56391-57-2

• 常用中文名：奈替米星硫酸盐
• 常用英文名：Netilmicin sulfate
• CAS号：56391-57-2
• 分子式：C₄₂H₉₂N₁₀O₃₄S₅
• 分子量：1441.6
• 相关类别： 原料药 抗生素类药物 氨基糖苷类药
• 发布时间：2018-02-04 08:00:00
• 更新时间：2026-07-05 20:05:22
• Netilmicin硫酸盐是氨基糖苷类抗生素化合物。

名称

• 中文名: 硫酸奈替米星
• 英文名: Netilmicin Sulfate
• 中文别名: Netilmicin Sulfate 硫酸奈替米星; 硫酸萘替米星USPEP; 1-N-乙基西索米星; 1- N-乙基西索米星; 硫酸奈替米星无菌微粉; 硫酸奈替米星NETILMICIN SULFATE; 硫酸萘替米星; 硫酸奈替米星/C1A; 硫酸奈替米星(标准品); 硫酸奈替米星 标准品; (2R,3R,4R,5R)-2-(((1S,2S,3R,4S,6R)-4-氨基-3-(((2S,3R)-3-氨基-6-(氨基甲基)-3,4-二氢-2H-吡喃-2-基)氧基)-6-(乙基氨基)-2-羟基环己基)氧基)-5-甲基-4-(甲基氨基)四氢-2H-吡喃-3,5-二醇 硫酸盐(2:5); 奈替米星杂质; Netilmicin sulfate (Standd)硫酸奈替米星 (Standd); 硫脲嘧啶; 硫酸奈替米星 27
• 英文别名: Netilmicin sulfate CRS; O-3-Deoxy-4-C-methyl-3-(methylamino)-β-L-abinopyranosyl-O-[2,6-diamino-2,3,4,6-tetradeoxy-a-D-glycero-hex-4-enopyranosyl-]-2-deoxy-N1-ethyl-D-strtamine sestersulfate; SCH-20569 (sulfate); Netilmicin sulfate for LC assay CRS/C1A; O-3-Deoxy-4-C-methyl-3-methylamino-ss-L-abinopyranosyl-(1-)-O-[2, 6-diamino-4,5-dehydro-2,3,4,6-tetradeoxy-a-D-glycero-hexopyranosyl-(1-)]-2-deoxy-1-N-ethyl-D-strtamine hemihtasulfate; Netromicine; Netilmicin sulfate salt; UNII-S741ZJS97U; sulfate(2:5)(salt); 1-N-ETHYLSISOMICIN SULFATE; certomycin; Netilmicin for peak identification CRS/C1A; EINECS 260-147-3; Netilmicin sulfate //BP; Netililn; NETILMICIN SULFATE SALT; O-3-Deoxy-4-C-methyl-3-(methylamino)-b-l-abinopyranosyl-O-[2,6-diamino-2,3,4,6-tetradeoxy-a-D-glycero-hex-4-enopyranosyl-]-2-deoxy-Nethyl-D-strtamine; (1S,2S,3R,4S,6R)-4-Amino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-6-(ethylamino)-2-hydroxycyclohexyl 3-deoxy-4-C-methyl-3-(methylamino)-β-L-arabinopyranoside sulfate (2:5); Nettacin; 1-N-Ethylsisomicin sulfate salt; Netilmicin Impurity; Netilmicin for peak identification; Netilimicin (sulfate); D-Strtamine, O-3-deoxy-4-C-methyl-3-(methylamino)-β-L-abinopyranosyl-(1→6)-O-[2,6-diamino-2,3,4,6-tetradeoxy-α-D-glycero-hex-4-enopyranosyl-(1→4)]-2-deoxy-N1-ethyl-, sulfate (2:5); 4-O-[[3α-Amino-6-(aminomethyl)-3,4-dihydro-2H-pyran]-2α-yl]-6-O-[4-C-methyl-3-(methylamino)-3-deoxy-β-L-abinopyranosyl]-N1-ethyl-2-deoxy-D-strtamine·2.5sulfuric