(3S,4R)-N-benzyloxycarbonyl-3,4-dihydroxy-6-(amino)hexan-2-one | 1000855-21-9

• 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: (3S,4R)-N-benzyloxycarbonyl-3,4-dihydroxy-6-(amino)hexan-2-one
• 英文别名: benzyl ((3R,4S)-3,4-dihydroxy-5-oxohexyl)carbamate；benzyl N-[(3R,4S)-3,4-dihydroxy-5-oxohexyl]carbamate
• CAS: 1000855-21-9
• 化学式: C₁₄H₁₉NO₅
• 分子量: 281.309
• InChiKey: KCMNENOJQFIXKF-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R)-N-benzyloxycarbonyl-3,4-dihydroxy-6-(amino)hexan-2-one 在 palladium dihydroxide 氢气 、 二乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、2.76 MPa 条件下， 生成 (2R,3R,4R)-2-methylpiperidine-3,4-diol
  参考文献：
  名称：

  d-Fructose-6-Phosphate Aldolase-Catalyzed One-Pot Synthesis of Iminocyclitols

  摘要：

  A one-pot chemoenzymatic method for the synthesis of a variety of new iminocyclitols from readily available, non-phosphorylated donor substrates has been developed. The method utilizes the recently discovered fructose-6-phosphate aldolase (FSA), which is functionally distinct from known aldolases in its tolerance of different donor substrates as well as acceptor substrates. Kinetic studies were performed with dihydroxyacetone (DHA), the presumed endogenous substrate for FSA, as well as hydroxy acetone (HA) and 1-hydroxy-2-butanone (HB) as donor substrates, in each case using glyceraidehyde-3-phosphate as acceptor substrate. Remarkably, FSA used the three donor substrates with equal efficiency, with k(cat)/K-M-values of 33, 75, and 20 M-1 s(-1), respectively. This level of donor substrate tolerance is unprecedented for an aldolase. Furthermore, DHA, HA, and HB were accepted as donors in FSA-catalyzed aldol reactions with a variety of azido- and Cbz-amino aldehyde acceptors. The broad substrate tolerance of FSA and the ability to circumvent the need for phosphorylated substrates allowed for one-pot synthesis of a number of known and novel iminocyclitols in good yields, and in a very concise fashion. New iminocyclitols were assayed as inhibitors against a panel of glycosidases. Compounds 15 and 16 were specific alpha-mannosidase inhibitors, and 24 and 26 were potent and selective inhibitors of beta-N-acetylglucosaminidases in the submicromolar range. Facile access to these compounds makes them attractive core structures for further inhibitor optimization.

  DOI：

  10.1021/ja073911i
• 作为产物：
  描述：

  N-苄氧羰基-3-氨基丙醛 、 羟基丙酮 在 1,4-二巯基-2,3-丁二醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以96%的产率得到(3S,4R)-N-benzyloxycarbonyl-3,4-dihydroxy-6-(amino)hexan-2-one
  参考文献：
  名称：

  Structure-guided redesign of d-fructose-6-phosphate aldolase from E. coli: remarkable activity and selectivity towards acceptor substrates by two-point mutation

  摘要：

  通过重新设计大肠杆菌 D-果糖-6-磷酸醛缩酶的受体结合位点，构建了 FSA A129S/A165G 双突变体，其对 N-苄氧羰基氨基醛衍生物的活性比野生型高出 5 到 900 倍。

  DOI：

  10.1039/c1cc11069a

文献信息

• Biocatalytic Transamination of Aldolase‐Derived 3‐Hydroxy Ketones
  作者：Mathias Pickl、Markus Ebner、Samantha Gittings、Pere Clapés、Wolfgang Kroutil

  DOI：10.1002/adsc.202300201

  日期：2023.5.12

  furnishing enantioenriched 1,3-amino alcohols out of commodity chemicals. A Type I aldolase forged the carbon backbone with an enantioenriched aldol motif, which was subsequently subjected to enzymatic transamination. A panel of 194 TAs was tested on diverse nine aldol products prepared through different nucleophiles and electrophiles. Due to the availability of (R)- and (S)-selective TAs, both diastereomers

  尽管光学纯氨基醇因其广泛的适用性而需求量很大，但由于需要通常详细的保护策略，因此它们的合成仍然具有挑战性。在这里，提出了一种多酶方法，该方法绕过了这一障碍，从商品化学品中提供富含对映体的 1,3-氨基醇。I 型醛缩酶用对映体富集的羟醛基序形成碳骨架，随后进行酶促转氨化。一组 194 种 TA 在通过不同亲核试剂和亲电试剂制备的不同 9 种羟醛产品上进行了测试。由于 （R） 和 （S） 选择性 TA 的可用性，1,3-氨基醇基序的两种非对映异构体都是可及的。两步法工艺能够合成所需的氨基醇，最终产品中具有多达三个手性中心，de 高达 >97。