(6R,6aS,14aR)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate → HCID 56601391, compound

HRID 406167Notes

Reaction equation

HRID 406167 reaction equation
[OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([O:49][CH3:50])=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][C@@H:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15][C:16](=[O:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].[C:51]1([Mg]Br)[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>C1COCC1>[OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([O:49][CH3:50])=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13]([OH:43])([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[C:14]([NH:30][C@@H:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15][C:16](=[O:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44]

Participants

4

Reactant 2

HCID 67121454(6R,6aS,14aR)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylateHCID 178418255HCID 178418255, compound

Product 1

HCID 56601391HCID 56601391, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of (6R,6aS,14aR)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (50 mg, 0.072 mmol) in THF (2 mL) was added a solution of phenylmagnesium bromide in THF (1M, 0.72 mL, 0.72 mmol) dropwise. The reaction mixture was stirred at −78° C. for 3 h, and then quenched with a saturated solution of ammonium chloride. The mixture was extracted with chloroform (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude was purified by preparative TLC (silica gel, 95:5 chloroform/methanol) twice to afford (6R,6aS,14aR)-methyl 1,6,8,12,14a-pentahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,14-trioxo-12-phenyl-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (diastereomer A, 8 mg, 14%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 15.16 (s, 1H), 11.96 (s, 1H), 7.62 (s, 1H), 7.56-7.53 (m, 2H), 7.37-7.29 (m, 3H), 6.52 (s, 1H), 6.26 (d, J=8.5 Hz, 1H), 5.66 (s, 1H), 5.19 (s, 1H), 4.94 (t, J=6.5 Hz, 1H), 4.70 (d, J=9.5 Hz, 1H), 4.64 (d, J=8.5 Hz, 1H), 3.80 (s, 3H), 3.65 (s, 4H), 3.60-3.52 (m, 2H), 3.52 (s, 3H), 3.39 (s, 3H), 3.35-3.13 (m, 3H), 3.00 (t, J=9.0 Hz, 1H), 2.48 (d, J=4.0 Hz, 1H), 2.38 (s, 3H), 1.24 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 776 (M+H); HPLC 97.5% (AUC), tR 13.23 min; and (6R,6aS,14aR)-methyl 1,6,8,12,14a-pentahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,14-trioxo-12-phenyl-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (diastereomer B, 5 mg, 9%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 15.07 (s, 1H), 11.58 (s, 1H), 7.51 (s, 1H), 7.37-7.35 (m, 2H), 7.28-7.24 (m, 3H), 6.48 (s, 1H), 6.31 (d, J=9.0 Hz, 1H), 5.64 (s, 1H), 5.16 (s, 1H), 4.95 (t, J=6.5 Hz, 1H), 4.70-4.62 (m, 2H), 3.81 (s, 3H), 3.56 (s, 4H), 3.60-3.45 (m, 2H), 3.39 (s, 3H), 3.38 (s, 3H), 3.35-3.17 (m, 3H), 3.02 (t, J=9.0 Hz, 1H), 2.36 (s, 4H), 1.31 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 776 (M+H); HPLC 93.7% (AUC), tR 12.64 min.

Workup

  1. customquenched with a saturated solution of ammonium chloride
  2. extractionThe mixture was extracted with chloroform (3×15 mL)
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by preparative TLC (silica gel, 95:5 chloroform/methanol) twice

Sources & evidence

ORD record
ord-621a87fd13ad41309861a558187fa759
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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