(4S,5R)-4-羟基-5-(羟基甲基)-L-脯氨酸 | 95863-87-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (4S,5R)-4-羟基-5-(羟基甲基)-L-脯氨酸
• 英文名称: (2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4S,5R)-4-hydroxy-5-hydroxymethyl proline；(2S,4S,5R)-(-)-bulgecinine；(-)-bulgecinine；bulgecinine
• CAS: 95863-87-9
• 化学式: C₆H₁₁NO₄
• 分子量: 161.158
• InChiKey: AEWQBAFSXFXHIT-LMVFSUKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S,5R)-4-羟基-5-(羟基甲基)-L-脯氨酸 在 碳酸氢钠 、 N,N'-二环己基碳二亚胺 作用下， 以 水 、 乙腈 为溶剂， 反应 5.0h， 生成 (2S,4S,5R)-4-Hydroxy-5-hydroxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-(3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl) ester
  参考文献：
  名称：

  Structures of bulgecins, bacterial metabolites with bulge-inducing activity

  摘要：

  DOI：

  10.1016/s0040-4020(01)91497-8
• 作为产物：
  描述：

  (2S,4S)-Methyl 4-acetoxy-1-<<2-(trimethylsilyl)ethyl>oxycarbonyl>pyrrolidine-2-carboxylate 在 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 硫酸 、 camphor-10-sulfonic acid 、 四丁基氟化铵 、 六正丁基二锡 、 四乙基对甲苯磺酸铵 、 臭氧 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 溶剂黄146 、 苯 为溶剂， 反应 37.0h， 生成 (4S,5R)-4-羟基-5-(羟基甲基)-L-脯氨酸
  参考文献：
  名称：

  Electrochemical oxidation of proline derivatives: total syntheses of bulgecinine and bulgecin C

  摘要：

  The influence of structure on the efficiency of the electrochemical C-5 oxidation of (2S,4S)-hydroxyproline carbamate esters is presented. Optimum methoxylation was observed with (2S,4S)-4-acetoxy-1,2-pyrrolidine-dicarboxylic acid 2-methyl 1-(2-(trimethylsily)ethyl) ester (19). The corresponding C-5 methoxy derivative 20 was converted into bulgecinine (4) via a stereospecific radical homologation to incorporate the C-5 hydroxymethyl substituent. Bulgecin C (1c) was prepared via a beta-stereoselective glycosidation reaction using a 2-azido-2-deoxy-alpha-D-glucopyranosyl trichloroacetimidate derivative, regiospecific C-4' sulfation, and deprotection.

  DOI：

  10.1021/jo00008a040

文献信息

• Asymmetric Alkylations of a Sultam-Derived Glycine Equivalent: Practical preparation of enantiomerically pure ?-amino acids
  作者：Wolfgang Oppolzer、Robert Moretti、Changyou Zhou

  DOI：10.1002/hlca.19940770823

  日期：1994.12.14

  products 3. Acidic hydrolysis of the pure products 3 gives (aminoacyl)sultams 4 which by mild saponification furnish pure α-amino acids 5 in good overall yields from 2, along with recovered auxiliary 1 (Scheme 1). Pure ω-protected α,ω-diamino acids and α-amino-ω-(hydroxyamino)acids 12–16 are readily accessible from (ω-haloacyl)sultams 3via reaction with N-nucleophiles followed by acidic and basic hydrolyses

  在无水介质中，手性甘氨酸衍生物2与“活化的”有机卤化物在超声辅助的相转移催化下或活化和非活化的有机卤化物在无水介质中的烷基化提供了（大部分是结晶的）烷基化产物3。纯产物3的酸性水解得到（氨基酰基）sultams 4，其通过温和皂化以2的良好总产率提供纯的α-氨基酸5以及回收的助剂1（方案1）。纯的ω-保护的α，ω-二氨基酸和α-氨基-ω-（羟基氨基）酸12-16可容易地从（ω-卤代酰基）sultams 3通过与N-亲核试剂反应，然后进行酸性和碱性水解（方案2）。提出了通过对其N-（3,5-二硝基苯甲酰基）脯氨酰基衍生物17的HPLC分析来可靠测定α-氨基酸的对映体纯度的方法。
• An efficient route to 1,3-amino hydroxyl system via electrophilic lactonization of 2-amino-4-pentenoic acid derivatives. Stereoselective synthesis of (−)-bulgecinine
  作者：Yasufumi Ohfune、Keiko Hori、Masahiro Sakaitani

  DOI：10.1016/s0040-4039(00)85403-9

  日期：1986.1

  Several γ-hydroxy-α-amino acid systems were prepared stereoselectively from 2-amino-4-pentenoic acid derivatives using electrophilic lactonization. This strategy was applied to the synthesis of a highly functionalized proline analogue, (−)-bulgecinine (4).