acid; Netilmicin sulfhate; β-L-Arabinopyranoside, (1S,2S,3R,4S,6R)-4-amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl 3-deoxy-4-C-methyl-3-(methylamino)-, sulfate (2 :5) (salt); Netilmicin sulfate(2:5); NETILMYCIN SULPHATE; Netilmicin (sulfate); 1-N-ETHYLSISOMICIN; Zetamicin; MFCD01311715; O-3-Deoxy-4-C-Methyl-3-(MethylaMino)-β-l-abinopyranosyl-O-[2,6-diaMino-2,3,4,6-tetradeoxy-α-D-glycero-hex-4-enopyranosyl-]-2-deoxy-N'-ethyl-D-strtaMine; Natimicin sulfate; 6-diamino-2,3,4,6-tetradeoxy-alpha-d-glycero-hex-4-enopyranosyl-6)-o-(; NETILMYCIN SULFATE 27; Netilmicin sulfate salt,1-N-Ethylsisomicin; Naphthotidine sulfate; Netilmicin sulfate (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4-Amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-ethylamino-2-hydroxycyclohexyl]oxy-5-methyl-4-methylaminooxane-3,5-diol sulfate (2:5); Netilmicin Sulfate (SCH-20569); NETILMYCIN SULFATE; Netillin; Netilmicin Sulphate (NTC Sulphate), 595ug/mg; Netilmicin sulphate, 1-N-Ethylsisomicin; (2R,3R,4R,5R)-2-(((1S,2S,3R,4S,6R)-4-Amino-3-(((2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl)oxy)-6-(ethylamino)-2-hydroxycyclohexyl)oxy)-5-methyl-4-(methylamino)tetrahydro-2H-pyran-3,5-diol sulfate(2:5); (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4-amino-3-[[(2s,3r)-3-amino-6-(aminomethyl)-3,4-dihydro-2h-pyran-2-yl]oxy]-6-ethylamino-2-hydroxycyclohexyl]oxy-5-methyl-4-methylaminooxane-3,5-diol sulfate (2:5); First International Standd for Netilmicin; D-Strtamine, O-3-deoxy-4-C-methyl-3-(methylamino)-b-L-abinopyranosyl-(16)-O-[2,6-diamino-2,3,4,6-tetradeoxy-a-D-glycero-hex-4-enopyranosyl-]-2-deoxy-N1-ethyl-, sulfate (2:5) (salt) (9CI); Netromycin sulfate; Sulfate NetilMicin; O-3-DEOXY-4-C-METHYL-3-METHYLAMINO-BETA-L-ABINOPYRANOSYL-(1-)-O-[2, 6-DIAMINO-4,5-DEHYDRO-2,3,4,6-TETRADEOXY-A-D-GLYCERO-HEXOPYRANOSYL-(1-)]-2-DEOXY-1-N-ETHYL-D-STRTAMINE HEMIHTASULFATE; NETILMICIN SULFATE; netromycin; O-3-Deoxy-4-C-methyl-3-(methylamino)-l-abinopyranosyl-O-[2,6-diamino-2,3,4,6-tetradeoxy-a-D-glycero-hex-4-enopyranosyl-]-2-deoxy-N’-ethyl-D-strtamine

