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Abstract

A series of prearranged glycosides 5, 17, 23, 28, 37, and 41, having a benzyl-protected 1-thiomannosyl donor linked through its positions 2, 3, 4, and 6 via succinate and malonate tethers, respectively, to positions 2, 3, and 6 of a benzyl glucopyranoside acceptor, were prepared by condensation of the respective mannosyl succinates and malonates with suitably protected benzyl glucopyranosides. The prearranged glycosides were intramolecularly coupled under various conditions to give the corresponding tethered (1 3 4)-linked disaccharides. The yields and anomer ratios of the products of these couplings were interpreted in terms of the thermodynamic stability of the resulting disaccharides. In the case of prearranged glycoside 17, having positions 3 of both the donor and the acceptor linked by a succinate tether, a strong dependence of the diastereoselectivity of the intramolecular glycosylation on the activation procedure was observed. All other cases did not show a significant dependence of the outcome of the anomeric configuration in intramolecular glycosylation on the activation procedure or the solvent.Prearranged glycosides tethered via position 4 of the respective mannosyl residues were prepared as follows. First, a suitably protected mannoside was needed to allow the introduction of the succinyl tether. Thus, phenyl 1-thiomannoside 25 was first prepared by opening of the benzylidene ring [46] of phenyl 2,3-di-O-benzyl-4,6-O-benzylidene-1thio-a-d-mannopyranoside (24) [51] (Scheme 3). Next, succinylation at position 4 afforded monosaccharide 26 (89%), which was again condensed with glucoside 3. The thus-obtained succinyl-tethered glycoside 27 (74%) was converted as described above to compound 28 (78%) and cyclized (see below, Table) to the tethered disaccharides 29. As previously observed for the tethered disaccharides 18, no assignment of the anomer configuration of saccharides 29a and 29b could be made by NMR spectroscopy (C(1) of the mannosyl residue at 100.4 (29a) and 100.8 ppm (28a); corresponding 1 J 175.0 (29a) and 173.7 Hz (29b)). Therefore, disaccharides 29 were each deacylated and benzoylated to give saccharides 30, which now showed characteristic C,H-coupling constants ( 1 J 174.1 Hz (30a) and 156.9 Hz (30b)). For comparison reasons, the Table (see below) also shows the already known results of the cyclization of compound 31, which established the formation of anomer mixtures of tethered disaccharides 32 and 33, respectively, depending on the reaction conditions [41].

Chemical Synthesis Elucidates the Key Antigenic Epitope of the Autism‐Related Bacterium Clostridium bolteae Capsular Octadecasaccharide

“…Unfortunately,p reactivation of thioglycoside 5 with Tf 2 Oa nd BSP in the presence of 2,4,6-tri-tert-butylpyrimidine (TTBP) at À60 8 8C and subsequent addition of the acceptor 6 [28] at À78 8 8Cl ed Then ext attempt at the synthesis of b-d-rhamnoside utilizes the Crichs b-mannosylation approach (thioglycoside/ BSP/Tf 2 Og lycosylation with conformationally-locked dmannose donor) and subsequent C6 deoxygenation. b-Mannoside 8 was synthesized by preactivating donor 9 [30] with Tf 2 Oand BSP in the presence of TTBP at À60 8 8Cand further glycosylation with the acceptor 10 [31] at À78 8 8Ci n8 2% yield and complete b-selectivity (Scheme 2A). The b-configuration of the newly formed glycosidic bond in 8 was clearly confirmed by the anomeric proton 1 J H1/C1 coupling of 156 Hz.…”

Intramolecular glycosylation

“…Valverde et al also investigated succinoyl tethers [ 54 ], but their studies were mainly focusing on phthaloyl and non-symmetrical linkers described below. Among other flexible linkers investigated are carbonate [ 57 ], as well as oxalic [ 57 ], malonic [ 53 , 57 – 58 ], and glutaric [ 59 ] dicarboxylic acids. However, like in the case of succinoyl linkers, higher flexibility led to more relaxed stereoselectivity.…”

“…However, like in the case of succinoyl linkers, higher flexibility led to more relaxed stereoselectivity. Further variations upon this method involved the modification of the macrocycle ring size, torsional rigidity of the spacer, position of the attachment to both donor and acceptor, relative configuration of hydroxy groups, and the length of the linker [ 58 , 60 – 72 ]. Among early examples, xylylene and phthalimido linker showed very high efficiency, and will be highlighted below.…”

“…It is a commonly accepted fact that the outcome of many glycosylations that fall under the general molecular clamp concept can be unpredictable. Therefore, practically every approach developed under this category was extensively studied and applied to a variety of sugar series and targets [ 58 , 73 – 74 ].…”

Templated Oligosaccharide Synthesis: Driving Forces and Mechanistic Aspects

“…Recently, we introduced a type of templated oligosaccharide synthesis, a method where glycosylations were performed using the general conventions of the “molecular clamp” concept. − Bisphenol A (BPA) was used as the template, and succinoyl, glutaryl, or phthaloyl linkers were used to tether glycosyl donors and acceptors together. The general outline of the templated synthesis is shown in Scheme .…”