Reaction #162021

ord-f488dd4163d54d7e958e7cbf9d3fb91c

Reaction equation

O=C(OC[C@H]1O[C@H](O[C@@H]2[C@H](OC(=O)c3ccccc3)[C@@H](OCc3ccccc3)O[C@H](COC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H](O)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
alcohol
O=C(OC[C@H]1O[C@H](O[C@@H]2[C@H](OC(=O)c3ccccc3)[C@@H](OCc3ccccc3)O[C@H](COC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H](O)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Benzyl 2,4,6-tri-O-benzoyl-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O-benzoyl-α-D-mannopyranoside
N=C(O[C@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)C(Cl)(Cl)Cl
2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate
C[Si](C)(C)OS(=O)(=O)C(F)(F)F
TMSOTf
c1ccncc1
Pyridine
O=C(Cl)c1ccccc1
benzoyl chloride
→
O=C(OC[C@H]1O[C@H](O[C@@H]2[C@H](OC(=O)c3ccccc3)[C@@H](O[C@@H]3[C@H](OC(=O)c4ccccc4)[C@@H](OCc4ccccc4)O[C@H](COC(=O)c4ccccc4)[C@H]3OC(=O)c3ccccc3)O[C@H](COC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
trisaccharide
Yield 60.0%
O=C(OC[C@H]1O[C@H](O[C@@H]2[C@H](OC(=O)c3ccccc3)[C@@H](O[C@@H]3[C@H](OC(=O)c4ccccc4)[C@@H](OCc4ccccc4)O[C@H](COC(=O)c4ccccc4)[C@H]3OC(=O)c3ccccc3)O[C@H](COC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Benzyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O-benzoyl-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O-benzoyl-α-D-mannopyranoside
Yield 60.0%

Reactants

O=C(OC[C@H]1O[C@H](O[C@@H]2[C@H](OC(=O)c3ccccc3)[C@@H](OCc3ccccc3)O[C@H](COC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H](O)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
alcohol
O=C(OC[C@H]1O[C@H](O[C@@H]2[C@H](OC(=O)c3ccccc3)[C@@H](OCc3ccccc3)O[C@H](COC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H](O)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Benzyl 2,4,6-tri-O-benzoyl-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O-benzoyl-α-D-mannopyranoside
N=C(O[C@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)C(Cl)(Cl)Cl
2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate
C[Si](C)(C)OS(=O)(=O)C(F)(F)F
TMSOTf
c1ccncc1
Pyridine
O=C(Cl)c1ccccc1
benzoyl chloride

Reagents

None

Solvents

CCN(CC)CC
Et3N
ClCCl
DCM
ClCCl
DCM

Conditions

Temperature
0°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.STIRRINGThe mixture was stirred at room temperature o/n and
  2. 2
    Otherevaporated onto silica gel
  3. 3
    OtherPurification
  4. 4
    Washby column chromatography (silica 2.5×17 cm, gradient elution with hexane-EtOAc 210:30, 200:50, 180:60, 160:80 and 150:100)

Procedure

A solution of the alcohol 50 (424 mg, 0.401 mmol) and 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (357 mg, 0.481 mmol, 1.2 eq) in anhydrous DCM (7.5 mL) was stirred with powdered molecular sieves 3 Å (50 mg) at 0° C. for 1 h. A solution of TMSOTf (15 μL, 0.0802 mmol, 0.2 eq) in DCM (0.5 mL) was added dropwise via a syringe. The mixture was stirred at 0° C. for 2 h and TLC indicated complete conversion. Et3N (100 μL) was added. Pyridine (65 μL, 0.802 mmol) and benzoyl chloride (47 μL, 0.401 mmol) were added. The mixture was stirred at room temperature o/n and evaporated onto silica gel. Purification by column chromatography (silica 2.5×17 cm, gradient elution with hexane-EtOAc 210:30, 200:50, 180:60, 160:80 and 150:100) gave the trisaccharide 51 as a colourless gum (392 mg, 60%). 1H NMR (CDCl3, 400 MHz) δ 8.19-7.89 (m, 16H, Ph), 7.68-7.63 (m, 4H, Ph), 7.61-7.15 (m, 35H, Ph), 6.00 (dd or t, 1H, JH3-H4=10.7, JH4-H5=9.8, H4), 5.98 (dd or t, 1H, JH3-H4=9.8, J=9.8, H4), 5.92 (dd or t, 1H, J=10.7, J=9.8, H4), 5.72 (dd, 1H, JH1-H2=2.0, JH2-H3=3.9, H2), 5.56 (dd, 1H, JH2-H3=2.9, H3), 5.33 (d, 1H, J=2.0, H1), 5.26 (dd, 1H, J=2.0, H2), 5.19 (d, 1H, J=2.0, J=3.9, H2), 5.16 (d, 1H, J=2.0, H1), 4.90 (d, 1H, H1), 4.78 and 4.62 (AB quartet, 2H, Jgem=11.7, CH2), 4.65-4.56 (m, 3H), 4.45 (dd, 1H, Jgem=12.7, JH5-H6=3.9, H6), 4.35 (dd, 1H, H3), 4.34-4.28 (m, 2H), 4.24 (dd, 1H, J=12.7, JH5-H6=2.9, H6), 4.10 (dt or dm, 1H, H5), 4.01 (dd, 1H, J=12.7, H6), 3.95 (dd, 1H, JH5-H6=2.0, H6).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08828952B2uspto-grants-2014_09