Total synthesis of cyclosporin O: exploring the utility of Bsmoc-NMe-amino acid fluorides and KOAt.
Cyclosporin O (CyO), an immunosuppressent cyclic undecapeptide, was synthesized by convergent approach employing Bsmoc-Nmethyl amino acid fluorides and Potassium Salt of 7-Aza-1-hydroxybenzotriazole (KOAt) in solution by stepwise assembly. The couplings were found to be epimerisation free. The difficulty in the coupling of four consecutive N-methyl amino acids at position 8, 9, 10 and 11 was overcome by repeating the coupling thrice at these critical positions. All the ten protected peptide fragments of CyO starting from the dipeptide to the undecapeptide and final protected as well as CyO were isolated and fully characterized.
Sureshbabu
Vommina Venkata
VV
Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Bangalore University, Dr. B. R. Ambedkar Veedhi, Bangalore 560 001, India. hariccb@rediffmail.com
Tantry
Subramanyam J
SJ
Chennakrishnareddy
Gundala
G
Nagendra
Govindappa
G
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis; D003524:Cyclosporins / Q000138:chemical synthesis*; D005459:Fluorides / Q000138:chemical synthesis / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000138:chemical synthesis*; D014230:Triazoles / Q000138:chemical synthesis
D000596:Amino Acids; D001372:Aza Compounds; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D014230:Triazoles; C412021:cyclosporin O; D005459:Fluorides; C435757:1-hydroxy-7-azabenzotriazole