(2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine | 340970-04-9

• 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: (2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine
• 英文别名: benzyl (2R,3R,4R,5S)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-5-(hydroxymethyl)-3,4-bis(phenylmethoxy)pyrrolidine-1-carboxylate
• CAS: 340970-04-9
• 化学式: C₄₄H₄₉NO₆Si
• 分子量: 715.962
• InChiKey: HQTJZKBOCDLIQL-CVGILMMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.12
• 重原子数：
  52
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine 在 4-二甲氨基吡啶 、 四丙基高钌酸铵 、 四丁基氟化铵 、 N-甲基吗啉氧化物 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 benzyl (2S,3R,4R,5S)-2-(benzoyloxymethyl)-5-formyl-3,4-bis(phenylmethoxy)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Polyhydroxylated pyrrolizidines. Part 4: Total asymmetric synthesis of unnatural hyacinthacines from a protected derivative of DGDP

  摘要：

  (1R,2R,3S,5R,7aR)-1,2-二羟基-3-(羟甲基)-5-甲基吡咯烷二酮 [(+)-3-表海葱素 A(3)] 1 和 (1R,2R,3S,7aR)-1,2-二羟基-3-(羟甲基)吡咯烷二酮 [(+)-3-表海葱素 A(2)] 2 是通过 Wittig 方法[1](使用由 (2R,3R,4R,5S)-3,4-二苯氧基-N-苯氧羰基-2'-O-(特丁基二苯基)硅基-2,5-双(羟甲基)吡咯烷[2]（部分保护的 DGDP）制备的醛 6 以及相应的亚甲基, 然后分别通过 α,β-不饱和酮 7 和醛 8 的内源性还原胺化步骤进行环化, 最后完成完全脱保护而合成的。 (C) 2004 Elsevier Ltd. 保留所有权利。 [1] Wittig 方法：一种用于构建碳-碳双键的化学反应方法，通常涉及将醛或酮与 Wittig 试剂（如亚甲基化合物）反应生成烯烃。 [2] DGDP：二羟基-PDOT（双(羟甲基)吡咯烷)的缩写形式。

  DOI：

  10.1016/j.tetasy.2004.03.013
• 作为产物：
  描述：

  10-(benzyloxy)-2,2-dimethyl-1,3,6-trioxaspiro(4,5)decane-8,9-diol 在 镍 咪唑 、 sodium azide 、 氢气 、 二正丁基氧化锡 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~110.0 ℃ 、345.0 kPa 条件下， 反应 119.0h， 生成 (2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine
  参考文献：
  名称：

  A practical route to partially protected pyrrolidines as precursors for the stereoselective synthesis of alexines

  摘要：

  Either 3-O-benzoyl- (2a) or 3-O-benzyl-1,2-O-isopropylidene-beta-D-fructopyranose (2b) were regioselectively O-benzylated at C-4 to give 4a and 4b, respectively, which were transformed into 5-azido-3-O-benzoyl-4-O-benzyl- (6a) and 5-azido-3,4-di-O-benzyl-5-deoxy-1,2-O-isopropylidene-alpha-L-sorbopyranose (6b) by nucleophilic displacement of the corresponding 5-O-mesyl derivatives 5a and 5b by sodium azide in DMF, respectively. Compound 6b was also prepared from 4b in one step by the Mitsunobu methodology. Deacetonation of 6a and 6b gave the partially protected free azidouloses 8a and 8b, respectively, that were protected as their 1-O-TBDPS derivatives 9a and 9b. Hydrogenation of 9b over Raney nickel gave stereoselectively (2R,3R,4R,5S)-3,4-dibenzyloxy-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine (12) which was identified by transformation into the well known (2R,3R,4R,5S)-3,4-dihydroxy-2,5-bis(hydroxymethyl)pyrrolidine (1, DGDP).

  DOI：

  10.1016/s0008-6215(00)00319-0

文献信息

• Polyhydroxylated Pyrrolidines: Synthesis of Trideoxy-2,5-iminohexitols
  作者：Isidoro Izquierdo、María Plaza、Juan Tamayo、Daniele Lo Re、Fernando Sánchez-Cantalejo

  DOI：10.1055/s-2008-1072566

  日期：2008.5

  A series of naturally occurring pyrrolidine alkaloids and analogues, with the general structure of trideoxy-2,5-iminohexitols (imino- or azasugars), have been enantiosynthesized using triorthogonally protected pyrrolidines, previously prepared from commercial d-fructose, as homochiral starting materials. The inhibitory activity of some of the described compounds against glycosidases and glycosyltransferases makes them potential therapeutic agents.

