(2S,4R)-1-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)-2-methylpyrrolidine-2-methanol | 400724-45-0

• 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,4R)-1-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)-2-methylpyrrolidine-2-methanol
• 英文别名: Boc-aMeHyp(TBDMS)(TBDMS)-ol；tert-butyl (2S,4R)-4-[tert-butyl(dimethyl)silyl]oxy-2-(hydroxymethyl)-2-methylpyrrolidine-1-carboxylate
• CAS: 400724-45-0
• 化学式: C₁₇H₃₅NO₄Si
• 分子量: 345.555
• InChiKey: RLASPMLEFLUWPF-DYVFJYSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  23
• 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,4R)-1-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)-2-methylpyrrolidine-2-methanol 在 4-二甲氨基吡啶 、 四丁基氟化铵 、 三乙胺 、 silver(l) oxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 6.0h， 生成 tert-butyl (2S,4R)-2-(methoxymethyl)-2-methyl-4-(4-methylphenyl)sulfonyloxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis of 2,2-Disubstituted Pyrrolidine-4-carboxylic Acid Derivatives and Their Incorporation into β-Peptide Oligomers

  摘要：

  We have recently shown that members of a new class of P-peptides, containing 2,2-disubstituted pyrrolidine-4-carboxylic acid residues, display discrete conformational preferences despite the impossibility of internal hydrogen bonding (Huck et al. J. Am. Chem. Soc. 2003, 125, 9035). Here we describe the synthesis of a variety of 2,2-disubstituted pyrrolidine-4-carboxylic derivatives that bear a diverse set of side chains and protecting groups suitable for oligomer synthesis. In addition, we discuss coupling methods for construction of oligomers in solution and on solid phase. Nonhydrogen bonded foldamers such as those generated from 2,2-disubstituted pyrrolidine-4-carboxylic acids may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.

  DOI：

  10.1021/jo048639z
• 作为产物：
  描述：

  (2S,4R)-4-(tert-butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 以81%的产率得到(2S,4R)-1-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)-2-methylpyrrolidine-2-methanol
  参考文献：
  名称：

  Synthesis of 2,2-Disubstituted Pyrrolidine-4-carboxylic Acid Derivatives and Their Incorporation into β-Peptide Oligomers

  摘要：

  We have recently shown that members of a new class of P-peptides, containing 2,2-disubstituted pyrrolidine-4-carboxylic acid residues, display discrete conformational preferences despite the impossibility of internal hydrogen bonding (Huck et al. J. Am. Chem. Soc. 2003, 125, 9035). Here we describe the synthesis of a variety of 2,2-disubstituted pyrrolidine-4-carboxylic derivatives that bear a diverse set of side chains and protecting groups suitable for oligomer synthesis. In addition, we discuss coupling methods for construction of oligomers in solution and on solid phase. Nonhydrogen bonded foldamers such as those generated from 2,2-disubstituted pyrrolidine-4-carboxylic acids may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.

  DOI：

  10.1021/jo048639z

文献信息

• Diastereoselective synthesis of 2-alkylated 4-silyloxyproline esters
  作者：Tatsunori Sato、Satomi Kawasaki、Nobuo Oda、Shôko Yagi、Serry A. A. El Bialy、Jun'ichi Uenishi、Masashige Yamauchi、Masazumi Ikeda

  DOI：10.1039/b105238c

  日期：2001.10.11

  Treatment of the 4-silyloxy-N-Boc-L-proline methyl ester 1 with allyl bromide in the presence of LDA in THF at −78 °C gives a mixture of the (2S,4R)- and (2R,4R)-2-(prop-2-enyl)-4-silyloxy-N-Boc-L-proline esters 2a and 2b in 75% combined yield in the ratio 53 ∶ 47. In contrast, similar treatment of the (−)- and (+)-menthyl esters 5 and 6 gives a mixture of allylated products 7a,b and 8a,b in the ratio 75 ∶ 25 and 89 ∶ 11, respectively. Reaction of 6 with methyl iodide and propyl iodide also give the corresponding 2-alkylated esters 16a and 16b in a highly diastereoselective manner (94 ∶ 6 and 93 ∶ 7, respectively).

  在-78°C下，将4-硅氧基-N-Boc-L-脯氨酸甲酯1与烯丙基溴在LDA和THF的存在下反应，得到了(2S,4R)-和(2R,4R)-2-(丙-2-烯基)-4-硅氧基-N-Boc-L-脯氨酸酯2a和2b的混合物，总产率为75%，其比例为53∶47。相比之下，类似处理(-)和(+)-薄荷醇酯5和6则分别得到烯丙基化产物7a,b和8a,b的混合物，比例分别为75∶25和89∶11。此外，6与甲基碘和丙基碘反应也以高度立体选择性（分别为94∶6和93∶7）得到相应的2-烷基化酯16a和16b。