Diastereoselective desymmetric 1,2-cis-glycosylation of meso-diols via chirality transfer from a glycosyl donor

Chemical desymmetrization reactions of meso-diols are highly effective for the precise and efficient synthesis of chiral molecules. However, even though enzyme-catalyzed desymmetric glycosylations are frequently found in nature, there is no method for highly diastereoselective desymmetric chemical glycosylation of meso-diols. Herein, we report a highly diastereoselective desymmetric 1,2-cis-glycosylation of meso-diols found in myo-inositol 1,3,5-orthoesters using a boronic acid catalyst based on predictions of regioselectivity by density functional theory (DFT) calculations. The enantiotopic hydroxyl groups of the meso-diols are clearly differentiated by the stereochemistry at the C2 position of the glycosyl donor with excellent regioselectivities. In addition, the present method is successfully applied to the synthesis of core structures of phosphatidylinositolmannosides (PIMs) and glycosylphosphatidylinositol (GPI) anchors, and common β-mannoside structures of the LLBM-782 series of antibiotics.

ESI-TOF Mass spectra were measured on a Waters LCT premier XE. Melting points were determined on a micro hot-stage (Yanako MP-S3) and were uncorrected. Optical rotations were measured on a JASCO P-2200 polarimeter. Silica gel TLC, column chromatography, and reverse-phase column chromatography were performed using Merck TLC 60F-254, Silica Gel 60 N (spherical, neutral, 63-210 μm or 40-50 m) (Kanto Chemical Co., Inc.). Air-and/or moisture-sensitive reactions were carried out under an argon atmosphere using oven-dried glassware. 1,2-Anhydro donor 36 was prepared as described by Wei et al 6 .
The glycosylation sites of (1,6)-D-glucosides were determined as described below.

Determination of glycosylation site of 9
Comparison of NMR data of acetylated -D-glucosides 64 and 65 Supplementary  Hz) 5  Synthesis of -D-glucoside 23 from 20 synthesized by our desymmetric glycosylation of meso-diol 13.

Determination of glycosylation site of 20
Comparison of NMR data of -D-glucosides 23 Supplementary

Determination of glycosylation site of 26
Comparison of
After the reaction mixture was stirred for 18 h at room temperature, the reaction was quenched by addition of H2O (20 mL). The resultant mixture was extracted with EtOAc (40 mL×3), and then the extracts were washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated in vacuo.

inositol-1,3,5-orthoformate (92)
To a solution of 88 (13.0 mg, 15.8 mol) in MeOH (630 L) was added NaOMe ( To a solution of crude 90 (10.1 mg) in CH2Cl2 (1.4 mL) was added Dess-Martin periodinane (17.8 mg, 42.0 mol) at room temperature. After the reaction mixture was stirred for 30 min at room temperature, the reaction mixture was filtered through celite pad, and to the filtrate was added sat.
The aqueous layer was extracted with CHCl3 (1 mL×3