SU511007A3 - The method of obtaining 3,4 dideoxyanamycin in - Google Patents

Claims (1)

1H, alkyl, aralkyl spp: -that group; BUT . X - nlc g (GL L KA1:; -; 1; TSC, COOTSeiCTBaHi-IO, H ..% LCLL: H; a aryl1-g, s. Rpyiino: i) nlp (CH) j; C , 5 or b; Y, ::: - c; k in gz 1 are, sotsgvek o, YHOMS asdoroda, alkg-sh- or arylnok POY) Kli (cT 2n1 h 5 or 6; 2. -and:, ShlTalkyl, ara / lived, aryl 5; g , arsl klc sulfonic NLP arnlsulfonyl group .. Derived formula 1 or 1 eate is converted into a derivative, as shown on the general formula-C 2 Sy, KHS05 (# 1 / K-SP2) -O j6OL -.) i J Ifm MPJI {(/ “K-CH8) OCH, l-CHRNl / oY liljX where W is H, alnyl sulfosh, arylsulfonyl or aryshsulfonnlya group,,, are those x, e, th. The formula is described or 1. As shown in the general formula 2 (where C is an alkln, aralkyl or aryl group) is 3- and 4-gcdroc c1-u.nn groups of hets sulfoalkylsBannki n, Derivative 2 (-SQ.jQ) SETS;.: treated with iodine ion and posozuicoQC-pasKKM metal, possessing SEON reduction properties, such as dusts, in a suitable solvent with such a calculation, so pap - Iggt W, 4-unsaturated group. After the {-1ya grouping of the images of the aircraft, after the hydrogenation of the nether carcass, the usual oSpasoM are removed to obtain the target product 3, 4-dideoxy oxamycin B. Example 1. Synthesis of penta xycaonal alkanamine B. To a mixture of 1.0 G cannabis: -gd .-; and B as a free base and Gf9 g of anhydrous sodium carbonate ij 20, ml of a mixture of acetone and water (ill), add 1.05 ml of ethoxycarbol; lcloride and continuing ; from recirculation for 5 hours; room temperature, O & s precipitates are filtered out, filtered with water, and BbTcj-iaHsatO 1.40 g of tea is obtained rdogo ketstva, gp:. ZS5S (with designation) Dss svPS fC-0,5, d.metklformamide). PRI me R 2 Synthesis of peit-m-e skk "Ryonkl-3, 4; 4, 6-di-O-neopropl; e: - g; -: “Namkcina B (in general, for: - ul -OS, H ,, xVCHCCHjJ -H). 13., g penta-H-ethoxycarbonylcanismine b, semi-genic, as indicated: Aa; M-; re, if dissolved in 70 ml, m; -; and even ROTEOp after the addition; g; K1cLS, & g 2, -dkg: eto; s: -shrops:; 1a and O, .55 g in a p-toluene-sulphate acid tank; find the tipH for 1 h, Obtained; 7i and rscHBOs are concentrated; - ib io to a 50-ml extractor and after dob; elvi 30 g 2 ,. 2-di. Metox: - prop; {and again inflate at 1 h. Add triethylamine and rast-cf you; shvayug to per & A mixed mixture of 500 ml of benzene and 500 MP of water, and a precipitate of solid A precipitates. After separation of the solid of Her substance A by filtration, the benzene residue is left to stand, the precipitate is filtered, washed with benzene and water, then dried to dryness. 3.5 g of solid are obtained, m.p. 23b-237 ° С, .З +87 (С-, з; I, dimethylformamide). , Obtained 8.1 g of solid protein A, gzl yugdegos penga-to-toxycarboicl-1-3 4; b-li-o-iso-propilideichavamycins Bf according to the same treatment that was written off by lice. Froze Synthesis of 2-0-beazoylpenta-N-ethoxycarbonyl-3, 4; 4, 6-di 0-isopropyl-5-tdencanamycin B (in the O6iuefj formula ..H,., X Y CHCCH,) .. 2 with c – 2 equals COqHj and Z with C 5 times H). 3.24 g of the kanamycin derivative B, para-, artificially 1-o, according to the procedure described in mayor 2, are dissolved in 48 ml of p; Ridnaou and 2 g of bensr-ichloride are added to the solution, the Rastaou is kept at the co;: 1 g temperatzer for 1 hour, then evaporated and the residue is dissolved in chloro. Ed. The solution npo / t ra..oT water, high -: K - .i,: is over sodium sulfate and concentrated to approximately 20 ml. When n-hexane is added, 3.35 g of crystals are formed, m.p. 205-209 0, 1, diketi formamide) Pr and m e r 4. Synthesis of 2-0 benzoyl. Ilpenta-M-ethoxycarbonyl-3, 4; 4 b-li-0-isopropylidecanamiaia B. 2.62 g of pre-treated kanamycin B, prepared according to the method described in Example 3, 3, are dissolved in 40 ml of water; ; acid acetic acid (1: 3) and a solution of H, - .npji 35 ° C 30 nkn. This raot1-O- package and 2.58 g of the resulting d; -a1.tonon1-; rovs nnsgo product solution to ti ii 5 i-wi d№ -. {Atl forms, ca. After the addition, 0.65 g of 2,2-dimethoxypropane and 55 mg of bioavailant p-toluenesul Phonic acid are kept at — room temperature for 1 hour. , 0, g insoluble 3 benzenes t. Substances, -ll. 285-267 C, + 105 ° C (C 1, dimethylformamil), YAN -spectrum (in dimethyl sulfoxide): g 9.72 to 8.60 (each 3-proton singlet is determined by the E value of the isolate-indidene ducts), 1 1.5 - 2, j (ton multiplet is determined for benzoyl runs). PRI me R 5. Synthesis of 2-0-benzoyl penta-N-ztoxycarbonyl-4 b-C-isopropylidec-3. 