5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconolactam | 272123-95-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconolactam
• 英文别名: 2,3,4-tri-O-benzyl-D-glucono-δ-lactam；(3R,4R,5R,6R)-3-hydroxy-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)piperidin-2-one
• CAS: 272123-95-2
• 化学式: C₂₇H₂₉NO₅
• 分子量: 447.531
• InChiKey: CSCKAJMRORDKGG-VEYUFSJPSA-N

物化性质

• 沸点：
  644.3±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconolactam 在 盐酸 、 lithium aluminium tetrahydride 、 草酰氯 、 palladium on carbon 、 氢气 、 L-Selectride 、 potassium carbonate 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 36.5h， 生成 1-甘露糖野尻霉素盐酸盐
  参考文献：
  名称：

  1-Deoxymannojirimycin的便捷克级合成

  摘要：

  摘要 1-去氧麦诺吉利霉素的从四-一种新的克级合成ö苄基d报道-glucopyranose在9个步骤并用的纯化步骤数量有限的28％的总收率。合成策略是基于在四区域选择性脱保护和OH基团的结构的随后的反转在C-2 ö苄基d -glucono-δ内酰胺，朝向1-脱氧野尻霉素衍生物的合成也是一个高级中间体。 1-去氧麦诺吉利霉素的从四-一种新的克级合成ö苄基d报道-glucopyranose在9个步骤并用的纯化步骤数量有限的28％的总收率。合成策略是基于在四区域选择性脱保护和OH基团的结构的随后的反转在C-2 ö苄基d -glucono-δ内酰胺，朝向1-脱氧野尻霉素衍生物的合成也是一个高级中间体。

  DOI：

  10.1055/s-0035-1561323
• 作为产物：
  描述：

  (3R,4S,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)-2-piperidinone 在 四丁基溴化铵 、 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 生成 5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconolactam
  参考文献：
  名称：

  利用2-氧代-C-烯丙基亚氨基糖，构象锁定的DNJ和DMJ衍生物的合成和糖苷酶抑制。

  摘要：

  制备了亚氨基糖1-脱氧野oji霉素（DNJ）和1-脱氧甘露菌霉素（DMJ）的一系列类似物，其中将额外的五或六元环与C1-C2键稠合。该合成策略利用了关键的2-酮-C-烯丙基亚氨基糖，该糖可容易地从葡糖酸内酰胺获得，在格利雅（Grignard）添加和RCM的作用下，该双环可提供双环骨架，该骨架可在C [双键]处进一步羟基化，长度为m-C 。该策略为DNJ模拟提供了哌啶环与六元环稠合时锁定在1C4构象的方式，所有取代基均沿轴向定向。已证明在DNJ和DMJ基序上增加一个额外的环会强烈修饰亲本亚氨基糖的糖苷酶抑制谱，从而产生适度的抑制剂。

  DOI：

  10.1039/c9ob01402k

文献信息

• Metal-Free Iodine-Mediated Deoxygenation of Alcohols in the Position α to Electron-Withdrawing Groups
  作者：Maëva M. Pichon、Fabien Stauffert、Luis G. Addante-Moya、Anne Bodlenner、Philippe Compain

  DOI：10.1002/ejoc.201800051

  日期：2018.4.9

  The use of a substoichiometric amount of molecular iodine in the presence of PPh3 and pyridine effects a direct deoxygenation of primary and secondary alcohols in positions α to a variety of activating electron‐withdrawing groups, including ketones, esters, amides, imides and nitrile groups.

  在 PPh3 和吡啶的存在下，使用亚化学计量的分子碘可将 α 位的伯醇和仲醇直接脱氧为各种活化的吸电子基团，包括酮、酯、酰胺、酰亚胺和腈基。
• Synthesis and evaluation of two mannosamine-derived lactone-type inhibitors of snail β-mannosidase
  作者：Miroslav Terinek、Andrea Vasella

  DOI：10.1016/j.tetasy.2004.11.068

  日期：2005.1

  The inhibition of snail beta-mannosidase by the manno-configured amino- and hydroxy-lactams and -imidazoles 7-10 was compared to the inhibition of the beta-glucosidases from Caldocellum saccharolyticum and from sweet almonds by the gluco-configured amino- and hydroxy-lactams and -imidazoles 1, 2, 5 and 6 [DeltaDeltaG(diss)(OH --> NH3+)]- Substitution in the gluco-configured 1, 3 and 5, of C(2)-OH by an ammonium group strengthens the interaction of the inhibitor with the catalytic nucleophile of retaining beta-glucosidases, and weakens the interaction with the catalytic acid. The analogous substitution in the manno-configured inhibitors 7 and 9, leading to 8 and 10, respectively, was expected to only reflect the impaired interaction of the inhibitor with the catalytic acid, as the catalytic nucleophile and the C(2) substitueut are located on opposite sides of the average ring plane.The mannonolactam 10 was synthesized from the known hydroxy-lactam 11 by O-mesylation followed by azidation and hydrogenation. Sultone 13 was formed as side product upon mesylation of 11. The imidazole 8 was obtained from 11, similarly to the synthesis of the known gluco-isomer 2, via the hydroxy-imidazoles 22 and 23; best results were obtained by protecting 11 as the triisopropylsilyl ether 29.The resulting inhibition by the imidazoles 7 and 8 was interpreted as reflecting an improved binding of the catalytic nucleophile of snail P-mannosidase with the protonated imidazolc ring of 8 and an impaired interaction with the catalytic acid, while a comparison of the inhibition by the lactams 9 and 10 is in keeping with the results that are expected if there is no significant interaction between the catalytic nucleophile of snail beta-mannosidase and the C(2)-OH group of beta-mannosides. The amino-imidazole 8 is a surprisingly strong inhibitor of the a-mannosidase from Jack beans [K-i = 1.22 muM; mixed-type (alpha = 2.3)]. (C) 2004 Elsevier Ltd. All rights reserved.
• ——
  作者：Narendra Panday、Muthuppalaniappan Meyyappan、Andrea Vasella

