Sulfuric Acid → (2R,4R,5R,6R,11S,13S,14R)-11-[(6-Deoxy-3-C-methyl-2,3,4-tri-O-methyl-alpha-L-mannopyranosyl)oxy]-4-(dimethylamino)-3,5,8,10,13-pentahydroxy-6,13-dimethyl-9,16-dioxo-3,4,5,6,9,11,12,13,14,16-decahydro-2H-2,6-epoxytetraceno[1,2-b]oxocine-14-carboxylic acid (incorrect configuration definition!)

HRID 461937Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 461937
[CH3:1][C@@H:2]1[O:7][C@@H:6]([O:8][C@@H:9]2[C:14]3[C:15]([OH:43])=[C:16]4[C:41](=[O:42])[C:22]5[C:23]([OH:40])=[CH:24][C:25]6[C@@:32]7([CH3:34])[O:33][C@H:28]([C@@H:29]([OH:39])[C@H:30]([N:36]([CH3:38])[CH3:37])[C@H:31]7[OH:35])[O:27][C:26]=6[C:21]=5[C:19](=[O:20])[C:17]4=[CH:18][C:13]=3[C@@H:12]([C:44]([O:46]C)=[O:45])[C@:11]([OH:49])([CH3:48])[CH2:10]2)[C@H:5]([O:50][CH3:51])[C@@:4]([O:53][CH3:54])([CH3:52])[C@H:3]1[O:55][CH3:56].[OH-].[K+].OS(O)(=O)=O>CCO.CO.O.C(Cl)(Cl)Cl>[CH3:1][C@@H:2]1[O:7][C@@H:6]([O:8][C@@H:9]2[C:14]3[C:15]([OH:43])=[C:16]4[C:41](=[O:42])[C:22]5[C:23]([OH:40])=[CH:24][C:25]6[C@@:32]7([CH3:34])[O:33][C@H:28]([C@@H:29]([OH:39])[C@H:30]([N:36]([CH3:38])[CH3:37])[C@H:31]7[OH:35])[O:27][C:26]=6[C:21]=5[C:19](=[O:20])[C:17]4=[CH:18][C:13]=3[C@@H:12]([C:44]([OH:46])=[O:45])[C@:11]([OH:49])([CH3:48])[CH2:10]2)[C@H:5]([O:50][CH3:51])[C@@:4]([O:53][CH3:54])([CH3:52])[C@H:3]1[O:55][CH3:56]

Komponenten

8

Edukt 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 5289019Nogalamycin

Produkt 1

HCID 152473(2R,4R,5R,6R,11S,13S,14R)-11-[(6-Deoxy-3-C-methyl-2,3,4-tri-O-methyl-alpha-L-mannopyranosyl)oxy]-4-(dimethylamino)-3,5,8,10,13-pentahydroxy-6,13-dimethyl-9,16-dioxo-3,4,5,6,9,11,12,13,14,16-decahydro-2H-2,6-epoxytetraceno[1,2-b]oxocine-14-carboxylic acid (incorrect configuration definition!)

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittel2×HCID 962WaterLösungsmittel2×HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

Forty grams (0.05 mole) of nogalamycin was dissolved in 356 ml of 1 N KOH (0.36 mole), and 310 ml of water was added. The solution was stirred overnight at room temperature. The reaction mixture was acidified to pH 3.0 by adding 30% H2SO4 dropwise with stirring. The precipitate was collected by centrifugation and the precipitate was washed three times with water. The dried product weighted 28.5 g. Ten grams was dissolved in 125 ml of methanol and put on 500 g of silica packed in CHCl3 --MeOH (95:5). Developed with CHCl3 --MeOH (95:5) increasing gradually to CHCl3 --MeOH (4:1). Elution was continued with CHCl3 --MeOH (1:1) until nogalamycinic acid had been eluted as determined by thin layer chromatography (tlc) using CHCl3 --MeOH--H2O (78:20:2). Evaporation in vacuo of the fractions containing chromatographically pure material gave a red solid, wt. 2.3 g; mp 219°-229° C.; Rf (tlc, CHCl3 --MeOH--H2O; 78:20:2) 0.25; αD +456° (C 0.37, CH3OH); uv (EtOH) λmax nm 236 (ε 39,950), 269 (ε 21,350), 291 sh (ε 8,700), 482 (13,550); ir (Nujol) 3450, 1670, 1630, 1595, 1580, 1290, 1230, 1215, 1135, 1095, 1060, 1015, 980, 920, 855, 830, 780, 763 and 725 cm-1 ; mass spectrum m/e 729 (M- --CO2); 'H NMR (CDCl3 --CD3OD) δ 1.38 (m, 9 H, 3 CH3C), δ 1.80 (s, 3 H, CH3C), δ 3.15 (s, 6H, (CH3)2NH+), δ 3.38, 3.40, 3.68 (3 s, 9 H, 3 CH3O), δ 3.2-4.0 (m, CHO and CHN), δ 5.24 (d, 1 H, anomeric), δ 5.88 (d, 1 H, anomeric), δ 6.92 (s, 1 H, aromatic) and δ 7.47 (s, 1 H, aromatic); 13C NMR (CDCl3 --CD2OD) 16.4, 19.3, 24.6, 31.5 (4 CH3C), δ 42.5 [(CH3)2N], δ 49.9, 58.2, 60.3, 62.5, 67.8, 68.5, 70.6, 71.6, 74.0, 77.3, 79.6, 82.1 and 85.9 (CH3O, CHO and CHN), δ 97.3 and 100.2 (anomeric), δ 113.1, 114.1, 116.0, 120.7, 125.8, 131.0, 132.5, 137.2, 147.4, 147.8, 156.0 and 161.4 (aromatic), δ 178.9, 181.9, 181.6 and 191.4 (carbonyl).

Aufarbeitung

  1. stirringwith stirring
  2. customThe precipitate was collected by centrifugation
  3. washthe precipitate was washed three times with water
  4. dissolutionTen grams was dissolved in 125 ml of methanol
  5. temperatureDeveloped with CHCl3 --MeOH (95:5) increasing gradually to CHCl3 --MeOH (4:1)
  6. washElution
  7. washhad been eluted
  8. customEvaporation in vacuo of the fractions
  9. additioncontaining chromatographically pure material
  10. customgave a red solid, wt. 2.3 g

Quellen und Nachweise

ORD-Eintrag
ord-4dbe465505c74c44b95c63432e621e8a
Quelldatensatz
uspto-grants-1977_12
Patentnummer
US04064340

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