(2S,3R)-N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine | 123287-88-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S,3R)-N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine
• 英文别名: tert-butyl (2R,3R)-3-(tert-butyldimethylsiloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate；(2S,3R)-tert-butyl 3-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate；(2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethylpyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2R,3R)-3-tert-butyldimethylsilyloxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate；tert-butyl (2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 123287-88-7
• 化学式: C₁₆H₃₃NO₄Si
• 分子量: 331.528
• InChiKey: MGNXUUUQPBTDNG-CHWSQXEVSA-N

物化性质

• 沸点：
  373.4±27.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3R)-N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine 在 三乙基硅烷 、 正丁基锂 、 二甲基亚砜 、 三乙胺 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 (2R,3R)-1-(Benzyloxycarbonyl)-2-<(3-methoxyphenyl)-methyl>pyrrolidin-3-yl S-Methyl Xanthate
  参考文献：
  名称：

  Asymmetric intramolecular amidation of N-(tert-butoxycarbonyl)-3-hydroxy-4-pentenylamine. A new entry to chiral building blocks for the synthesis of biologically active nitrogen-containing compounds

  摘要：

  Sharpless reaction of racemic N-(tert-butoxycarbonyl)-3-hydroxy-4-pentenylamine (1) leads to both an asymmetric kinetic resolution to provide optically active 1, which was subsequently used for intramolecular amidomercuration, and asymmetric epoxidation followed by concomitant cyclization into optically active cis-3-hydroxy-2-(hydroxymethyl)pyrrolidine (3). Optically active 1 and 3 have been expediently used as chiral building blocks in the asymmetric synthesis of several biologically active natural products.

  DOI：

  10.1021/jo00001a045
• 作为产物：
  描述：

  (2S,3R)-N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilyloxy)-2-pyrrolidinecarboxylic acid methyl ester 在 三乙基硼氢化锂 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3R)-N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine
  参考文献：
  名称：

  Discovery of Potent and Muscle Selective Androgen Receptor Modulators through Scaffold Modifications

  摘要：

  A novel series of imidazolin-2-ones were designed and synthesized as highly potent, orally active and muscle selective androgen receptor modulators (SARMs), with most of the compounds exhibiting low nM in vitro potency in androgen receptor (AR) binding and functional assays. Once daily oral treatment with the lead compound 11a (AR K-i = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in rats demonstrated that the lead compound 11a had oral bioavailability of 65% and a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the SARMs in this series are expected to provide beneficial anabolic effects on muscle with minimal androgenic effects on prostate tissue.

  DOI：

  10.1021/jm070312d

文献信息

• Synthetic studies of the detoxin complex. I. total synthesis of (-) detoxinine
  作者：W.R. Ewing、B.D. Harris、K.L. Bhat、M.M. Joullie'

  DOI：10.1016/0040-4020(86)80005-9

  日期：1986.1

  A total synthesis of (-) detoxinine (1), the parent amino acid of the detoxin complex is reported. Two different routes to key intermediate 8a were developed: one from an acyclic precursor and the other from L-proline. The elaboration of 8a to 1 employed a stereoselective aldol condensation.

  据报道，共合成了排毒复合物的母体氨基酸（-）排毒素（1）。已开发出两种通往关键中间体8a的不同途径：一种途径来自无环前体，另一种途径来自L-脯氨酸。对8a至1的修饰采用了立体选择性醛醇缩合。
• Asymmetric Syntheses of All Stereoisomers of 3-Hydroxyproline; A Constituent of Several Bioactive Compounds
  作者：Srivari Chandrasekhar、Togapur Kumar

  DOI：10.1055/s-0032-1316734

  日期：——

  3-hydroxyproline, and its derivatives have been achieved enantioselectively by employing Sharpless asymmetric epoxidation and reductive cyclization as the key steps. Synthesis of an unusual β-hydroxy-α-amino acid, 3-hydroxyproline, and its derivatives have been achieved enantioselectively by employing Sharpless asymmetric epoxidation and reductive cyclization as the key steps.

