Dicyclohexylcarbodiimide → t-Butyldimethylsilyl 6-O-{3-O-allyloxycarbonyl-6-O-benzyl-2-deoxy-4-O-(1,5-dihydro-3-oxo-3lambda5-3H-2,4,3-benzodioxaphosphepin-3yl)-2-[(R)-3-dodecanoyloxy-tetradecanoylamino]-beta-D-glucopyranosyl}-2-azido-4-O-benzyl-3-O-[(R)-3-benzyloxy-tetradecanoyl]-2-deoxy-beta-D-glucopyranoside

HRID 628193Notes

Reaction equation

HRID 628193 reaction equation
[CH2:1]([O:8][C@H:9]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:10][C:11]([OH:13])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH2:40]([O:43][C:44]([O:46][C@H:47]1[C@H:52]([O:53][P:54]2(=[O:65])[O:60][CH2:59][C:58]3[CH:61]=[CH:62][CH:63]=[CH:64][C:57]=3[CH2:56][O:55]2)[C@@H:51]([CH2:66][O:67][CH2:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[O:50][C@@H:49]([O:75][CH2:76][C@H:77]2[O:90][C@@H:81]([O:82][Si:83]([C:86]([CH3:89])([CH3:88])[CH3:87])([CH3:85])[CH3:84])[C@H:80]([N:91]=[N+:92]=[N-:93])[C@@H:79](O)[C@@H:78]2[O:95][CH2:96][C:97]2[CH:102]=[CH:101][CH:100]=[CH:99][CH:98]=2)[C@@H:48]1[NH:103][C:104](=[O:132])[CH2:105][C@H:106]([O:118][C:119](=[O:131])[CH2:120][CH2:121][CH2:122][CH2:123][CH2:124][CH2:125][CH2:126][CH2:127][CH2:128][CH2:129][CH3:130])[CH2:107][CH2:108][CH2:109][CH2:110][CH2:111][CH2:112][CH2:113][CH2:114][CH2:115][CH2:116][CH3:117])=[O:45])[CH:41]=[CH2:42]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:40]([O:43][C:44]([O:46][C@H:47]1[C@H:52]([O:53][P:54]2(=[O:65])[O:60][CH2:59][C:58]3[CH:61]=[CH:62][CH:63]=[CH:64][C:57]=3[CH2:56][O:55]2)[C@@H:51]([CH2:66][O:67][CH2:68][C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[O:50][C@@H:49]([O:75][CH2:76][C@H:77]2[O:90][C@@H:81]([O:82][Si:83]([C:86]([CH3:87])([CH3:89])[CH3:88])([CH3:84])[CH3:85])[C@H:80]([N:91]=[N+:92]=[N-:93])[C@@H:79]([O:12][C:11](=[O:13])[CH2:10][C@H:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C@@H:78]2[O:95][CH2:96][C:97]2[CH:98]=[CH:99][CH:100]=[CH:101][CH:102]=2)[C@@H:48]1[NH:103][C:104](=[O:132])[CH2:105][C@H:106]([O:118][C:119](=[O:131])[CH2:120][CH2:121][CH2:122][CH2:123][CH2:124][CH2:125][CH2:126][CH2:127][CH2:128][CH2:129][CH3:130])[CH2:107][CH2:108][CH2:109][CH2:110][CH2:111][CH2:112][CH2:113][CH2:114][CH2:115][CH2:116][CH3:117])=[O:45])[CH:41]=[CH2:42]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 11110428(R)-3-(Benzyloxy)tetradecanoic acidHCID 16216230t-Butyldimethylsilyl 6-O-{3-O-allyloxycarbonyl-6-O-benzyl-2-deoxy-4-O-(1,5-dihydro-3-oxo-3lambda5-3H-2,4,3-benzodioxaphosphepin-3yl)-2-[(R)-3-dodecanoyloxy-tetradecanoylamino]-beta-D-glucopyranosyl}-2-azido-4-O-benzyl-2-deoxy-beta-D-glucopyranoside

