Lewis Acids as α-Directing Additives in Glycosylations by Using 2,3-O-Carbonate-Protected Glucose and Galactose Thioglycoside Donors Based on Preactivation Protocol

Abstract

Catalytic or stoichiometric amounts of Lewis acids were found to be very effective α-directing additives in the stereoselective glycosylations of diverse 2,3-O-carbonateprotected glucose and galactose thioglycoside donors by preactivation protocol. The poor stereoselectivities of 4,6-di-Oacetyl-2,3-O-carbonate protected thioglycoside donors in glycosyl coupling reactions were greatly improved, and excellent αstereoselectivities were achieved by the addition of 0.2 equiv of BF 3 •OEt 2 . On the other hand, the β-selectivities of 4,6-di-Obenzyl-2,3-O-carbonate-protected thioglucoside donor toward glycosylations were reversed completely to the α-selectivities by the use of 1 equiv of SnCl 4 , making the stereoselectivity controllable. Furthermore, the poor stereoselectivities of 4,6-di-O-benzyl-2,3-O-carbonate-protected thiogalactoside donor in glycosylations were also improved by using SnCl 4 as additive.

Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry

“…25d Ye and co-workers studied 2,3- O -carbonyl protected glucose and galactose donors for pre-activation-based glycosylation. 84 These reactions were generally β-stereoselective, but Lewis acid additives were found to favor α-stereoselectivity ( vide infra ). A beneficial effect of a bulky 4,6- O -di- tert -butylsilylene (DTBS) protecting group 85 on α-selective galactosylation and galactosamination was recently applied to the synthesis of a series of human ABO histo-blood group type 2 antigens by Kiso and co-workers.…”

Pre‐Activation‐Based Stereoselective Glycosylations

“…The isomerization was believed to go through an endocyclic cleavage pathway . Recognizing this, the Ye group investigated Lewis acid as useful additives to mediate α‐selective glycoside formation . When the 2,3‐ O ‐carbonate‐protected donors reacted with acceptors under the pre‐activation condition without an additive, only slight α selectivities were obtained (Scheme a).…”

1,2-cis Alkyl glycosides: straightforward glycosylation from unprotected 1-thioglycosyl donors

“…6 Generally, 1,2-trans-alkyl glycosidation can be reliably achieved via neighboring-group participation of a C-2 acyl group on a glycosyl donor, while stereochemical control for 1,2-cis-alkyl glycosidation can be challenging. 7 The conventional Fischer glycosidation reaction, a straightforward way to afford short-chain, uncomplicated, thermodynamically favored 1,2-cis-alkyl glycosides, has been improved by using various acid catalysts, [8][9][10] microwave irradiation, 11 ultrasonication, 12 and ionic liquids. 13 Since free sugars have limited solubility in longer chain alcohols (acceptors), harsh conditions (e.g., high temperature, microwave, ultrasonication) are often required to push the reaction, which results in decomposition of the products, 8 formation of various side products, time-consuming separation processes, and low yields and poor stereoselectivities.…”

“…[α] 20 D +139.1 (c 1.00, CHCl 3 ). 1 H NMR (500 MHz, CDCl 3 ): δ 5.45 (1H, dd, J = 3.4, 1.3 Hz, H-4), 5.36-5.32 (1H, m, H-3), 5.12 (1H, m, H-2), 5.10 (1H, d, J = 3.4 Hz, H-1), 4.21 (1H, m, H-5), 4.10 (2H, m, H-6 a , H-6 b ),3.73 (1H, dt, J = 9.9, 6.1 Hz, one of OCH 2 CH 2 CH 2 CH 2 -CuCH 3.45 (1H, dt, J = 9.9, 6.3 Hz, the other one of OCH 2 CH 2 CH 2 CH 2 -CuCH), 2.23 (2H, tdd, J = 6.9, 2.7, 0 7. Hz, OCH 2 CH 2 CH 2 CH 2 -CuCH), 2.14, 2.07, 2.04, 1.98 (12H, 4 s, 4 × COCH 3 ), 1.95 (1H, t, J = 2.6 Hz, OCH 2 CH 2 CH 2 CH 2 -CuCH), CH 2 CH 2 CH 2 -CuCH).…”