(R)-2-amino-3-(trimethylgermyl)propionic acid | 288392-99-4

• 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
• 英文名称: (R)-2-amino-3-(trimethylgermyl)propionic acid
• 英文别名: (S)-2-amino-3-(trimethylgermyl)propionic acid；(R)-β-(trimethylgermyl)alanine；(S)-β-(trimethylgermyl)alanine；(2R)-2-amino-3-trimethylgermylpropanoic acid
• CAS: 288392-99-4
• 化学式: C₆H₁₅GeNO₂
• 分子量: 205.781
• InChiKey: IWLKRDVQRXDGEA-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.74
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-amino-3-(trimethylgermyl)propionic acid 、 氯甲酸-9-芴基甲酯 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以59%的产率得到(S)-N-[(fluoren-9-yl)methoxycarbonyl]-2-amino-3-(trimethylgermyl)propionic acid
  参考文献：
  名称：

  Syntheses of racemic and non-racemic silicon- and germanium-containing α-amino acids of the formula type H2NCH(CH2ElR3)COOH (El=Si, Ge; R=organyl) and incorporation of d-H2NCH(CH2SiMe3)COOH and d-H2NCH(CH2GeMe3)COOH into biologically active decapeptides: a study on C/Si/Ge bioisosterism

  摘要：

  Two novel efficient methods for the synthesis of racemic silicon- and germanium-containing a-amino acids of the formula type rac-H2NCH(CH2EIR3)COOH (El = Si, Ge; R = organyl), starting from 3,6-diethoxy-2,5-dihydropyrazine, have been developed. Racemic cc-amino acids synthesized: rac-H2NCH(CH2SiMe3)COOH (rac-2), rac-H2NCH(CH2GeMe3)COOH (rac-3), rac-H2NCH(CH2SiMe2Ph)COOH (rac-4), rac-H2NCH(CH2GeMe2Ph)COOH (rac-5), and rac-H2NCH(CH2SiMe2CH=CH2)COOH (rac-6). Preparative liquid-chromatographic resolution of rac-2 and rac-3 [CHIROBIOTIC T (glycopeptide Teicoplanin covalently linked to spherical silica gel) as the stationary phase] yielded the alpha -amino acids (R)-2, (S)-2, (R)-3, and (S)-3. The (R)- and (S)-enantiomers of beta-(trimethylsilyl)alanine [(R)- and (S)-2] and beta-(trimethylgermyl)alanine I(R)- and (S)-3] are sila-analogs and germa-analogs, respectively, of the antipodes of the non-proteinogenic alpha -amino acid beta -tert-butylalanine [(S)- and (R)-H2NCH(CH2CMe3)COOH; (S)- and (R)-1]. Starting from the N-Fmoc-protected C/Si/Ge-analogous (D-configurated) alpha -amino acids (R)-1, (S)-2, and (S)-3, the C/Si/Ge-analogous decapeptides 7-9 [Ac-D-Nal(1)-4-Cl-D-Phe(2)-D-Pal(3)-Ser(4)-N-Me-Tyr(5)-D-Hci(6)- Nle(7)-Arg(8)-Pro(9)-D-Me(3)El-Ala(10)-NH2 (7, El = C; 8, El = Si; 9, El = Ge)] were prepared by sequential solid-phase synthesis. The decapeptides 7-9 were studied in vitro in a functional assay using a recombinant cell line expressing the human GnRH receptor (agonist Triptorelin). Compounds 7-9 behaved as medium-potent GnRH antagonists, the antagonistic potencies of these three C/Si/Ge analogs being very similar. (C) 2001 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0022-328x(01)00783-5
• 作为产物：
  描述：

  (R)-2-amino-3-(trimethylgermyl)propionic acid ethyl ester 、 水 在 methyloxirane 作用下， 以 乙醇 、 水 为溶剂， 以64%的产率得到(R)-2-amino-3-(trimethylgermyl)propionic acid
  参考文献：
  名称：

  Syntheses and Properties of Silicon- and Germanium-Containing α-Amino Acids and Peptides:   A Study on C/Si/Ge Bioisosterism