4-d / i-0-me; or nnamkcin (in general: 2k OC, Hj, V CHCCH, -), H / SOjCHj npK C - 2 is CO.H, and g at C - 5 is H) . 1.18 g of the kanamycin B derivative obtained as indicated in Example 4 was dissolved in 15 ml of pyridine and the solution after addition of C, 6 g of methylsulfonylchlorideCCH. SO. ce) stand at room temperature for 1.5 hours. The solution is concentrated to one third of the initial removal and the injection is poured. The precipitate that forms is filtered off and washed with Bsd. 1.32 g of solid are obtained, m.p. 198 ° C, ci. +107 (C 1.5, dimethylformamide G / NMR spectrum (in pyridine jr.dg: t 6.60 and 6.45 (each 3-proton singlet is determined for meelprotons) .JJ, P | P and me 6. Synthesis of 2-0 benzoyl 3, 4-dilessi-3, 47 dide hydropenta-H -e1oxycarbonyl-41 b-0-isopropyliden-β-amycin B. To a solution of 1.0 g of the kanamycin B derivative, obtained as indicated in Example 5, 11 g of sodium iodide and 5 zinc dust are added to 20 ml of dimethylformamide and the mixture is heated at 95 ° C for 1 h while stirring vigorously. Then the mixture is poured into a hot mixture of 100 ml of chloroform and 100 ml of water with stirring. The separated layer is separated, npoNbiBaraT is water, dried over sodium sulfate and evaporated to obtain 940 g of solid. The solid is treated with hot ethyl acetate and the remaining undissolved portion (340 m1) is recrystallized from a mixture of methanol, chloroform and ethyl acetate, mp 282-284 ° С, +36 (С i 0.4, dimethylformamide); NMR - spectrum, (from pyridine - d (2, O 6. (2-proton is an incompletely common singlet, Н - З and 4). J Example 7, Synthesis of 2-0 -benezo1 3, 4-dideoxypenta-N-ethoxycarbonyl-4. 6-0-isopropyl: -; Hanamits; 1na C A solution of 1.15 g of a derivative of kanamycy on B prepared as indicated in Example 6, B, a mixture of 45 t-ai p-lyoxane, 25 ml of methanol and 25, ml is hydrogenated under 2 atm in the presence of 0.3 g of platinum oxide, which was previously activated at room temperature for 5 hours. The resulting solution was filtered and evaporated, resulting in 1.1 G of a colorless powdery product, mp. 254-256 ° С, "467 (С - 0.2: ,, dimethylformamide) I; -: spectrum (in pyridine - dg: t 7, .8 - 8, i С4 - proton wide signal, H - 2, 4), Example 8. Synthesis of 2-0-be: Zoyl 3, 4-dideoxy-N-carboxyl-g-emicin B., 900 mg of the derivative of cane mimica and E, prepared as indicated in example 7, are dissolved in mixture 8 ml of acetic acid and 5 ml of water, after which the solution is heated at 100 C for 5 minutes. 750 ms of sediment is obtained, which is filtered and ayut is jumped out, so pl. 247-248 C + 3 +89 (C 2, 7, dimethylformamide); Found,%: C 52.41; H, 6.54; .W7.48, Calculated,%: C, 52.45; H6, 71 N7e .. b, o 9. Synthesis of 3, 4-dideo: Example of sycanamycin B. 150 mg of the kanamycin B derivative obtained as indicated in Example 8 and 2.3 g of barium hydroxide octahydrate hydrate are added to the mixture 5 ml of water and 4 ml of p-dioxane and the resulting mixture is heated in a bath of boiling water for 8 hours. Carbon dioxide is passed in and the precipitate is formed from a gas cylinder - centrifuged. The supernatant is separated and evaporated. The resulting residue is dissolved in water and the solution after filtration is chromatographed on a column filled with Amberlite 1TGS-50 ion exchange resin (. Form) using a 0.1-0.4 N. solution of ammonium oxide hydrate. Fraction, coz, ep Sl 3, 4-dideoxyxicanamycin B, concentrated. The addition of .acetone gives 47 mg of rustal dL ° +130 (C - 0.65, water). Found,% t C 47.71; H 8.38 N15,31 VUchisleno. %: from 47.68; H 8.26, N15.51. The invention The method of obtaining C, 4 - dilezohcancamycin B, is also distinguished by the fact that cagliolcin B is treated as usual. in a way that all amino groups and all hydroxyl groups are grouped, except for 3, 4-1 hydroxyl groups, s, 3, 4-hydroxyl groups are sulphated, the resulting derivative is processed in the usual way, removing 3, 4-D1: sulfoether groups, is reduced from 5, 3 that was formed, 4-unpowered flake ccezui with subsequent removal of the remaining SnOC7g TOVHfcst ggggashh gruggaglropok n tsezoy. aryl, er. hydroxy, arerecoxn or arnloproduct Bf4ue. HSBCCT-Hts i method. Prioritize by prPznakaTlg 29 .07 .70 - -zakptgul group dl.,. - group for . mon, -and .shog groups. nLnercn -5 Jf. .l. - SNP, -C01C, where R is hydrogen, olkpl, aralkyl,