物化性质

• 密度: 1.32 g/cm3
• 沸点: 684.3ºC at 760 mmHg
• 熔点: >194ºC (dec.)
• 分子式: C₄₂H₉₂N₁₀O₃₄S₅
• 分子量: 1441.6
• 闪点: 367.7ºC
• 精确质量: 1440.4380959
• PSA: 814.36000
• LogP: 1.50400
• 外观性状: 白色至灰白色粉末
• 储存条件:

  密封、在2 ºC -8 ºC下保存

• 稳定性:

  如果遵照规格使用和储存则不会分解，未有已知危险反应

• 水溶解性: H2O: soluble10mg/mL | Soluble in water
• 计算化学:

  1、 疏水参数计算参考值（XlogP）：

  2、 氢键供体数量：26

  3、 氢键受体数量：44

  4、 可旋转化学键数量：16

  5、 互变异构体数量：

  6、 拓扑分子极性表面积（TPSA）：773

  7、 重原子数量：91

  8、 表面电荷：0

  9、 复杂度：754

  10、同位素原子数量：0

  11、确定原子立构中心数量：22

  12、不确定原子立构中心数量：0

  13、确定化学键立构中心数量：0

  14、不确定化学键立构中心数量：0

  15、共价键单元数量：7

• 更多:

  1. 性状：白色至淡黄色粉末

  2. 密度（g/mL,15ºC）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：未确定

  5. 沸点（ºC）：未确定

  6. 沸点（ºC，14mmHg）：未确定

  7. 折射率：未确定

  8. 闪点（°C）：未确定

  9. 比旋光度（ºC）：未确定

  10. 自燃点或引燃温度（ºC）： 未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：极易溶于水，几乎不溶于乙醇及乙醚。

生物活性

• 描述: Netilmicin硫酸盐是氨基糖苷类抗生素化合物。
• 相关类别:
  信号通路 >> 抗感染 >> 细菌
  研究领域 >> 感染
• 参考文献:

  [1]. Campoli-Richards DM, et al. Netilmicin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1989 Nov;38(5):703-56.

  [2]. Adams E, et al. Determination of netilmicin sulfate by liquid chromatography with pulsed electrochemical detection. J Chromatogr A. 1998 Jul 3;812(1-2):151-7.

  [3]. Ciftci M, et al. Effects of some drugs on rat erythrocyte 6-phosphogluconate dehydrogenase: an in vitro and in vivo study. Pol J Pharmacol. 2002 May-Jun;54(3):275-80.

毒性和生态

毒理学数据: LD50(mg/kg)小鼠：静脉注射40，腹腔注射125，皮下注射175[1.19] 生态学数据: 对水是稍微有危害的不要让未稀释或大量的产品接触地下水、水道或者污水系统，若无政府许可，勿将材料排入周围环境。 CHEMICAL IDENTIFICATION RTECS NUMBER : WK2286000 CAS REGISTRY NUMBER : 56391-57-2 LAST UPDATED : 199604 DATA ITEMS CITED : 17 MOLECULAR FORMULA : C21-H41-N5-O7.5/2H2-O4-S MOLECULAR WEIGHT : 720.80 WISWESSER LINE NOTATION : T6O BUTJ B1Z EZ FO- BL6TJ AZ CQ EM2 DO- BT6OTJ CQ DM1 EQ E1 ..H2.S-O4 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,1249,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 231 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 169 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 40700 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 167 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 189 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) REFERENCE : AMACCQ Antimicrobial Agents and Chemotherapy. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1972- Volume(issue)/page/year: 10,827,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 68900 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 22 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 63100 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 420 mg/kg/14D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 375 mg/kg/30D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes in urine composition Kidney, Ureter, Bladder - changes in bladder weight REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,461,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1365 mg/kg/26W-I TOXIC EFFECTS : Kidney, Ureter, Bladder - interstitial nephritis Kidney, Ureter, Bladder - changes in bladder weight Blood - pigmented or nucleated red blood cells REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,499,1982 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 138 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - physical REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,614,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 550 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,614,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 650 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,643,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 455 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,659,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4347 No. of Facilities: 25 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 2440 (estimated) No. of Female Employees: 1459 (estimated)

安全

• 符号: GHS07, GHS08
• 信号词: Danger
• 危害声明: H312 + H332-H360
• 警示性声明: P201-P261-P280-P308 + P313
• 个人防护装备: Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
• 危害码 (欧洲): T:Toxic;
• 风险声明 (欧洲): R60;R20/21/22
• 安全声明 (欧洲): S53-S36/37/39-S45
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: WK2286000
• 海关编码: 2942000000

