19089-97-5Relevant articles and documents
Syntheses and properties of silicon- and germanium-containing α-amino acids and peptides: A study on C/Si/Ge bioisosterism
Tacke, Reinhold,Merget, Markus,Bertermann, Ru?diger,Bernd, Michael,Beckers, Thomas,Reissmann, Thomas
, p. 3486 - 3497 (2008/10/08)
The unnatural silicon-containing α-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 α-amino acids (R)- and (S)-H2NCH(CH2GeMe3)COOH [(R)-3 and (S)-3] and (R)-H2NCH(CH2GeMe2Ph)COOH [(R)-5] were prepared 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 (≥99percent ee) compounds. The (R)- and (S)-enantiomers of β-(trimethylsilyl)alanine [(R)-2 and (S)-2] and β-(trimethylgermyl)alanine [CR)-3 and (S)-3] are sila-analogues and germa-analogues, respectively, of the (S)- and (R)-enantiomers of the nonproteinogenic amino acid β-tert-butylalanine [(S)- and (R)-H2NCH(CH2CMe3)COOH; (S)-l and (R)-1]. The C/Si/Ge-analogous (L-configurated) amino acids (S)-l, (R)-2, and (R)-3 were 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-Nal1-4-Cl-D-Phe2-D-Pal3-Ser 4-Me3El-Ala5-D-Cit6-Leu 7-Arg8-Pro9-D-Ala10-NH2 (7, El = C; 8, El = Si; 9, El = Ge)]. The C/Si/Ge analogues 7-9 are derivatives of the GnRH antagonist CetrorelixINN, 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.
(Acetoxymethyl)methylphenylgermane: Synthesis, Thermal Behaviour and Olfactoric Properties
Tacke, Reinhold,Wiesenberger, Frank
, p. 275 - 279 (2007/10/02)
(Acetoxymethyl)methylphenylgermane was synthesized by a five-step synthesis starting from trichloro(chloromethyl)germane PhCl2GeCH2Cl -> PhMeGe(Cl)CH2Cl -> PhMeGe(OAc)CH2OAc -> PhMeGe(H)CH2OH -> PhMeGe(H)CH2OAc >.The germane 1c and its carbon analogue PhMeC(H)CH2OAc (1a) are thermally stable (solutions in C6D6; 160 deg C, 48 h), whereas the structurally analogous silane PhMeSi(H)CH2OAc (1b) undergoes a rearrangement upon heating (formation of the silane PhMe2SiOAc; half-life in C6D6 at 135 deg C: 7,7 h).By analogy to the perfume 1a (hydratropyl acetate) and its silicon analogue 1b (sila-hydratropyl acetate), the germane 1c (germa-hydratropyl acetate) exhibits a sweet-floral odor.Despite of some differences, the olfactoric properties of the C/Si/Ge-analogues 1a/1b/1c are mainly characterized by analogies.
