Direct and stereoselective synthesis of β-d-mannosides using 4,6-O-benzylidene-protected mannosyl diethyl phosphite as a donor

Abstract

Leave this area blank for abstract info. Abstract-A direct and practical method for the construction of β-mannosidic linkages is described. While β-selectivities in the TMSOTfpromoted glycosidation of 2,3,4,6-tetra-O-benzyl-D-mannosyl diethyl phosphite are found to be highly dependent on the reactivity of acceptor alcohols, 2,3-di-O-benzyl-4,6-O-benzylidene-D-mannosyl diethyl phosphite reacts with a wide range of acceptor alcohols in the presence of TMSOTf in CH 2 Cl 2 at -45 °C to give β-mannosides in high yields with good to high β-selectivities.

Rate‐Dependent Inverse‐Addition β‐Selective Mannosylation and Contiguous Sequential Glycosylation Involving β‐Mannosidic Bond Formation

“…It should be noted that the loss of β‐selectivity in the absence of triflate‐based promoters has also been reported by other studies 16e. 17k, 34 A possible explanation is that when TMSOTf was used, the counter anion of the mannosyl oxocarbenium ion was the triflate anion and thus the two ions quickly coupled to generate the covalent α‐mannosyl triflate. This α‐mannosyl triflate would follow an S N 2‐like pathway and produce the β‐mannoside.…”

“…However, the improvement of β‐selectivity was less pronounced in the glycosylations of diisopropylidene acetal protected galactopyranosyl acceptor 8 (entries 4–6). A search in literature revealed that the β‐mannosylations of the galactopyranosyl acceptor 8 often result in modest β‐selectivities to other glycosyl acceptors 17k. 31 This peculiar result may be due to a mismatched interaction between the mannosyl donor 6 and galactopyranosyl acceptor 8 in the transition state leading to β‐anomer formation 32.…”

“…Another possible explanation is the erosion in selectivity of β‐mannosylation when a highly reactive acceptor is employed 17d. j, k To clarify the exact cause, methyl 2,3,4‐tri‐ O benzyl glucopyranoside 9 , which bears a C‐6 hydroxyl function, was prepared and used as a reactive acceptor for glycosylation with mannosyl donor 6 . Remarkably, the glycosylation produced the desired disaccharide 12α , 12β with excellent β‐selectivity (entry 7).…”

“…For the β‐anomer of disaccharide 10β : R f =0.30 (EtOAc/hexane 1:3); 1 H NMR (300 MHz, CDCl 3 ): δ =7.50 (dt, J =8.0, 4.3 Hz, 4 H; Ar H ), 7.46–7.23 (m, 26 H; Ar H ), 5.55 (s, 1 H; benzylidene‐C H ), 5.08 (d, J =10.7 Hz, 1 H; PhC H 2 ), 4.87–4.73 (m, 5 H), 4.72–4.57 (m, 5 H), 4.39 (s, 1 H), 4.31 (d, J =12.1 Hz, 1 H), 4.15–4.03 (m, 2 H), 3.96–3.84 (m, 2 H), 3.67 (d, J =2.9 Hz, 1 H), 3.62 (dd, J =8.0, 4.8 Hz, 1 H), 3.58–3.52 (m, 1 H), 3.49 (dd, J =11.1, 2.7 Hz, 1 H), 3.43 (s, 3 H; OC H 3 ), 3.36 (dd, J =10.0, 2.9 Hz, 2 H), 3.08–3.01 ppm (m, 1 H); 13 C NMR (75 MHz, CDCl 3 ): δ =139.8, 139.0, 138.9, 138.7, 138.0, 137.9, 129.2, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.2, 128.1, 127.96, 127.91, 127.7, 127.6, 126.5, 101.9 (benzylidene‐ C H), 101.7 (C‐1′), 98.8 (C‐1), 80.6, 79.3, 79.1, 78.6, 78.0, 77.6, 75.7, 75.4, 74.0, 73.9, 72.9, 70.0, 68.9, 68.7, 67.6, 55.7 ppm (O C H 3 ) 17c. g, k…”

Design, Synthesis, and Insecticidal Activities of Novel Pyranoside Derivatives Targeting at Potential Second Calcium Channel IP3 Receptor

“…[26] To our delight, the desired product was isolated in 10% yield (Entry 3). [30] Product 5f should be also stored in a freezer under nitrogen. To our disappointment, elevating the reaction temperature merely led to some side rections (Entry 4).…”