6'-N-benzyloxycarbonylneamine | 77967-96-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6'-N-benzyloxycarbonylneamine
• 英文别名: 6'-N-carbobenzyloxyneamine
• CAS: 77967-96-5
• 化学式: C₂₀H₃₂N₄O₈
• 分子量: 456.496
• InChiKey: ZBLRBJIUXCFUSE-ITRADPEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.15
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  215.77
• 氢给体数：
  8.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  6'-N-benzyloxycarbonylneamine 在 palladium on activated charcoal 吡啶 、 氢气 、 六甲基二硅氮烷 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Conjoint molecules of cephalosporins and aminoglycosides

  摘要：

  A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial beta -lactamases, enzymes that hydrolyze the beta -lactam bond of cephalosporins. Hydrolysis of the beta -lactam bond was expected to release the Clo-appended aminoglycoside. Since beta -lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.

  DOI：

  10.1002/1521-4184(200109)334:8/9<295::aid-ardp295>3.0.co;2-3
• 作为产物：
  描述：

  neamine tetrahydrochloride 、 N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide 在 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.25h， 生成 6'-N-benzyloxycarbonylneamine
  参考文献：
  名称：

  Conjoint molecules of cephalosporins and aminoglycosides

  摘要：

  A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial beta -lactamases, enzymes that hydrolyze the beta -lactam bond of cephalosporins. Hydrolysis of the beta -lactam bond was expected to release the Clo-appended aminoglycoside. Since beta -lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.

  DOI：

  10.1002/1521-4184(200109)334:8/9<295::aid-ardp295>3.0.co;2-3

文献信息

• Total Synthesis of Aminoglycoside Antibiotics, Apramycin and Saccharocin (KA-5685)
  作者：Kuniaki Tatsuta、Kohji Akimoto、Hideaki Takahashi、Takao Hamatsu、Masahiko Annaka、Mitsuhiro Kinoshita

  DOI：10.1246/bcsj.57.529

  日期：1984.2

  Apramycin and saccharocin (KA-5685) have been synthesized from previously synthesized neamine (3). Addition of allylmagnesium chloride to 4-O-[3′,4′-O-cyclohexylidene-2′-deoxy-2′-(tosylamino)-α-d-gluco-hexodialdo-1′,5′-pyranosyl]-5,6-O-cyclohexylidene-1,3-di-N-tosyl-2-deoxystreptamine which was derived from 3 through the 6′-N-oxide, gave 4-O-[3′,4′-O-cyclohexylidene-2′,7′,8′,9′-tetradeoxy-2′-(tosylamino)-l-glycero- and d-glycero-α-d-gluco-non-8′-enopyranosyl]-5,6-O-cyclohexylidene-1,3-di-N-tosyl-2-deoxystreptamines which were in turn converted into 4-O-[(8′S)-7′-N,6′-O-carbonyl-2′,3′,7′-trideoxy-8′-O-methyl-7′-(methylamino)-2′-(tosylamino)-d-glycero-α-d-allo-octodialdo-1′,5′:8′,4′-dipyranos-1′-yl]-5,6-O-cyclohexylidene-1,3-di-N-tosyl-2-deoxystreptamine (25), via azidonitration of 1-N-acetyl-4-O-[3′,6′-di-O-acetyl-4′,8′-anhydro-2′,7′-dideoxy-2′-(tosylamino)-l-glycero-α-d-gluco-oct-7′-enopyranos-1′-yl]-5,6-O-cyclohexylidene-1,3-di-N-tosyl-2-deoxystreptamine and epimerization of the 6′-hydroxyl group. Successive deprotection of 25 afforded aprosamine, from which 1,2′,3,7′-tetrakis(N-benzyloxycarbonyl)aprosamine (28) was prepared, and glycosidation of 28 with 4-azido-2,3,6-tri-O-benzyl-4-deoxy-β-d-glucopyranosyl fluoride or 2,3,4,6-tetra-O-benzyl-β-d-glucopyranosyl fluoride, followed by hydrogenolysis, completed the total synthesis.

  阿普拉霉素和蔗糖霉素（KA-5685）已从先前合成的尼阿霉素（3）合成。将烯丙基氯化镁添加到4-O-[3′，4′-O-环己叉-2′-脱氧-2′-（对甲苯磺酰氨基）-α-d-葡六双醛-1′，5′-吡喃糖基]-5，6-O-环己叉-1，3-二-N-对甲苯磺酰-2-脱氧链霉胺（由3通过6′-N-氧化物衍生得到），得到4-O-[3′，4′-O-环己叉-2′，7′，8′，9′-四脱氧-2′-（对甲苯磺酰氨基）-l-甘油和d-甘油-α-d-葡-8′-烯吡喃糖基]-5，6-O-环己叉-1，3-二-N-对甲苯磺酰-2-脱氧链霉胺，后者又转化为4-O-[（8′S）-7′-N，6′-O-羰基-2′，3′，7′-三脱氧-8′-O-甲基-7′-（甲氨基）-2′-（对甲苯磺酰氨基）-d-甘油-α-d-别辛双醛-1′，5′：8′，4′-双吡喃糖基]-5，6-O-环己叉-1，3-二-N-对甲苯磺酰-2-脱氧链霉胺（25），通过1-N-乙酰基-4-O-[3′，6′-二-O-乙酰基-4′，8′-无水-2′，7′-二脱氧-2′-（对甲苯磺酰氨基）-l-甘油-α-d-葡-7′-烯吡喃糖基]-5，6-O-环己叉-1，3-二-N-对甲苯磺酰-2-脱氧链霉胺的叠氮化硝化和6′-羟基的差向异构化。25的连续脱保护得到阿普拉霉素，从中制备了1，2′，3，7′-四（N-苄氧羰基）阿普拉霉素（28），以及28与4-叠氮-2，3，6-三-O-苄基-4-脱氧-β-d-吡喃葡糖基氟或2，3，4，6-四-O-苄基-β-d-吡喃葡糖基氟的糖基化，随后进行氢解，完成了全合成。
• Synthesis and use of sulfonamide-, sulfoxide-, or sulfone-containing aminoglycoside–CoA bisubstrates as mechanistic probes for aminoglycoside N-6′-acetyltransferase
  作者：Feng Gao、Xuxu Yan、Omar Zahr、Aaron Larsen、Kenward Vong、Karine Auclair

  DOI：10.1016/j.bmcl.2008.09.004

  日期：2008.10

  Aminoglycoside-coenzyme A conjugates are challenging synthetic targets because of the wealth of functional groups and high polarity of the starting materials. We previously reported a one-pot synthesis of amide-linked aminoglycoside-CoA bisubstrates. These molecules are nanomolar inhibitors of aminoglycoside N-6'-acetyltransferase Ii (AAC(6')-Ii), an important enzyme involved in bacterial resistance

  氨基糖苷-辅酶A共轭物因具有丰富的官能团和起始原料的高极性而成为具有挑战性的合成靶标。我们以前报道过一锅法合成酰胺连接的氨基糖苷-CoA双底物。这些分子是氨基糖苷N-6'-乙酰基转移酶Ii（AAC（6'）-Ii）的纳摩尔抑制剂，这是一种对细菌对氨基糖苷抗生素具有抗性的重要酶。我们在这里报告了五个新的包含磺酰胺，亚砜或砜基团的氨基糖苷-CoA双底物的合成和生物活性。有趣的是，与酰胺连接的双底物相比，预期最能模仿四面体中间体的磺酰胺连接的双底物没有显示出改善的抑制作用。另一方面，