revision of the armed-disarmed concept for glycosyl donors is not required.     

How the arming participating moieties can broaden the scope of chemoselective oligosaccharide synthesis by allowing the inverse armed-disarmed approach

A new method for stereocontrolled glycosylation and chemoselective oligosaccharide synthesis has been developed. It has been determined that complete 1,2-trans selectivity can be achieved with the use of a 2-O-picolyl moiety, a novel neighboring group that is capable of efficient participation via a six-membered intermediate. The application of the picolyl concept to glycosidations of thioimidoyl, thioglycosyl, and trichloroacetimidoyl glycosyl donors is demonstrated. The picolyl moiety also retains the glycosyl donor in the armed state, as opposed to conventional acyl participating moieties. We name this new approach the "inverse armed-disarmed" strategy, because it allows for the chemoselective introduction of a 1,2-trans glycosidic linkage prior to other linkages. In the context of the oligosaccharide synthesis, the strategy provides trans-trans and trans-cis patterned oligosaccharides as opposed to classic Fraser-Reid's armed-disarmed approach leading to cis-trans and cis-cis linkages.     

Application of the superarmed glycosyl donor to chemoselective oligosaccharide synthesis

Recently, we discovered a novel method for "superarming" glycosyl donors. Herein, this concept has been exemplified in one-pot oligosaccharide syntheses, whereby the superarmed glycosyl donor was chemoselectively activated over traditional "armed" and disarmed glycosyl acceptors. Direct side-by-side comparison of the reactivities of the classic armed and superarmed glycosyl donors further validates the credibility of the novel concept.     

S-thiazolinyl (STaz) glycosides as versatile building blocks for convergent selective, chemoselective, and orthogonal oligosaccharide synthesis

In the aim of developing new procedures for efficient oligosaccharide assembly, a range of S-thiazolinyl (STaz) glycosides have been synthesized. These novel derivatives were evaluated against a variety of reaction conditions and were shown to be capable of being chemoselectively activated in the armed-disarmed fashion. Moreover, the S-thiazolinyl moiety exhibited a remarkable propensity for selective activation over other common leaving groups. Conversely, a variety of leaving groups could be selectively activated over the STaz moiety, which, in turn, allowed STaz/S-ethyl and STaz/S-phenyl orthogonal approaches. To demonstrate versatility of novel STaz derivatives, a number of oligosaccharide targets have been synthesized in a convergent selective, orthogonal, and chemoselective fashion.     

Selective acetolysis of 6-deoxy-sugar oligosaccharide building blocks governed by the armed-disarmed effect

The effect of the arming-disarming protection in the acetolysis of 6-deoxy-sugar oligosaccharides has been for the first time systematically investigated. Starting from the newly synthesized methyl glycosides, the acetolysis conditions employed here afforded 1-O-Ac oligosaccharides selectively without cleavage of the interglycosidic bonds, if a suitable protecting group pattern was used. Actually, the behavior of armed-disarmed, armed-armed, and disarmed-disarmed 6-deoxy-sugar disaccharides in acetolysis reactions was investigated: the results fit well with the prediction made on the basis of the armed-disarmed effect.     

Revisiting the Zintl-Klemm concept: alkali metal trielides

To enhance understanding of the Zintl-Klemm concept, which is useful for characterizing chemical bonding in semimetallic and semiconducting valence compounds, and to more effectively rationalize the structures of Zintl phases, we present a partitioning scheme of the total energy calculated on numerous possible structures of the alkali metal trielides, LiAl, LiTl, NaTl, and KTl, using first-principles quantum mechanical calculations. This assessment of the total energy considers the relative effects of covalent, ionic, and metallic interactions, all of which are important to understand the complete structural behavior of Zintl phases. In particular, valence electron transfer and anisotropic covalent interactions, explicitly employed by the Zintl-Klemm concept, are often in competition with isotropic, volume-dependent metallic and ionic interaction terms. Furthermore, factors including relativistic effects, electronegativity differences, and atomic size ratios between the alkali metal and triel atoms can affect the competition by enhancing or weakening one of the three energetic contributors and thus cause structural variations. This partitioning of the total energy, coupled with analysis of the electronic density of states curves, correctly predicts and rationalizes the structures of LiAl, LiTl, NaTl, and KTl, as well as identifies a pressure-induced phase transition in KTl from its structure, based on [Tl(6)](6-) distorted octahedra, to the double diamond NaTl-type.     

