Reaktion #162024

ord-b0bfcd28ad6a42468f25c888b0e534fe

Reaktionsgleichung

[N-]=[N+]=NCCCO[C@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H](O[C@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)[C@H](O[C@H]3O[C@H](COC(=O)c4ccccc4)[C@@H](OC(=O)c4ccccc4)[C@H](OC(=O)c4ccccc4)[C@@H]3OC(=O)c3ccccc3)[C@@H]2OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
57
[N-]=[N+]=NCCCO[C@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H](O[C@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)[C@H](O[C@H]3O[C@H](COC(=O)c4ccccc4)[C@@H](OC(=O)c4ccccc4)[C@H](OC(=O)c4ccccc4)[C@@H]3OC(=O)c3ccccc3)[C@@H]2OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
3-Azidopropyl 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
C#CCO[C@H]1CC[C@@]2(C)C(CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CCCC(C)CO)[C@@]4(C)CC[C@@H]32)C1
3β-(prop-2-ynyloxy)cholestanol
O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O.[Na+]
sodium ascorbate
→
CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4C[C@@H](OCc5cn(CCCO[C@H]6O[C@H](COC(=O)c7ccccc7)[C@@H](OC(=O)c7ccccc7)[C@H](O[C@H]7O[C@H](COC(=O)c8ccccc8)[C@@H](OC(=O)c8ccccc8)[C@H](O[C@H]8O[C@H](COC(=O)c9ccccc9)[C@@H](OC(=O)c9ccccc9)[C@H](OC(=O)c9ccccc9)[C@@H]8OC(=O)c8ccccc8)[C@@H]7OC(=O)c7ccccc7)[C@@H]6OC(=O)c6ccccc6)nn5)CC[C@]4(C)[C@H]3CC[C@]12C
triazole
Ausbeute 72.0%
CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4C[C@@H](OCc5cn(CCCO[C@H]6O[C@H](COC(=O)c7ccccc7)[C@@H](OC(=O)c7ccccc7)[C@H](O[C@H]7O[C@H](COC(=O)c8ccccc8)[C@@H](OC(=O)c8ccccc8)[C@H](O[C@H]8O[C@H](COC(=O)c9ccccc9)[C@@H](OC(=O)c9ccccc9)[C@H](OC(=O)c9ccccc9)[C@@H]8OC(=O)c8ccccc8)[C@@H]7OC(=O)c7ccccc7)[C@@H]6OC(=O)c6ccccc6)nn5)CC[C@]4(C)[C@H]3CC[C@]12C
3-{4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl}propyl 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
Ausbeute 72.0%

Edukte

[N-]=[N+]=NCCCO[C@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H](O[C@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)[C@H](O[C@H]3O[C@H](COC(=O)c4ccccc4)[C@@H](OC(=O)c4ccccc4)[C@H](OC(=O)c4ccccc4)[C@@H]3OC(=O)c3ccccc3)[C@@H]2OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
57
[N-]=[N+]=NCCCO[C@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H](O[C@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)[C@H](O[C@H]3O[C@H](COC(=O)c4ccccc4)[C@@H](OC(=O)c4ccccc4)[C@H](OC(=O)c4ccccc4)[C@@H]3OC(=O)c3ccccc3)[C@@H]2OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
3-Azidopropyl 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
C#CCO[C@H]1CC[C@@]2(C)C(CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CCCC(C)CO)[C@@]4(C)CC[C@@H]32)C1
3β-(prop-2-ynyloxy)cholestanol
O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O.[Na+]
sodium ascorbate

Reagenzien

O=S(=O)([O-])[O-].[Cu+2]
CuSO4

Lösungsmittel

ClCCl
DCM
CC(C)(C)O
t-butanol

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeThe mixture was evaporated onto silica gel
  2. 2
    Sonstigepurified by silica column chromatography (2×14 cm, gradient elution with hexane-EtOAc 170:20, 150:30, 120:30, 120:40, 120:60, 120:80 and 100:100)

Vorschrift

To a mixture of 57 (81 mg, 0.0497 mol), 3β-(prop-2-ynyloxy)cholestanol (43 mg, 0.0994 mmol, 2 eq) in DCM (64 μL) and t-butanol (60 μL) (0.4 M) was added a solution of CuSO4 (0.3 M in water, 33 μL, 0.00994 mmol, 0.2 eq) and a solution of sodium ascorbate (1M in water, 20 μL, 0.0199 mmol, 0.4 eq). The mixture was vigorously stirred at r.t. for 3 days. The mixture was evaporated onto silica gel and purified by silica column chromatography (2×14 cm, gradient elution with hexane-EtOAc 170:20, 150:30, 120:30, 120:40, 120:60, 120:80 and 100:100) to give the triazole 58 as a colourless gum (74 mg, 72%). 1H NMR (CDCl3, 300 MHz) δ 8.19-7.88 (m, 16H, Bz), 7.69-7.15 (m, 35H, Bz and triazole-CH), 5.99 (dd or t, 1H, JH3-H4=9.9, JH4-H5=9.9, H4), 5.98 (dd or t, 1H, J=9.9, J=9.9, H4), 5.94 (dd or t, 1H, H4), 5.66 (dd, 1H, JH2(I)-H3(I)=3.1, JH1(I)H2(I)=1.6, H2I), 5.57 (dd, 1H, J3(III)-H4(III)=10.0, JH2(III)-H3(III)=3.1, H3III), 5.36 (d, 1H, JH1(II)-H2(II)=1.6, H1II), 5.28 (dd, 1H, JH2(II)-H3(II)=3.1, H2II), 5.21 (dd, 1H, JH1(III)-H2(III)=1.6, H2III), 5.04 (d, 1H, H1I), 4.94 (d, 1H, H1III), 4.70 (s, 2H, OCH2), 4.70-3.92 (m, 11H), 3.84 (dt or ddd, 1H, Jgem=9.9, J=6.3, J=6.3, OCH2), 3.50 (dt or ddd, 1H, J=5.5, J=5.5, OCH2), 3.37 (m, 1H, OCH-chol), 2.26 (m, 2H, CH2), 1.99-0.53 (m, 31H, cholestanyl), 0.90 (d, 3H, J=6.8, cholestanyl-CH3), 0.87 (d, 3H, J=6.8, cholestanyl-CH3), 0.86 (d, 3H, J=6.8, cholestanyl-CH3), 0.76 (s, 3H, cholestanyl-CH3), 0.64 (s, 3H, cholestanyl-CH3).

Quelle

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