制备

参考文献[12~15]推荐如下路线和方法$

(1)3,2’,6’-三（N-乙酰）西索米星（023-2）的制备

在反应瓶中加入二甲基甲酰胺（DMF）/水的混合溶液100ml(DMF/水,体积比6:2)和乙酸铜5.5g(0.03mol),搅拌悬浮,再加入西索米星(023-1)4.5g(0.01mol),搅拌下加三乙胺调至PH8.5~10.5,在搅拌30min后降温至5 ºC 慢慢滴加乙酸酐3.1g(0.03mol)的3.5mlDMF溶液,滴加时控温在0~10 ºC ,在强烈搅拌下,并不断用三乙胺调节反应液的PH保持8.5~10.5,滴毕,室温(25 ºC)搅拌反应30min~1h.用TLC跟踪显示反应达终点后(如果未达到终点应补乙酸酐的DMF溶液适量),将反应液减压下浓缩,浓缩液用水稀释,冷至(0~10 ºC )保持4h.过滤去固体,滤液用阳离子交换树脂处理,氨水洗脱等处理后得023-2 5.2g,收率90%.

(2)5,2’’,4’’-三(三甲基硅)-3,2’,6’-三(N-乙酰)-西索米星(023-3)的制备

在反应瓶中加入023-2 10g(17.45mmol)、1,2-二甲氧基乙烷(DMF)100ml,搅拌溶解,再加入三甲基氯硅烷25ml(21.15g,194mmol),加热至50 ºC ,搅拌反应16h(在保持50~55 ºC 下)减压蒸除DME,得黄色固体023-3 13.5g,收率93.6%左右,含量91%.经硅胶柱色谱纯化可制得分析试样.

(3)5,2’’,4’’-三(三甲基硅)-1-乙基氨基-3,2’,6’-三(N-乙酰)西索米星(023-5)的制备

在反应瓶中加入化合物023-3 8g(9.5mmol)和水80ml,搅拌溶解,用4mol/L盐酸调至PH6.降温至15 ºC ,加入乙醛2.2ml(1.72g,39mmol),搅拌反应30min,生成亚胺化合物023-4溶液.将NaBH4的水溶液5ml[1g(26.47mmol)NaBH4溶于5ml水]匀速滴入上述含023-4的溶液，并用0.5mol/L盐酸严格控制PH6.继续反应30min,加入0.05mol/L硼砂溶液20ml(PH9.5)继续搅拌1h.得023-5的溶液,含量85%,备用.

(4)O-3-脱氧-4-C-甲基-3-(甲氨基)-B-L-阿拉伯吡喃糖苷(1—6)-O-[2,6-二氨基-2,3,4,6-四脱氧-a-D-甘油己糖-4-烯醇型吡喃糖苷基-(1—4)]-2-脱氧-N’-乙基-D-链霉胺硫酸盐(硫酸奈替米星)(023)的合成

在反应瓶中加入上步制备的含化合物023-5的溶液、珠粒状固体NaOH2g(50mmol)和Na2CO3 2.7g(25.5mmol),搅拌溶解,油浴加热升温至110 ºC ,在该温度下搅拌回流36h.降温至10~15 ºC,加入10mol/L H2SO4调反应液PH至6.5~7.0,抽滤,滤液即为奈替米星游离碱的澄清溶液,含量80%.

在上述澄清溶液中加入阳离子交换树脂,搅拌混合充分后,过滤,用7%氨水洗脱,洗脱液浓缩后用甲醇溶解,再上硅胶柱色谱分离纯化,用氯仿/甲醇/水(40:20:7)洗脱分离.将洗脱液减压浓缩至约10ml,加入活性炭0.5g,恒温水浴加热至50 ºC ,脱色30min.抽滤,滤液用10mol/L H2SO4调至PH3.5~5.5,匀速滴至无水乙醇300ml中,3h后抽滤,滤饼干燥,得023 5.93g,收率78.7,含量在97%以上,符合《中国药典》(2005年版)质量标准.该品为非结晶性固体(冷冻干燥).

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