A novel strategy for oligosaccharide synthesis via temporarily deactivated S-thiazolyl glycosides as glycosyl acceptors

A new glycosylation strategy that allows chemoselective activation of the S-thiazolyl (STaz) moiety of a glycosyl donor over the temporarily deactivated glycosyl acceptor, bearing the same anomeric group, has been developed. This deactivation is achieved by engaging of the STaz moiety of the glycosyl acceptor into a stable palladium(II) complex. Therefore, obtained disaccharides are then released from the complex by simple ligand exchange. [reaction: see text]     

Simplifying oligosaccharide synthesis: efficient synthesis of lactosamine and siaylated lactosamine oligosaccharide donors

A practical sequence is described for converting d-glucosamine into peracetylated Gal(beta-1,4)GlcNTroc(beta1-S)Ph and Neu5Ac(alpha-2,3)Gal(beta-1,4)GlcNTroc(beta1-S)Ph building blocks using a synthetic strategy based on chemoenzymatic oligosaccharide synthesis. The known trichloroethoxycarbonyl, N-Troc, protecting group was selected as a suitable protecting group for both enzymatic and chemical reaction conditions. These oligosaccharide building blocks proved effective donors for the beta-selective glycosylation of the unreactive OH-3 of a polymeric PEG-bound acceptor and for the axial OH-2 of a mannose acceptor in good yields. The resulting complex oligosaccharides are useful for vaccine and pharmaceutical applications.     

Vinyl glycosides in oligosaccharide synthesis (part 5): A latent-active glycosylation strategy for the preparation of branched trisaccharide libraries

For the first time, an efficient strategy is described for the preparation of orthogonally protected branched and linear saccharide libraries which can be further functionalised. A small number of key building blocks can be converted into a wide range of glycosyl donors and acceptors.     

Fluorous thiols in oligosaccharide synthesis

A new, almost odorless fluorous thiol is synthesized, which is utilized to prepare highly fluorinated thioglycosyl donors. These thioglycosides showed excellent reactivities in glycosylation reactions. The fluorous chain, stable under esterification, etherification, deacetylation, and glycosylation conditions, allowed facile purification of the thioglycosides by solid-phase extraction through fluorous silica gel. The fluorous thiol was readily recycled.     

Recent developments in oligosaccharide synthesis: tactics,solid-phase synthesis and library synthesis

Oligosaccharides, commonly found on the cell surfaces, are deeply involved in a variety of important biological functions, yet demanding difficulties synthesizing such structures limit the investigation of their functions. Technologies to chemically synthesize these oligosaccharides have dramatically advanced during the last two decades mainly due to the introduction of good anomeric leaving groups. In addition, tactical analyses have been addressed to enhance the overall efficiency of oligosaccharide synthesis. Based on the advancement of solution-phase chemistry, solid-phase technologies are being investigated in connection with the current trend of combinatorial chemistry and high throughput screening. This review summarizes the necessary solution-phase methodologies, the status of solid-phase synthesis of oligosaccharides, and combinatorial synthesis of oligosaccharide libraries.     

Anomeric reactivity-based one-pot oligosaccharide synthesis: a rapid route to oligosaccharide libraries

The assembly of an oligosaccharide library has been achieved in a practical and efficient manner employing a' one-pot sequential approach. With the help of the anomeric reactivity values of thioglycosides, using a thioglycoside (mono- or disaccharide) with one free hydroxyl group as acceptor and donor coupled with another fully protected thioglycoside, a di- or trisaccharide is selectively formed without self-condensation and subsequently reacted in situ with an anomerically inactive glycoside (mono- or disaccharide) to form a tri- or tetrasaccharide in high overall yield. The approach enables the rapid assembly of 33 linear or branched fully protected oligosaccharides using designed building blocks. These fully protected oligosaccharides have been partially or completely deprotected to create 29 more structures to further increase the diversity of the library.     

Recyclable benzyl-type fluorous tags: Preparation and application in oligosaccharide synthesis

We herein described the design, synthesis and application of two recyclable benzyl-type fluorous tags with double fluorous chains. The benzyl-type fluorous tags were prepared in 3 steps from a commercially available fluorous alcohol. The glycosylation of the benzyl-type tags with imidate donors proceeded smoothly to provide the corresponding fluorous-tagged carbohydrates in good to excellent yields, which were readily purified by fluorous solid-phase extraction(FSPE). Efficient removal of the tags from tagtethered carbohydrates were conducted under the common catalytic hydrogenation condition and the initial benzyl-type fluorous tags could be regenerated [5_TD$IF]via a 2-step simple procedure in 69%–93% yields.The utility of the new benzyl-fluorous tag was demonstrated [7_TD$IF]via the FSPE-assisted synthesis of oligosaccharides Gb3.     

Tag-reporter and resin capture--release strategy in oligosaccharide synthesis

Low molecular weight poly(ethylene glycol) (LWPEG) has been found to be useful as a "tag" in oligosaccharide synthesis due to its high polarity. Real-time reaction monitoring was achieved by use of MALDI-TOF MS in the glycosylation reactions and color tests in the deprotection of the chloroacetyl group. Further, a cysteine-supported insoluble resin enables the purification of the chloroacetyl-bound compounds on soluble PEG.