On the Stereochemistry of Tethered Intermediates inp-Methoxybenzyl-Assisted β-Mannosylation

Abstract

We have previously developed a novel method for the stereocontrolled synthesis of β‐manno‐glycoside. Starting from 2‐O‐PMB (p‐methoxybenzyl)‐protected mannosyl donor 1, conversion into the mixed acetal 3 under oxidative conditions followed by the activation of the anomeric position affords β‐manno‐glycoside as a single stereoisomer. Although the utility of this method has been further demonstrated in the synthesis of the core structure of Asn‐linked glycan chains, there remained uncertainty with respect to the stereochemistry of the mixed acetal. In order to make a stereochemical assignment of this intermediate, diastereomeric acetals 14a, 15a and 14b, 15b were prepared from 9 + 10/7 and 11 + 12/13, respectively. Investigations by means of NMR and a computational approach using DADAS 90 for quantifying steric hindrance, resulted in the conclusion that 14a/15a derived from 2‐O‐PMB‐protected 9 has an (S) configuration and 14b/15b derived from 2‐O‐unprotected 11 has an (R) configuration. Based on the characteristic 1H‐NMR patterns inherent to the (S) isomers, 4,6‐O‐benzylidene‐protected 30–35, derived from thiomannosides 5, 23, 24, 26, 27, were also revealed to have the (S) configuration.

Synthetic Studies on Glycosphingolipids from Protostomia Phyla: Synthesis of Amphoteric Glycolipid Analogues from the Porcine Nematode, Ascaris suum.

“…A stereochemical assignment of this intermediate was mentioned by Ito and co-workers. 27) Subsequent IAD was effected by methyl trifluoromethanesulfonate (MeOTf) and 2,6-di-tert-butyl-4-methylpyridine (DTBMP) in dichloromethane to afford the desired b-mannoside 12 in 35% yield and the a-mannoside was not detected. The anomeric hydrogen atom of the mannose unit appeared as a signal at d 4.41 (s, H-1Ј) by the 1 H-NMR spectrum.…”

“…Octyl 4, (11) were prepared by literature method. [25][26][27] Octyl 2,3,6-Tri-O-benzyl-b b-D-glucopyranoside (4) To a solution of 3 (1.82 g, 3 mmol) and NaBH 3 CN (1.64 g, 24 mmol) in dry tetrahydrofuran (THF) (10 ml) was added 3A MS, and the mixture was stirred for 2 h at room temperature, then cooled to 0°C. HCl-Et 2 O was added until the solution was acidic (pH paper, gas evolution).…”

My Stroll in the Backyard of Carbohydrate Chemistry

“…(12,40). Stereochemical and mechanistic insights of this reaction were also attained by modeling and with NMR spectroscopy (41,42). More recently, a 2-O-NAP (NAP: naphthylmethyl)-protected donor was shown to be more efficient, giving a variety of 1,2-cis-glycosides (β-Man, α-Glc, β-Araf ...) in a highly selective manner (43).…”

Intramolecular aglycon delivery

“…[17][18][19][20][21][22][23][24][25][26][27] Tethering proceeded very efficiently using a slight excess of either donor or acceptor (typically 1.1-1.4 equiv relative to the other component) to give mixed acetals, which were either purified by size-exclusion chromatography or used crude in the next step. Activation with MeOTf, DTBMP, 4 Å in DCE or DCM gave the b-mannosides exclusively.…”

“…Ito and Ogawa showed that in a reverse tethering approach, where the PMB ether is attached to the aglycon (i.e., at the position to be glycosylated) and tethered to a glycosyl fluoride with free OH-2, the mixed acetal can be formed, but as a different diastereomer (i.e., opposite configuration at the new centre) or a mixture of diastereomers (Scheme 9). 21 The origin of the stereoselectivity is obscure, but it seems that the reaction operates under kinetic control. NOE measurements and computational studies were used to deduce the configuration at the newly formed stereogenic centre (from the forward tethering approach shown in Tables 4 and 5), which was assigned as S.…”