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 461937Notes

Reaction equation

HRID 461937 reaction equation
[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]

Participants

8

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 5289019Nogalamycin

Product 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!)

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4dbe465505c74c44b95c63432e621e8a
Source dataset
uspto-grants-1977_12
Patent number
US04064340

Reaction notes

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