  摘要 通过使用Sharpless不对称环氧化和还原环化作为关键步骤，对映体选择性合成了一种不寻常的β-羟基-α-氨基酸，3-羟基脯氨酸及其衍生物。 通过使用Sharpless不对称环氧化和还原环化作为关键步骤，对映体选择性合成了一种不寻常的β-羟基-α-氨基酸，3-羟基脯氨酸及其衍生物。
• [EN] PYRROLIDINE OREXIN RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR DE L'OREXINE DE TYPE PYRROLIDINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2020167701A1

  公开（公告）日：2020-08-20

  The present invention is directed to pyrrolidine compounds which are agonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及吡咯烷化合物，其是促进促觉素受体的激动剂。本发明还涉及所述化合物在潜在的治疗或预防神经系统和精神疾病中的用途，这些疾病和疾病中涉及促觉素受体。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在的预防或治疗涉及促觉素受体的疾病中的用途。
• Chemoenzymatic synthesis of (2S,3R)-3-hydroxyproline from cyclopentadiene
  作者：Hari Sundram、Adam Golebiowski、Carl R. Johnson

  DOI：10.1016/0040-4039(94)88202-9

  日期：1994.9

  Amido-alcohol 4, derived from cyclopentadiene and resolved using Candida antarctica lipase B-mediated transacetylation, was transformed to (2R, 3R)-3-hydroxy-2-hydroxymethyl-pyrrolidine (2) and (2S, 3R)-3-hydroxyproline (1).

  衍生自环戊二烯并使用南极假丝酵母脂肪酶B介导的反乙酰化作用拆分的酰胺醇4转化为（2 R，3 R）-3-羟基-2-羟甲基-吡咯烷（2）和（2 S，3 R） -3-羟基脯氨酸（1）。
• Inhibitors of HIV protease
  申请人：Sankyo Company, Limited

  公开号：US05629406A1

  公开（公告）日：1997-05-13

  Compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen, alkyl, aralkyl, --COR.sup.a, --COR.sup.b, --CSR.sup.a, --CSR.sup.b, --SO.sub.2 R.sup.b, --CONHR.sup.b, --CSNHR.sup.b, --CONR.sup.b R.sup.b or --CSNR.sup.b R.sup.b ; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen, alkylidene, substituted alkyl, or R.sup.b ; R.sup.4 is optionally substituted alkyl, cycloalkyl, or aryl; R.sup.5 is R.sup.b O--, R.sup.b R.sup.b N--, R.sup.b HN--, aralkyloxycarbonyloxy or aralkyloxycarbonylamino, or R.sup.5 is --(CH.sub.2).sub.p --D--(CH.sub.2).sub.r --, where D is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH.sub.2 .dbd.CH.sub.2)-- or --NHCO--; and p and r are each 0 or an integer from 1 to 5; A is --(CH.sub.2).sub.m --B--(CH.sub.2).sub.n -- where B is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH.sub.2 .dbd.CH.sub.2)-- or --NHCO--; and m and n are each 0 or an integer from 1 to 5; R.sup.a is alkoxy, aralkyloxy, aryloxy or alkoxycarbonyl; R.sup.b is optionally substituted alkyl, cycloalkyl, heterocyclic, aryl or arylalkenyl; and pharmaceutically acceptable salts and esters thereof and pro-drugs therefor, have the ability to inhibit the activity of HIV protease and may thus be used for the treatment and prophylaxis of AIDS.

  化学式（I）的复合物：##STR1## 其中：R.sup.1是氢，烷基，芳基烷基，--COR.sup.a，--COR.sup.b，--CSR.sup.a，--CSR.sup.b，--SO.sub.2 R.sup.b，--CONHR.sup.b，--CSNHR.sup.b，--CONR.sup.b R.sup.b或--CSNR.sup.b R.sup.b; R.sup.2是氢或烷基; R.sup.3是氢，烷基，取代烷基或R.sup.b; R.sup.4是可选的取代烷基，环烷基或芳基; R.sup.5是R.sup.b O--，R.sup.b R.sup.b N--，R.sup.b HN--，芳基烷氧羰氧基或芳基烷氧羰氨基，或R.sup.5是--(CH.sub.2).sub.p --D--(CH.sub.2).sub.r --，其中D是单键，羰基，氧，硫，--NH--，--(CH.sub.2.dbd.CH.sub.2)--或--NHCO--; p和r分别为0或1至5的整数; A是--(CH.sub.2).sub.m --B--(CH.sub.2).sub.n --，其中B是单键，羰基，氧，硫，--NH--，--(CH.sub.2.dbd.CH.sub.2)--或--NHCO--; m和n分别为0或1至5的整数; R.sup.a是烷氧基，芳基烷氧基，芳氧基或烷氧羰基; R.sup.b是可选的取代烷基，环烷基，杂环基，芳基或芳基烯基; 其药学上可接受的盐和酯以及其前药，具有抑制HIV蛋白酶活性的能力，因此可用于治疗和预防艾滋病。