Reference

1-N-[L(-)-

1-N-[L(-)-.gamma.-Amino-.alpha.-hydroxybutyryl]kanamycin derivatives. Miyano, Tetsuji (Banyu Pharmaceutical Co., Ltd., Japan). Japan. Kokai JP 51086445 29 Jul 1976 Showa, 8 pp.Chemicals with cas numbers 40371-50-4 and 40372-09-6 also play role. (Japanese). (Japan). CODEN: JKXXAF. CLASS: IC: C07H015-22. APPLICATION: JP 75-9700 24 Jan 1975. DOCUMENT TYPE: Patent CA Section: 33 (Carbohydrates) Section cross-reference(s): 63 The title compds. I (R = H, R1 = NH2, OH) were prepd. by treating 6'-N-acylkanamycin tri(or tetra)arylidene(or alkylidene) Schiff base [II, 6'-N-acyl = substituted-Z (Z = CO2CH2Ph), etc.] with (-)-R2NHCH2CH2CH(OH)CO2H (III, R2 = substituted-Z, etc.) and dicyclohexylcarbodiimide (IV, II:IV mole ratio = 1:0.3-1.5) or 1-ethyl-3-(N,N-dimethylamino-propyl)carbodiimide at 0-50.degree. in the presence of 1-hydroxybenztriazole (V) in a solvent followed by treatment with acid and hydrogenolysis of obtained I (R = acyl). II were prepd. by treating 6'-N-acylkanamycins with aldehyde (mole ratio = 1:>3). I (eg. amikacin) was effective against kanamycin resistant bacteria (no data). Thus, pH of 6'-N-Z-kanamycin A in MeOH was adjusted to 8.2 with dild. H2SO4, m-HOC6H4CHO added, the mixt. stirred 3 hr and kept overnight at room temp. to crystallize 6'-N-Z-1,3,3''-trisalicylidene-kanamycin A (VI). IV (24.3 g) in THF was added to a mixt. of 100 g VI, 27.2 g III (R2 = Z), and 1.35 g V in THF-H2O, the mixt. stirred 16 hr at 20.degree., acidified to pH 1.5 with HCl, and stirred 1 hr to give 18.2% VI 26.4% kanamycin A.H2SO4 salt, and I (R = acyl, R1 = OH), which on hydrogenolysis over 10% Pd-C gave 31.8% amikacin. .