869772-05-4Relevant academic research and scientific papers
Non-phosgene route to unsymmetrical ureas from N-Cbz-α-amino acid amides
Ghazvini Zadeh, Ebrahim H.,Abo-Dya, Nader E.,Sotuyo, Ania C.,Ghiviriga, Ion,Hall, C. Dennis
, p. 5467 - 5469 (2013/09/23)
A convenient method toward the synthesis of α-amino acid-derived unsymmetrical ureas 2 is described herein. This route involves an interesting rearrangement of amides of N-Cbz-α-amino acids 1, which presumably entails the intermediacy of hydantoins that is followed by hydrolysis to afford unsymmetrical ureas 2 in quantitative yields and high purity.
Chemical ligation of S-scylated cysteine peptides to form native peptides via 5-, 11-, and 14-membered cyclic transition states
Katritzky, Alan R.,Tala, Srinivasa R.,Abo-Dya, Nader E.,Ibrahim, Tarek S.,El-Feky, Said A.,Gyanda, Kapil,Pandya, Keyur M.
experimental part, p. 85 - 96 (2011/04/12)
Cysteine-containing dipeptides 3a-l, (3b+3b′) (compound numbers in parentheses are used to indicate racemic mixtures; thus (3b+3b′) is the racemate of 3b and 3b′), and tripeptide 13 were synthesized in 68-96% yields by acylation of cysteine with N-(Pg-α-aminoacyl)- and N-(Pg-α-dipeptidoyl)benzotriazoles (where Pg stands for protecting group in the nomenclature for peptides throughout the paper) in the presence of Et3N. Cysteine-containing peptides 3a-l and 13 were S-acylated to give S-(Pg-α-aminoacyl)dipeptides 5a-l and S-(Pg-α-aminoacyl) tripeptide 14 without racemization in 47-90% yields using N-(Pg-α- aminoacyl)benzotriazoles 2 in CH3CN-H2O (7:3) in the presence of KHCO3. (In our peptide nomenclature, the prefixes di-, tri-, etc. refer to the number of amino acid residues in the main peptide chain; amino acid residues attached to sulfur are designated as S-acyl peptides. Thus we avoid use of the prefix "iso".) Selective S-acylations of serine peptide 3k and threonine peptide 3l containing free OH groups were thus achieved in 58% and 72% yield, respectively. S-(Pg-α-aminoacyl)cysteines 4a,b underwent native chemical ligations to form native dipeptides 3f,i via 5-membered cyclic transition states. Microwave irradiation of S-(Pg-α-aminoacyl)tripeptide 15 and S-(Pg-α-aminoacyl)tetrapeptide 17 in the presence of NaH2PO4/Na2HPO 4 buffer solution at pH 7.8 achieved chemical ligations, involving intramolecular migrations of acyl groups, via 11- and 14-membered cyclic transition states from the S-atom of a cysteine residue to a peptide terminal amino group to form native peptides 19 and 20 in isolated yields of 26% and 23%, respectively.
Benzotriazole-mediated syntheses of depsipeptides and oligoesters
Avan, Ilker,Tala, Srinivasa R.,Steel, Peter J.,Katritzky, Alan R.
scheme or table, p. 4884 - 4893 (2011/07/30)
Reactions of O-Pg(α-hydroxyacyl)benzotriazoles with (a) unprotected α-hydroxycarboxylic acids, (b) amino acids, and (c) amines afforded, respectively, chirally pure (a) oligoesters, (b) depsidipeptides, and (c) amide conjugates (yields 52-94%). N-Pg(α-Ami
Convenient synthesis of C-terminal di- and tri-peptide amides from N-protected dipeptidoylbenzotriazoles
Celik, Ilhami,Abdel-Fattah, Ashraf A.A.
experimental part, p. 4923 - 4929 (2009/10/09)
N-Protected dipeptidoylbenzotriazoles react with aqueous ammonia to give dipeptide primary amides (77-98%) and with N-unprotected α-amino amides to afford tripeptide primary amides (82-86%).
The efficient preparation of di- and tripeptides by coupling N-(Cbz- or Fmoc-α-aminoacyl)benzotriazoles with unprotected amino acids
Katritzky, Alan R.,Angrish, Parul,Suzuki, Kazuyuki
, p. 411 - 424 (2007/10/03)
N-(Cbz- or Fmoc-α-aminoacyl)benzotriazoles 2 and N-protected peptidoylbenzotriazoles 6 are coupled in aqueous acetonitrile solution with free amino acids or dipeptides to prepare: (i) 22 chirally pure dipeptides 5a-v (in an average yield of 82%) from N-(Cbz- or Fmoc-α-aminoacyl)benzotriazoles 2 and unprotected amino acids, (ii) five chiral tripeptides 7a-e (in an average yield of 75%) from N-protected peptidoylbenzotriazoles 6 and unprotected amino acids, (iii) one chiral tripeptide 7g (62%) from N-(Cbz- or Fmoc-α- aminoacyl)benzotriazole 2a and the free dipeptide 8. In all, N-(Cbz- or Fmoc-α-aminoacyl)benzotriazole derivatives of 17 of the 20 naturally occurring amino acids were used, including those containing the following unprotected side chain functionalities: alcoholic -OH (Ser), indole -NH (Trp), imidazole -NH, phenolic -OH (Tyr), -CONH2 (Gln, Asn), -SH (Cys), -CO2H (Glu, Asp), and -S-S (Cystine). Support for the complete retention of chirality was obtained by parallel experiments involving D-Ala, L-Ala, and DL-Ala for the preparation of di- and tripeptides. This and other evidence for chiral integrity was supported by NMR and HPLC analyses. Georg Thieme Verlag Stuttgart.
