Glycosidation of Thioglycosides in the Presence of Bromine: Mechanism, Reactivity, and Stereoselectivity

Abstract

Elaborating on previous studies by Lemieux for highly reactive "armed" bromides, we discovered that β-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions.

Regenerative Glycosylation

“…33 A series of reactions between perbenzylated bromides with glycosyl acceptor 4 34 was performed as depicted in Table 1 (entries 1–3). First, a reaction of bromide 2 with acceptor 4 was performed in the presence of TMSOTf (0.08 equiv) as the activator and Ag 2 O (3.0 equiv) as the HBr scavenger.…”

Automated Chemical Synthesis of Oligosaccharides and Glycoconjugates

“…In an effort to obtain more complex oligosaccharide sequences, Takahashi adapted another instrument, Liquid Crystal on Silicon (L-COS) by Moritex, which was used to make a dimeric Le x (48) and its analogs. Using this instrument, Takahashi et al achieved automation of stirring, temperature control, and rate of reagent addition for each glycosylation and deprotection step shown in Fig.…”

“…Finally, the remaining 3′-OH of the resulting hexasaccharide intermediate was fucosylated by the addition of a donor (47) and NIS/TfOH. Resultantly, the desired heptasaccharide (48) was obtained in eight hours in 24% yield (average 79% yield per step). The automated synthesizer could be combined with Combi Flash automated column chromatograph, which was used for purification of the resulting oligosaccharides.…”

“…A five-port silicon microfluidic reactor was utilized for the synthesis of the homotetramer (52). For this purpose, a glycosyl phosphate donor (48) was first glycosidated with a fluorous linker (49) in the presence of TMSOTf [137]. To accomplish the glycosylation reaction in a microfluidic device, three separate solutions in dichloromethane were prepared: glycosyl acceptor, phosphate donor, and the activator (TMSOTf).…”

An unusual glycosylation product from a partially protected fucosyl donor under silver triflate activation conditions

“…The formation and characterisation of glycosyl bromides using in situ NMR analysis has previously been described by Demchenko and co-workers. 30 Formation of the glycosyl bromide was carried out in CDCl 3 in a standard NMR tube equipped with a septum and immersed in liquid nitrogen (−196°C). NMR analysis demonstrated that full conversion of the thioglycoside to the bromide 4 was complete within five minutes and that no disaccharide formation or anomerisation was observed even upon warming of the glycosyl bromide to room temperature (Fig.…”