  摘要：

  The unnatural silicon-containing alpha-amino acids (R)- and (S)-H2NCH(CH2SiMe3)COOH [(R)-2 and (S)-2], (R)-H2NCH(CH2SiMe2Ph)COOH [(R)-4], and (R)-H2NCH(CH2SiMe2CH=CH2)COOH [(R)-6] as well as the unnatural germanium-containing alpha-amino acids (R)- and (S)-H2NCH(CH2GeMe3)COOH [(R)-3 and (S)-3] and (R)-H2NCH(CH2GeMe2Ph)COOH [(R)-5] were prepare d in three-step syntheses, starting from (R)-3,6-diethoxy-2-isopropyl-2,5-dihydropyrazine [(R)-10]. All amino acids were isolated as enantiomerically pure (greater than or equal to 99% ee) compounds. The (R)- and (S)-enantiomers of beta-(trimethylsilyl)alanine [(R)-2 and (S)-2] and beta-(trimethylgermyl)alanine [(R)-3 and (S)-3] are sila-analogues and germa-analogues, respectively, of the (S)- and (R)-enantiomers of the nonproteinogenic amino acid beta-tert-butylalanine [(S)- and (R)-H2NCH(CH2CMe3)COOH; (S)-1 and (R)-1]. The C/Si/Ge-analogous (L-configurated) amino acids (S)-1, (R)-2, and (R)-3 mere treated with (fluoren-9-yl)methyl chloroformate to give the corresponding N-Fmoc derivatives (S)-26, (R)-27, and (R)-28. These N-Fmoc-protected amino acids were used as building blocks for the solid-phase syntheses of the C/Si/Ge-analogous decapeptides 7-9 [Ac-D-Nal(1)-4-Cl-D-Phe(2)-D-Pal(3)-Ser(4)-Me(3)El-Ala(5)-D-Cit(6)-Leu(7)-Arg(8)-Pro(9)-D-Ala(10)-NH2 (7, El = C; 8, El = Si; 9, El = Ge)]. The C/Si/Ge analogues 7-9 are derivatives of the GnRH antagonist Cetrorelix(TM), which bears an (S)-tyrosine residue [instead of the (S)-Me3C-Ala, (R)-Me3Si-Ala, or (R)-Me3Ge-Ala residue] in position 5 of its decapeptide backbone. The decapeptides 7-9 were studied in vitro in receptor binding and functional assays using recombinant cell lines expressing the human GnRH receptor. All compounds behaved as potent GnRH antagonists, the binding affinities and antagonistic potencies of the three C/Si/Ge analogues being quite similar. Compounds 7-9 were also studied for their in vivo activities in the male rat after s.c. administration. They produced both a strong testosterone suppression (single-dose treatment, 1.5 mg/kg) and a strong LH suppression (castrated male rat; single-dose treatment, 0.05 mg/kg). For the silicon- and germanium-containing decapeptides 8 and 9 the testosterone and LH suppression lasted for a significantly longer period of time compared with the effects of the carbon analogue 7.

  DOI：

  10.1021/om000169l

文献信息

• Syntheses of racemic and non-racemic silicon- and germanium-containing α-amino acids of the formula type H2NCH(CH2ElR3)COOH (El=Si, Ge; R=organyl) and incorporation of d-H2NCH(CH2SiMe3)COOH and d-H2NCH(CH2GeMe3)COOH into biologically active decapeptides: a study on C/Si/Ge bioisosterism
  作者：Markus Merget、Kurt Günther、Michael Bernd、Eckhard Günther、Reinhold Tacke

