Synthesis of the Non-Reducing Hexasaccharide Fragment of Saccharomicin B.
ABSTRACT: A synthesis of the nonreducing end hexasaccharide of saccharomicin B, ?-l-Eva-(1?4)-?-l-Eva-(1?4)-?-l-Dig-(1?4)-?-l-Eva-(1?4)-?-l-Dig-(1?4)-?-d-Fuc, has been developed. Selective glycosylations of l-digitoxose (l-Dig) using AgPF6/TTBP-mediated thioether activation and l-4-e pi-vancosamine (l-Eva) using Tf2O/DTBMP-mediated sulfoxide activation produced the hexasaccharide as a single diastereomer in very good yield. This hexasaccharide is properly functionalized to serve as a glycosyl donor for the total synthesis of saccharomicin B.
Project description:A concise synthesis of a branched trisaccharide, ?-l-Dig-(1 ? 3)-[?-l-Eva-(1 ? 4)]-?-d-Fuc, corresponding to saccharomicin B, has been developed via reagent-controlled ?-selective glycosylations. Starting from the d-fucose acceptor, l- epi-vancosamine was selectively installed using 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione/oxalyl bromide mediated dehydrative glycosylation. Following deprotection, l-digitoxose was installed using the AgPF6/TTBP thioether-activation method to produce the trisaccharide as a single ?-anomer. This highly functionalized trisaccharide can potentially serve as both a donor and an acceptor for the total synthesis of the antibiotic saccharomicin B.
Project description:A synthetic route has been developed for constructing the d-saccharosamine-l-rhamnose-d-fucose (Sac-Rha-Fuc) trisaccharide fragment present in the antibacterial natural product saccharomicin B. The Sac monosaccharide was synthesized through a modified nine step procedure starting from d-rhamnal in 23% overall yield. 1- O-TBS Sac donors were used to construct the ?-linked Sac-Rha disaccharide. This disaccharide was coupled to a Fuc acceptor under BSP/Tf2O conditions to afford a trisaccharide properly functionalized for elaboration to saccharomicin B.
Project description:An acid-promoted glycosylation and alkynol cycloisomerization sequence provided direct access to the 2-deoxytrisaccharide corresponding to the fucose-saccharosamine-digitoxose substructure of saccharomicin B. In the course of this work, the absolute stereochemistry of the repeating fucose-saccharosamine disaccharide of saccharomicins was also confirmed.
Project description:In explorations toward the total synthesis of the antitumor anthrapyran natural product kidamycin, the regioselective introduction of aminosugars angolosamine and vancosamine as C-arylglycosides has been accomplished onto hydroxylated anthrapyran aglycones. Specifically, the 9,11-dihydroxylated anthrapyran A undergoes sequential glycosylations with angolosamine synthon B and vancosamine synthon C to regio- and stereoselectively afford bis-C-glycoside D corresponding to the C-glycoside pattern of kidamycin.
Project description:Here, we report the synthesis of a sulfated, fully protected hexasaccharide as a glycosaminoglycan mimetic and the study of its interactions with different growth factors: midkine, basic fibroblast growth factor (FGF-2) and nerve growth factor (NGF). Following a fluorous-assisted approach, monosaccharide building blocks were successfully assembled and the target oligosaccharide was prepared in excellent yield. The use of more acid stable 4,6-O-silylidene protected glucosamine units was crucial for the efficiency of this strategy because harsh reaction conditions were needed in the glycosylations to avoid the formation of orthoester side products. Fluorescence polarization experiments demonstrated the strong interactions between the synthesized hexamer, and midkine and FGF-2. In addition, we have developed an alternative assay to analyse these molecular recognition events. The prepared oligosaccharide was non-covalently attached to a fluorous-functionalized microplate and the direct binding of the protein to the sugar-immobilized surface was measured, affording the corresponding KD,surf value.
Project description:A biotinylated heparosan hexasaccharide was synthesized using a one-pot multi-enzyme strategy, in situ activation and transfer of N-trifluoroacetylglucosamine (GlcNTFA) to a heparin backbone significantly improved the synthetic efficiency. The biotinylated hexasaccharide could serve as a flexible core to diversify its conversion into heparan sulfate isoforms with potential biological applications and therapeutics.
Project description:In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.
Project description:The synthesis of the hexasaccharide fragment of landomycin A is reported. Using p-toluenesulfonyl chloride mediated dehydrative glycosylation, we constructed the deoxy-sugar linkages in a stereoselective fashion without the need for temporary prosthetic groups to control selectivity. Through this approach, the hexasaccharide was obtained in 28 steps and 8.9% overall yield, which is an order of magnitude higher than that of previously reported approaches.
Project description:A synthetic strategy towards the potent cytostatic agent pluraflavin A has been developed. Formation of the enantioenriched anthrapyran core bearing a halogen atom enabled the introduction of the ??C-aryl glycoside by Stille cross-coupling and subsequent hydrogenation of the aryl glycal. Chemo- and stereoselective O-glycosylations of ??oliose and ??3-epi vancosamine residues afforded a fully glycosylated aromatic core. Attempts to install the dimethylamino group of the C-disaccharide suggest that introduction of an azide group by displacement and subsequent reduction may pave the way to the total synthesis of pluraflavin A.
Project description:The Gram-positive bacterium Streptococcus pneumoniae causes severe disease globally. Vaccines that prevent S. pneumoniae infections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate vaccines is the assembly of the trisaccharide ?-D-GalpNAc-(1?4)-[?-D-Glcp-(1?3)]-?-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations.