359766-55-5Relevant academic research and scientific papers
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
Merget, Markus,Günther, Kurt,Bernd, Michael,Günther, Eckhard,Tacke, Reinhold
, p. 183 - 194 (2001)
Two novel efficient methods for the synthesis of racemic silicon- and germanium-containing α-amino acids of the formula type rac-H2NCH(CH2ElR3)COOH (El=Si, Ge; R=organyl), starting from 3,6-diethoxy-2,5-dihydropyrazine, have been developed. Racemic α-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 α-amino acids (R)-2, (S)-2, (R)-3, and (S)-3. The (R)- and (S)-enantiomers of β-(trimethylsilyl)alanine [(R)- and (S)-2] and β-(trimethylgermyl)alanine [(R)- and (S)-3] are sila-analogs and germa-analogs, respectively, of the antipodes of the non-proteinogenic α-amino acid β-tert-butylalanine [(S)- and (R)-H2NCH(CH2CMe3)COOH; (S)- and (R)-1]. Starting from the N-Fmoc-protected C/Si/Ge-analogous (D-configurated) α-amino acids (R)-1, (S)-2, and (S)-3, the C/Si/Ge-analogous decapeptides 7-9 [Ac-D-Nal1-4-Cl-D-Phe2-D-Pal3-Ser 4-N-Me-Tyr5-D-Hci6-Nle7-Arg 8-Pro9-D-Me3El-Ala10-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.