  DOI：10.1016/s0022-328x(01)00783-5

  日期：2001.5

  Two novel efficient methods for the synthesis of racemic silicon- and germanium-containing a-amino acids of the formula type rac-H2NCH(CH2EIR3)COOH (El = Si, Ge; R = organyl), starting from 3,6-diethoxy-2,5-dihydropyrazine, have been developed. Racemic cc-amino acids synthesized: rac-H2NCH(CH2SiMe3)COOH (rac-2), rac-H2NCH(CH2GeMe3)COOH (rac-3), rac-H2NCH(CH2SiMe2Ph)COOH (rac-4), rac-H2NCH(CH2GeMe2Ph)COOH (rac-5), and rac-H2NCH(CH2SiMe2CH=CH2)COOH (rac-6). Preparative liquid-chromatographic resolution of rac-2 and rac-3 [CHIROBIOTIC T (glycopeptide Teicoplanin covalently linked to spherical silica gel) as the stationary phase] yielded the alpha -amino acids (R)-2, (S)-2, (R)-3, and (S)-3. The (R)- and (S)-enantiomers of beta-(trimethylsilyl)alanine [(R)- and (S)-2] and beta-(trimethylgermyl)alanine I(R)- and (S)-3] are sila-analogs and germa-analogs, respectively, of the antipodes of the non-proteinogenic alpha -amino acid beta -tert-butylalanine [(S)- and (R)-H2NCH(CH2CMe3)COOH; (S)- and (R)-1]. Starting from the N-Fmoc-protected C/Si/Ge-analogous (D-configurated) alpha -amino acids (R)-1, (S)-2, and (S)-3, the C/Si/Ge-analogous decapeptides 7-9 [Ac-D-Nal(1)-4-Cl-D-Phe(2)-D-Pal(3)-Ser(4)-N-Me-Tyr(5)-D-Hci(6)- Nle(7)-Arg(8)-Pro(9)-D-Me(3)El-Ala(10)-NH2 (7, El = C; 8, El = Si; 9, El = Ge)] were prepared by sequential solid-phase synthesis. The decapeptides 7-9 were studied in vitro in a functional assay using a recombinant cell line expressing the human GnRH receptor (agonist Triptorelin). Compounds 7-9 behaved as medium-potent GnRH antagonists, the antagonistic potencies of these three C/Si/Ge analogs being very similar. (C) 2001 Elsevier Science B.V. All rights reserved.
• Syntheses and Properties of Silicon- and Germanium-Containing <i>α</i>-Amino Acids and Peptides:   A Study on C/Si/Ge Bioisosterism
  作者：Reinhold Tacke、Markus Merget、Rüdiger Bertermann、Michael Bernd、Thomas Beckers、Thomas Reissmann

  DOI：10.1021/om000169l

  日期：2000.9.1

  The unnatural silicon-containing alpha-amino acids (R)- and (S)-H2NCH(CH2SiMe3)COOH [(R)-2 and (S)-2], (R)-H2NCH(CH2SiMe2Ph)COOH [(R)-4], and (R)-H2NCH(CH2SiMe2CH=CH2)COOH [(R)-6] as well as the unnatural germanium-containing alpha-amino acids (R)- and (S)-H2NCH(CH2GeMe3)COOH [(R)-3 and (S)-3] and (R)-H2NCH(CH2GeMe2Ph)COOH [(R)-5] were prepare d in three-step syntheses, starting from (R)-3,6-diethoxy-2-isopropyl-2,5-dihydropyrazine [(R)-10]. All amino acids were isolated as enantiomerically pure (greater than or equal to 99% ee) compounds. The (R)- and (S)-enantiomers of beta-(trimethylsilyl)alanine [(R)-2 and (S)-2] and beta-(trimethylgermyl)alanine [(R)-3 and (S)-3] are sila-analogues and germa-analogues, respectively, of the (S)- and (R)-enantiomers of the nonproteinogenic amino acid beta-tert-butylalanine [(S)- and (R)-H2NCH(CH2CMe3)COOH; (S)-1 and (R)-1]. The C/Si/Ge-analogous (L-configurated) amino acids (S)-1, (R)-2, and (R)-3 mere treated with (fluoren-9-yl)methyl chloroformate to give the corresponding N-Fmoc derivatives (S)-26, (R)-27, and (R)-28. These N-Fmoc-protected amino acids were used as building blocks for the solid-phase syntheses of the C/Si/Ge-analogous decapeptides 7-9 [Ac-D-Nal(1)-4-Cl-D-Phe(2)-D-Pal(3)-Ser(4)-Me(3)El-Ala(5)-D-Cit(6)-Leu(7)-Arg(8)-Pro(9)-D-Ala(10)-NH2 (7, El = C; 8, El = Si; 9, El = Ge)]. The C/Si/Ge analogues 7-9 are derivatives of the GnRH antagonist Cetrorelix(TM), which bears an (S)-tyrosine residue [instead of the (S)-Me3C-Ala, (R)-Me3Si-Ala, or (R)-Me3Ge-Ala residue] in position 5 of its decapeptide backbone. The decapeptides 7-9 were studied in vitro in receptor binding and functional assays using recombinant cell lines expressing the human GnRH receptor. All compounds behaved as potent GnRH antagonists, the binding affinities and antagonistic potencies of the three C/Si/Ge analogues being quite similar. Compounds 7-9 were also studied for their in vivo activities in the male rat after s.c. administration. They produced both a strong testosterone suppression (single-dose treatment, 1.5 mg/kg) and a strong LH suppression (castrated male rat; single-dose treatment, 0.05 mg/kg). For the silicon- and germanium-containing decapeptides 8 and 9 the testosterone and LH suppression lasted for a significantly longer period of time compared with the effects of the carbon analogue 7.