17-Aminodemethoxygeldanamycin synthesis

Yield:64202-81-9 95%

Reaction Conditions:

with ammonia in water;acetonitrile at 20; for 5 h;

Steps:

4

17-Amino-17-demethoxvgeldanamycin (6) (Schnur et al., 1995b; Li, LH et al., 1977; Sasaki, K et al., 1979). Concentrated aqueous solution of ammonia (28%, 0.70 ml, 0.010 mol) was added to a solution of (+) -geldanamycin (5.0 mg, 9. 0 umol) in acetonitrile (5.0 ml) at room temperature. The yellow solution turned slowly dark red. Upon the complete conversion of GA shown by thin layer chromatography (5 hours), the mixture was partitioned between ethyl acetate and brine. The organic phase was washed with brine, dried over anhydrous sodium sulfate, and concentrated. Separation of the solid residue by flash column chromatography on silica gel (hexane/ethyl acetate) gave the product as a dark red solid (4.6 mg, 95%). IR (KBr) (cm'') 3452,3339, 2957,2931, 2825,1721, 1692, 1617, 1591,1495, 1374,1323, 1250,1190, 1133,1101, 1055; UV (95% EtOH) (nm) 328 (s = 2.0 x 104) ;'H NMR (CDCl3, 500 MHz) 8 9.08 (s, 1H), 7.26 (s, 1H), 6.95 (bd, J= 11.5 Hz, 1H), 6.56 (bdd, J= 11.5, 11.0 Hz, 1H), 5.89-5. 82 (m, 2H), 5.37 (bs, 2H), 5.17 (s, 1H), 4.73 (bs, 2H), 4.29 (bd, J= 10.0 Hz, 1H), 3.98 (bs, 1H), 3.59 (ddd, J= 9.0, 6.5, 2.0 Hz, 1H), 3.42 (ddd, J= 9.0, 3.0, 3.0 Hz, 1H), 3.34 (s, 3H), 3.25 (s, 3H), 2.75 (dqd, J= 9.5, 7.0, 2.0 Hz, 1H), 2.65 (d, J= 14.0 Hz, 1H), 2.01 (bs, 3H), 1.97-1. 75 (m, 4H), 1.79 (d, J= 1.0 Hz, 3H), 0.99-0. 97 (m, 6H) ; 13C NMR (CDC13, 125 MHz) # 183.1, 180.4, 167.9, 156.1, 146.0, 140.4, 135.8, 135.0, 134.0, 133.0, 126.9, 126.6, 110.3, 108. 6,81. 9,81. 2,81. 1,72. 2,57. 1,56. 8,35. 0,34. 7,32. 2,28. 7,23. 8,12. 8,12. 5,12. 2; HRMS (FAB) found 546.2818 [M+H]', caled. 546. 2816 for C28H4oN308.

References:

WO2005/95347,2005,A1 Location in patent:Page/Page column 34; 35