Реакция #172893

ord-051becbae45c414caf8a2ccb979a8349

Уравнение реакции

C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)OCc8ccccc8)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
(2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate
C[SiH](C)C(C)(C)C
tert-butyldimethylsilane
CCN(CC)CC
triethylamine
CCCC[N+](CCCC)(CCCC)CCCC.[F-]
TBAF
→
C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
desired product
Выход 52.0%
C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
(2S,3S,4S,5R,6R)-6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid
Выход 52.0%

Реактанты

C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)OCc8ccccc8)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
(2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate
C[SiH](C)C(C)(C)C
tert-butyldimethylsilane
CCN(CC)CC
triethylamine
CCCC[N+](CCCC)(CCCC)CCCC.[F-]
TBAF

Реагенты

CC(=O)[O-].CC(=O)[O-].[Pd+2]
palladium acetate

Растворители

CC(Cl)Cl
dichloroethane
C1CCOC1
THF

Условия реакции

Температура
60°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    ТемператураThe reaction mixture was cooled to room temperature
  2. 2
    Фильтрацияfiltered
  3. 3
    Концентрированиеthe filtrates were concentrated
  4. 4
    Другоеto provide the residue
  5. 5
    ДругоеThe reaction mixture was then purified by prep

Методика

A mixture of (2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate (8 mg, 8.36 mmol), tert-butyldimethylsilane (1.943 mg, 0.017 mmol), palladium acetate (3.75 mg, 0.017 mmol) and triethylamine (5.82 μl, 0.042 mmol) in dichloroethane (1 mL) was heated up at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, filtered and the filtrates were concentrated to provide the residue. To this residue in THF (1.0 mL) was added TBAF (10.93 mg, 0.042 mmol), the reaction mixture was stirred for 1 hours. The reaction mixture was then purified by prep. HPLC to provide the desired product as a colorless oil (4 mg, 52%). LCMS: m/e 867.69 (M+H)+, 2.42 min (method 10). 1H NMR (500 MHz, Acetic) δ 8.06 (d, J=8.2 Hz, 2H), 7.31 (d, J=8.2 Hz, 2H), 5.96 (d, J=7.9 Hz, 1H), 5.37 (d, J=4.4 Hz, 1H), 4.84 (s, 1H), 4.74 (s, 1H), 4.40-4.16 (m, 1H), 4.02-3.76 (m, 3H), 3.46 (d, J=12.3 Hz, 1H), 3.37-3.22 (m, 6H), 3.20-3.11 (m, 3H), 3.07 (br. s., 2H), 3.00-2.82 (m, 1H), 2.37-1.03 (m, 22H), 1.76 (s, 3H), 1.29 (s, 3H), 1.14 (s, 3H), 1.10 (s, 3H), 1.02 (s, 3H), 0.99 (s, 3H).

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US08846647B2uspto-grants-2014_09