Product 1

HCID 16216359t-Butyldimethylsilyl 6-O-{3-O-allyloxycarbonyl-6-O-benzyl-2-deoxy-4-O-(1,5-dihydro-3-oxo-3lambda5-3H-2,4,3-benzodioxaphosphepin-3yl)-2-[(R)-3-dodecanoyloxy-tetradecanoylamino]-beta-D-glucopyranosyl}-2-azido-4-O-benzyl-3-O-[(R)-3-benzyloxy-tetradecanoyl]-2-deoxy-beta-D-glucopyranosideYield 86%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A reaction mixture of (R)-3-benzyloxy-tetradecanoic acid 15 (100 mg, 0.293 mmol) and DCC (93 mg, 0.450 mmol) in DCM (5 mL) was stirred at room temperature for 10 min, and then disaccharide 21 (300 mg, 0.225 mmol) in DCM (3 mL) and DMAP (11 mg, 0.090 mmol) were added. The reaction mixture was stirred at room temperature for 14 h, after which the solids were removed by filtration, and the residue washed with DCM (2×1 mL). The combined filtrates were concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate, 4/1, v/v) to give 22 as a white solid (319 mg, 86%). Rf=0.41 (hexane/ethyl acetate, 2/1, v/v). [α]26D=−2.8° (c=1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ 7.33-7.15 (m, 19H, aromatic), 5.94-5.85 (m, 2H, NH, OCH2CH═CH2), 5.45 (t, 1H, J2′,3′=J3′,4′=9.5 Hz, H-3′), 5.34 (d, 1H, J=17.5 Hz, OCH2CH═CH2), 5.22 (d, 1H, J=10.0 Hz, OCH2CH═CH2), 5.08-4.95 (m, 7H, H-1, H-3, H-3L, C6H4(CH2O)2P), 4.61-4.44 (m, 10H, H-1, H-4′, 3×CH2Ph, OCH2CH═CH2), 3.96 (d, 1H, J6′a,6′b=10.5 Hz, H-6′a), 3.88-3.85 (m, 1H, H-3S), 3.80 (d, 1H, J6a,6b=9.5 Hz, H-6a), 3.72-3.66 (m, 3H, H-5′, H-6b, H-6′b), 3.55-3.52 (m, 2H, H-4, H-5), 3.47-3.41 (m, 1H, H-2′), 3.27 (dd, 1H, J1,2=7.5 Hz, J2,3=10.0 Hz, H-2), 2.56 (dd, 1H, J2Sa,2Sb=16.0 Hz, J2Sa,3S=7.0 Hz, H-2Sa), 2.43 (dd, 1H, J2Sa,2Sb=16.0 Hz, J2Sb,3S=7.0 Hz, H-2Sb), 2.35 (dd, 1H, J2La,2Lb=15.0 Hz, J2La,3L=6.0 Hz, H-2La), 2.30-2.20 (m, 3H, H-2L′, H-2L′b), 1.59-1.52 (m, 6H, H-4L, H-4S, H-3L′), 1.23 (broad, 52H, 26×CH2, lipid), 0.90 (s, 9H, SiC(CH3)3), 0.88-0.84 (m, 9H, 3×CH3, lipid), 0.12 (s, 6H, Si(CH3)2). 13C NMR (75 MHz, CDCl3): δ 173.40 (C═O), 170.55 (C═O), 169.94 (C═O), 154.42 (C═O), 138.46-127.35 (aromatic, OCH2CH═CH2), 118.74 (OCH2CH═CH2), 99.29 (C-1′), 96.96 (C-1), 75.89, 75.62, 74.75, 74.28, 74.02, 73.67, 73.41, 71.34, 70.89, 68.87-67.85 (m), 66.48, −4.18 (Si(CH3)2), −5.38 (Si(CH3)2). HR MS (m/z) calculated for C91H139N4O19Psi[M+Na]+, 1673.9438. found, 1674.1754.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 14 h
  2. customafter which the solids were removed by filtration
  3. washthe residue washed with DCM (2×1 mL)
  4. concentrationThe combined filtrates were concentrated in vacuo
  5. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate, 4/1

Sources & evidence

ORD record
ord-9aa614a2fc164cefaa96d247f5fd6841
Source dataset
uspto-grants-2016_04
Patent number
US09309276B2

Reaction notes

Loading…