  利用以前从商用 d-果糖中制备的三正对映体保护的吡咯烷作为同手性起始原料，合成了一系列天然存在的吡咯烷生物碱和类似物，其一般结构为三脱氧-2,5-亚氨基己糖醇（亚氨基或氮杂杉糖）。其中一些化合物对糖苷酶和糖基转移酶具有抑制活性，因此具有潜在的治疗作用。
• Polyhydroxylated pyrrolizidines. Part I: Short and highly stereocontrolled syntheses of hyacinthacines
  作者：Isidoro Izquierdo、Marı́a T. Plaza、Rafael Robles、Francisco Franco

  DOI：10.1016/s0957-4166(01)00440-2

  日期：2001.9

  Two short and highly stereocontrolled syntheses for 7a-epi-hyacinthacine A(2) (7-deoxyalexine) 3 and 5,7a-diepihyacinthacine A(3) 4 are, respectively, reported herein. An appropriately protected polyhydroxypyrrolidine. (2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine 5, readily available from D-fructose, was chosen as the chiral starting material. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Polyhydroxylated pyrrolizidines. Part 4: Total asymmetric synthesis of unnatural hyacinthacines from a protected derivative of DGDP
  作者：Isidoro Izquierdo、Marı́a T Plaza、Francisco Franco

  DOI：10.1016/j.tetasy.2004.03.013

  日期：2004.5

  (1R,2R,3S,5R,7aR)-1,2-Dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-3-epi-hyacinthacine A(3)] 1 and (1R,2R,3S,7aR)-1,2-dihydroxy-3-hydroxymethylpyrrolizidine [(+)-3-epi-hyacinthacine A(2)] 2 have been synthesized by Wittig's methodology using aldehyde 6, prepared from (2R,3R,4R,5S)-3,4-dibenzyloxy-N-benzyloxycarbonyl-2'-O-tent-butyldiphenylsilyl-2,5-bis(hydroxymethyl) pyrrolidine 3 (a partially protected DGDP), and the appropriated ylides, followed by cyclization through an internal reductive amination process of the resulting alpha,beta-unsaturated ketone 7 and aldehyde 8, respectively, and total deprotection. (C) 2004 Elsevier Ltd. All rights reserved.

  (1R,2R,3S,5R,7aR)-1,2-二羟基-3-(羟甲基)-5-甲基吡咯烷二酮 [(+)-3-表海葱素 A(3)] 1 和 (1R,2R,3S,7aR)-1,2-二羟基-3-(羟甲基)吡咯烷二酮 [(+)-3-表海葱素 A(2)] 2 是通过 Wittig 方法[1](使用由 (2R,3R,4R,5S)-3,4-二苯氧基-N-苯氧羰基-2'-O-(特丁基二苯基)硅基-2,5-双(羟甲基)吡咯烷[2]（部分保护的 DGDP）制备的醛 6 以及相应的亚甲基, 然后分别通过 α,β-不饱和酮 7 和醛 8 的内源性还原胺化步骤进行环化, 最后完成完全脱保护而合成的。 (C) 2004 Elsevier Ltd. 保留所有权利。 [1] Wittig 方法：一种用于构建碳-碳双键的化学反应方法，通常涉及将醛或酮与 Wittig 试剂（如亚甲基化合物）反应生成烯烃。 [2] DGDP：二羟基-PDOT（双(羟甲基)吡咯烷)的缩写形式。
• A practical route to partially protected pyrrolidines as precursors for the stereoselective synthesis of alexines
  作者：Isidoro Izquierdo Cubero、Maria T. Plaza López-Espinosa、Rafael Robles Dı́az、Francisco Franco Montalbán

  DOI：10.1016/s0008-6215(00)00319-0

  日期：2001.2

  Either 3-O-benzoyl- (2a) or 3-O-benzyl-1,2-O-isopropylidene-beta-D-fructopyranose (2b) were regioselectively O-benzylated at C-4 to give 4a and 4b, respectively, which were transformed into 5-azido-3-O-benzoyl-4-O-benzyl- (6a) and 5-azido-3,4-di-O-benzyl-5-deoxy-1,2-O-isopropylidene-alpha-L-sorbopyranose (6b) by nucleophilic displacement of the corresponding 5-O-mesyl derivatives 5a and 5b by sodium azide in DMF, respectively. Compound 6b was also prepared from 4b in one step by the Mitsunobu methodology. Deacetonation of 6a and 6b gave the partially protected free azidouloses 8a and 8b, respectively, that were protected as their 1-O-TBDPS derivatives 9a and 9b. Hydrogenation of 9b over Raney nickel gave stereoselectively (2R,3R,4R,5S)-3,4-dibenzyloxy-2'-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine (12) which was identified by transformation into the well known (2R,3R,4R,5S)-3,4-dihydroxy-2,5-bis(hydroxymethyl)pyrrolidine (1, DGDP).