  使用亲电子内酯化作用，由2-氨基-4-戊烯酸衍生物立体选择性地制备了几种γ-羟基-α-氨基酸系统。该策略被用于合成高度功能化的脯氨酸类似物（-）-bulgecinine（4）。
• An efficient synthesis of (-)-bulgecinine
  作者：Yoshiro Hirai、Takashi Terada、Yoshiko Amemiya、Takefumi Momose

  DOI：10.1016/s0040-4039(00)74771-x

  日期：1992.12

  A highly stereoselective synthesis of (-)-bulgecinine (1) via the pyrrolido[1,2-c]oxazolidin-3-one system (2) has been achieved by starting with the asymmetric epoxidation of the twin allyl alcohol system (6). The transformation of note includes the palladium-catalyzed N→π cyclization leading exclusively to a trans-2,5-disubstituted pyrrolidine.

  （ - ） -的高度立体选择性合成bulgecinine（1）经由所述pyrrolido [1,2 Ç ]恶唑烷-3-一个系统（2）已通过与双烯丙醇系统的不对称环氧化原料（实现6） 。note的转换包括钯催化的N →π环化，仅导致反式-2,5-二取代的吡咯烷。
• Palladium-Catalyzed DYKAT of Butadiene Monoepoxide: Enantioselective Total Synthesis of (+)-DMDP, (−)-Bulgecinine, and (+)-Broussonetine G
  作者：Barry M. Trost、Daniel B. Horne、Michael J. Woltering

  DOI：10.1002/chem.200600202

  日期：2006.8.25

  butadiene monoxide allows for the expedient synthesis of trans- and cis-2,5-dihydropyrroles. The versatility of these chiral synthons towards the synthesis of a wide variety of iminosugar natural products was demonstrated with the short and high yielding asymmetric syntheses of (+)-DMDP, and (-)-bulgecinine. In addition, the first total synthesis of (+)-broussonetine G, a potent glycosidase inhibitor, is described

  胺与两当量一氧化丁二烯的钯催化的不对称烯丙基烷基化反应可方便地合成反式和顺式-2,5-二氢吡咯。这些手性合成子对多种亚氨基糖天然产物合成的多功能性通过（+）-DMDP和（-）-bulgecinine的短而高产率的不对称合成得到了证明。另外，描述了一种有效的糖苷酶抑制剂（+）-布洛涅汀G的第一个全合成，以及其相对和绝对立体化学构型的分配。
• Polyhydroxylated pyrrolidine and 2-oxapyrrolizidine as glycosidase inhibitors
  作者：Jen-Tsung Wang、Ting-Chien Lin、Ying-Hsuan Chen、Chun-Hung Lin、Jim-Min Fang

  DOI：10.1039/c3md00033h

  日期：——

  Using D-serine as a chiral precursor, a polyhydroxylated pyrrolidine (1), its derivatives bearing carboxylate, phosphate and phosphonate groups (2–4) and an oxapyrrolizidine (5) were synthesized. The pyrrolidine ring was formed by intramolecular amino-mercuration. The bicyclic scaffold of oxapyrrolizidine was further constructed by an intramolecular attack of the carbamate group on the iodomethyl group. Compounds 1 and 5 were found to inhibit β-glucosidase and α-galactosidase, respectively, in a competitive manner, whereas compounds 2, 3 and 4 did not produce significant inhibition against glycosidases.

  使用 D-丝氨酸作为手性前体，合成了多羟基化吡咯烷 (1)、其带有羧酸酯、磷酸酯和膦酸酯基团的衍生物 (2-4) 以及奥沙吡咯里西啶 (5)。通过分子内氨基汞化形成吡咯烷环。通过氨基甲酸酯基团对碘甲基的分子内攻击进一步构建了奥沙吡咯里西啶的双环支架。发现化合物1和5分别以竞争性方式抑制β-葡萄糖苷酶和α-半乳糖苷酶，而化合物2、3和4对糖苷酶没有产生显着的抑制作用。