Azide → 3-{4-(Cholestan-3beta-yl-oxymethyl)-[1,2,3]triazol-1-yl}propyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-alpha-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-alpha-D-mannopyranoside

HRID 74837

Reaction equation

HRID 74837 reaction equation
[CH2:1]([O:4][C@H:5]1[CH2:30][CH2:29][C@@:28]2([CH3:31])[CH:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:32])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C@H:15]([CH3:23])[CH2:16][CH2:17][CH2:18][CH:19]([CH3:22])[CH2:20]O)[CH2:6]1)[C:2]#[CH:3].[C:33]([O:36][C@H:37]1[C@@H:42]([O:43][C:44](=[O:46])[CH3:45])[C@H:41]([O:47][C:48](=[O:50])[CH3:49])[C@@H:40]([CH2:51][O:52][C:53](=[O:55])[CH3:54])[O:39][C@@H:38]1[O:56][C@H:57]1[C@H:62]([O:63][C:64](=[O:66])[CH3:65])[C@@H:61]([CH2:67][O:68][C:69](=[O:71])[CH3:70])[O:60][C@H:59]([O:72][C@H:73]2[C@@H:85]([O:86][C:87](=[O:89])[CH3:88])[C@H:84]([O:90][C:91](=[O:93])[CH3:92])[C@@H:83]([CH2:94][O:95][C:96](=[O:98])[CH3:97])[O:82][C@@H:74]2[O:75][CH2:76][CH2:77][CH2:78][N:79]=[N+:80]=[N-:81])[C@H:58]1[O:99][C:100](=[O:102])[CH3:101])(=[O:35])[CH3:34].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[N-]=[N+]=[N-]>C(Cl)Cl.CC(O)(C)C.C(Cl)Cl.[O-]S([O-])(=O)=O.[Cu+2].CCOC(C)=O.C1(C)C=CC=CC=1>[C:33]([O:36][C@H:37]1[C@@H:42]([O:43][C:44](=[O:46])[CH3:45])[C@H:41]([O:47][C:48](=[O:50])[CH3:49])[C@@H:40]([CH2:51][O:52][C:53](=[O:55])[CH3:54])[O:39][C@@H:38]1[O:56][C@H:57]1[C@H:62]([O:63][C:64](=[O:66])[CH3:65])[C@@H:61]([CH2:67][O:68][C:69](=[O:71])[CH3:70])[O:60][C@H:59]([O:72][C@H:73]2[C@@H:85]([O:86][C:87](=[O:89])[CH3:88])[C@H:84]([O:90][C:91](=[O:93])[CH3:92])[C@@H:83]([CH2:94][O:95][C:96](=[O:98])[CH3:97])[O:82][C@@H:74]2[O:75][CH2:76][CH2:77][CH2:78][N:79]2[CH:3]=[C:2]([CH2:1][O:4][C@H:5]3[CH2:30][CH2:29][C@@:28]4([CH3:31])[CH:7]([CH2:8][CH2:9][C@@H:10]5[C@@H:27]4[CH2:26][CH2:25][C@@:24]4([CH3:32])[C@H:11]5[CH2:12][CH2:13][C@@H:14]4[C@H:15]([CH3:23])[CH2:16][CH2:17][CH2:18][CH:19]([CH3:20])[CH3:22])[CH2:6]3)[N:81]=[N:80]2)[C@H:58]1[O:99][C:100](=[O:102])[CH3:101])(=[O:35])[CH3:34]

Participants

10

Reactant 4

HCID 33558AzideHCID 23667548Sodium AscorbateHCID 866582823beta-(Prop-2-ynyloxy)cholestanolHCID 1317318573-Azidopropyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-alpha-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-alpha-D-mannopyranoside

Product 1

HCID 1317318563-{4-(Cholestan-3beta-yl-oxymethyl)-[1,2,3]triazol-1-yl}propyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-alpha-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-alpha-D-mannopyranosideYield 81.5%

Reagents, catalysts & solvents 5

HCID 24462Copper SulfateCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 18914702t-Butanol dichloromethaneSolvent

Procedure

3β-(Prop-2-ynyloxy)cholestanol (156 mg, 2 eq., 0.367 mmol) and the azide 45 (185 mg, 0.183 mmol) were dissolved in a mixture of DCM/t-BuOH (3:2, w/w, 0.4 M, 0.562 mL). To the mixture were added an aqueous solution of CuSO4 (0.3 M, 0.1 eq., 0.061 mL) and a aqueous solution of sodium ascorbate (1 M, 0.3 eq., 0.055 mL) and the mixture was vigorously stirred without light for 48 h. TLC analysis (toluene:EtOAc, 1:1) showed the end of the reaction with the appearance of a more polar product than the starting azide. The mixture was diluted with DCM (50 mL) and washed with satd. NaHCO3-solution (3×30 mL). The aqueous phase was re-extracted with EtOAc (3×20 mL), organic extracts were combined, washed with brine (20 mL), dried (Na2SO4) and concentrated in vacuo to afford the crude product as a yellow foam (475 mg). The crude product was purified on a column of silica gel (25×2.5 cm, toluene—EtOAc, 1:2→1:3→1:4) to yield the triazole 46 as white foam (214 mg, 81%). 1H NMR (CDCl3, 400 MHz) δ 7.76 (s, 1H, ═CH), 5.18-5.36 (m, 6H, 3×H4, H2II, H3I, H3III), 5.06 (dd 1H, JH2-H3=3.2, H2III), 5.02 (d, 1H, JHI-H2=1.7, H1III), 4.94 (d, 2H, JHI-H2=1.6, H-1II), 4.92 (d, 1H, JHI-H2=1.6, H1I), 4.71 (s, 2H, OCH2), 4.49 (t, 2H, J=6.6, CH2N), 4.30 (dd, 1H, JH6a-H6b=−11.9, JH6-H5=4.0, H6a), 3.96-4.26 (m, 9H, 2×H6a, 3×H6b, H2I, H3II, H5I, H5II or H5III), 3.92 (ddd, 1H, H5II or H5III), 3.43 (m, 2H, OCH2, H-3 Chol), 2.31 (m, 2H, CH2), 2.19, 2.145, 2.142, 2.11, 2.09, 2.08, 2.06, 2.04, 1.99 (s, 30H, 10×Ac), 1.90 (quintet, 2H, J=6.6, CH2), 0.56-2.04 (m, 33H, 12CH2, 9CH), 0.89 (d, 3H, J=6.8, cholestanyl-CH3), 0.858 (d, 3H, J=6.8, cholestanyl-CH3), 0.855 (d, 3H, J=6.8, cholestanyl-CH3), 0.79 (s, 3H, cholestanyl-CH3), 0.64 (s, 3H, cholestanyl-CH3).

Workup

  1. washwashed with satd
  2. extractionThe aqueous phase was re-extracted with EtOAc (3×20 mL), organic extracts
  3. washwashed with brine (20 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product as a yellow foam (475 mg)
  7. customThe crude product was purified on a column of silica gel (25×2.5 cm, toluene—EtOAc, 1:2→1:3→1:4)

Sources & evidence

ORD record
ord-0b35c7df7c58466db9dec45c905fd8be
Source dataset
uspto-grants-2014_09
Patent number
US08828952B2

Linked notes

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