  DOI：10.1002/(sici)1522-2675(20000315)83:3<513::aid-hlca513>3.0.co;2-1

  日期：2000.3.15

  The inhibition of the beta-glucosidases from sweet almonds and Caldocellum saccharolyticum at varying pH values by the glucosamine-related inhibitors 1-7 has been compared to the inhibition by the known glucose analogues 8-14. The amino derivatives 3, 4, 6, and 7 were prepared in one step from the known 15-18 (Scheme I), and the amino-1,2,3-triazole 5 by a variant of the synthesis leading to the glucose analogue 12 (Scheme 2). The key step Tor the preparation of the aminoimidazole 1 and of the amino-1,2,4-triazole 2 is the regioselective cleavage of the benzyloxy group at C(2) of the gluconolactam 35 and the mannonolactam 57 respectively, by BCl3 and B4NBr (Schemes 3 and 4, resp.). The pH optimum for the inhibition by the amines is lower than their pK(HA) values, evidencing that they are bound as ammonium salts and that H-bonding between C(2)-NH3+ and the cat. base B- contributes more strongly to binding than any possible H-bond to the NH2-C(2) group. The influence of the ammonium group on the inhibitory strength correlates with the basicity of the 'glycosidic heteroatom'. The strongest increase of the inhibitory strength is observed for the amines lacking a 'glycosidic heteroatom' (Delta Delta G(OH-->NH3+)=-1.5 to -2.9 kcal/mol). The increase is less; derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' pronounced for the amino derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' (Delta Delta G(OH --> NH3+) = - 0.6 to - 1.1 kcal/mol); the amino compounds 1 and 2, which possess a strongly basic 'glycosidic heteroatom', are weaker inhibitors than the corresponding hydroxy compounds, as expressed by Delta Delta G(OH-->NH3+) between +4.3 and +4.7 kcal/mol for the amino-imidazole 1, and between +2.3 and 2.8 kcal/mol for the amino-1,2,4-triazole 2, denoting the dominant detrimental influence of a C(2) -NH3+ group on the H-bond acceptor properties of a sufficiently basic 'glycosidic heteroatom'.
• A Convenient, Gram-Scale Synthesis of 1-Deoxymannojirimycin
  作者：Philippe Compain、Fabien Stauffert、Mathieu Lepage、Maëva Pichon、Damien Hazelard、Anne Bodlenner

  DOI：10.1055/s-0035-1561323

  日期：——

  gram-scale synthesis of 1-deoxymannojirimycin from tetra-O-benzyl-d-glucopyranose in 9 steps and 28% overall yield with a limited number of purification steps is reported. The synthetic strategy is based on the regioselective deprotection and subsequent inversion of configuration of the OH group at C-2 in tetra-O-benzyl-d-glucono-δ-lactam, also an advanced intermediate toward the synthesis of 1-deoxynojirimycin

  摘要 1-去氧麦诺吉利霉素的从四-一种新的克级合成ö苄基d报道-glucopyranose在9个步骤并用的纯化步骤数量有限的28％的总收率。合成策略是基于在四区域选择性脱保护和OH基团的结构的随后的反转在C-2 ö苄基d -glucono-δ内酰胺，朝向1-脱氧野尻霉素衍生物的合成也是一个高级中间体。 1-去氧麦诺吉利霉素的从四-一种新的克级合成ö苄基d报道-glucopyranose在9个步骤并用的纯化步骤数量有限的28％的总收率。合成策略是基于在四区域选择性脱保护和OH基团的结构的随后的反转在C-2 ö苄基d -glucono-δ内酰胺，朝向1-脱氧野尻霉素衍生物的合成也是一个高级中间体。
• Synthesis and glycosidase inhibition of conformationally locked DNJ and DMJ derivatives exploiting a 2-oxo-<i>C</i>-allyl iminosugar
  作者：Quentin Foucart、Yuna Shimadate、Jérôme Marrot、Atsushi Kato、Jérôme Désiré、Yves Blériot

  DOI：10.1039/c9ob01402k

  日期：——

  or six-membered ring has been fused to the C1-C2 bond have been prepared. The synthetic strategy exploits a key 2-keto-C-allyl iminosugar, easily accessible from gluconolactam, which upon Grignard addition and RCM furnishes a bicyclic scaffold that can be further hydroxylated at the C[double bond, length as m-dash]C bond. This strategy furnished DNJ mimics with the piperidine ring locked in a 1C4 conformation

  制备了亚氨基糖1-脱氧野oji霉素（DNJ）和1-脱氧甘露菌霉素（DMJ）的一系列类似物，其中将额外的五或六元环与C1-C2键稠合。该合成策略利用了关键的2-酮-C-烯丙基亚氨基糖，该糖可容易地从葡糖酸内酰胺获得，在格利雅（Grignard）添加和RCM的作用下，该双环可提供双环骨架，该骨架可在C [双键]处进一步羟基化，长度为m-C 。该策略为DNJ模拟提供了哌啶环与六元环稠合时锁定在1C4构象的方式，所有取代基均沿轴向定向。已证明在DNJ和DMJ基序上增加一个额外的环会强烈修饰亲本亚氨基糖的糖苷酶抑制谱，从而产生适度的抑制剂。