(6R,6aS,14aR)-methyl 1-(2-(benzyloxy)-2-oxoethoxy)-6,8,14a-trihydroxy-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 → 2-((6R,6aS,14aR)-6,8,14a-trihydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-2-(methoxycarbonyl)-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracen-1-yloxy)acetic acid

HRID 406136Notes

Reaction equation

HRID 406136 reaction equation
C([O:8][C:9](=[O:61])[CH2:10][O:11][C:12]1[C:17]2[C@@:18]3([OH:55])[C@@:31]([O:35][CH3:36])([C@H:32]([OH:34])[CH2:33][C:16]=2[CH:15]=[C:14]([CH3:56])[C:13]=1[C:57]([O:59][CH3:60])=[O:58])[C:30](=[O:37])[C:29]1[C:20](=[CH:21][C:22]2[C:23](=[O:53])[C:24]([NH:40][C@@H:41]4[C@H:46]([O:47][CH3:48])[C@H:45]([OH:49])[C@@H:44]([O:50][CH3:51])[C@H:43]([CH3:52])[O:42]4)=[CH:25][C:26](=[O:39])[C:27]=2[C:28]=1[OH:38])[C:19]3=[O:54])C1C=CC=CC=1>C1COCC1.[Pd]>[OH:34][C@H:32]1[C@:31]2([O:35][CH3:36])[C@@:18]([OH:55])([C:19](=[O:54])[C:20]3[C:29]([C:30]2=[O:37])=[C:28]([OH:38])[C:27]2[C:26](=[O:39])[CH:25]=[C:24]([NH:40][CH:41]4[C@H:46]([O:47][CH3:48])[C@H:45]([OH:49])[C@@H:44]([O:50][CH3:51])[C@H:43]([CH3:52])[O:42]4)[C:23](=[O:53])[C:22]=2[CH:21]=3)[C:17]2[C:12]([O:11][CH2:10][C:9]([OH:61])=[O:8])=[C:13]([C:57]([O:59][CH3:60])=[O:58])[C:14]([CH3:56])=[CH:15][C:16]=2[CH2:33]1

Participants

4

Reactant 1

HCID 56601789(6R,6aS,14aR)-methyl 1-(2-(benzyloxy)-2-oxoethoxy)-6,8,14a-trihydroxy-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

Product 1

HCID 671214372-((6R,6aS,14aR)-6,8,14a-trihydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-2-(methoxycarbonyl)-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracen-1-yloxy)acetic acidYield 71.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (6R,6aS,14aR)-methyl 1-(2-(benzyloxy)-2-oxoethoxy)-6,8,14a-trihydroxy-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 (22 mg, 0.024 mmol) and 10% Pd/C (10 mg) in THF (1 mL) was stirred under hydrogen (1 atm) at room temperature for 1 h. The reaction mixture was filtered and concentrated. The residue was purified by semi-preparative HPLC (45:55 acetonitrile/water with 0.05% TFA) to afford 2-((6R,6aS,14aR)-6,8,14a-trihydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-2-(methoxycarbonyl)-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracen-1-yloxy)acetic acid (13 mg, 66%) as an orange solid and as a mixture of diastereomers: 1H NMR (500 MHz, acetone-d6) δ 14.30 (br s, 1H), 8.21 (s, 0.5H), 8.17 (s, 0.5H), 7.19 (d, J=9.0 Hz, 0.5H), 7.08 (d, J=5.7 Hz, 0.5H), 6.99 (s, 0.5H), 6.91 (s, 0.5H), 6.17 (s, 0.5H), 6.00 (s, 0.5H), 5.30 (br s, 1H), 5.11 (d, J=4.8 Hz, 0.5H), 5.06 (d, J=4.8 Hz, 0.5H), 4.92-4.85 (m, 0.5H), 4.76-4.72 (m, 0.5H), 4.62 (br s, 0.5H), 4.60 (br s, 0.5H), 4.50-4.41 (m, 1H), 4.04 (d, J=5.1 Hz, 1H), 3.91-3.83 (m, 1H), 3.76 (s, 1.5H), 3.75 (s, 1.5H), 3.74 (br s, 3H), 3.54 (br s, 3H), 3.52 (s, 1.5H), 3.50 (s, 1.5H), 3.32-3.30 (m, 1H), 3.09-3.05 (m, 1H), 2.19 (s, 1.5H), 2.17 (s, 1.5H), 1.25 (d, J=6.2 Hz, 1.5H), 1.21 (d, J=6.3 Hz, 1.5H); MS (ESI+) m/z 756 (M+H); HPLC 98.5% (AUC), tR 11.48, 11.45 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. customThe residue was purified by semi-preparative HPLC (45:55 acetonitrile/water with 0.05% TFA)

Sources & evidence

ORD record
ord-c7b0b225186242c6aea23d0ba57770a0
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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