Total synthesis of cyclosporin O by convergent approach employing Fmoc-amino acid chlorides mediated by zinc dust.
An epimerization free and efficient total synthesis of immunosuppressant cyclosporin O (CsO) by step-by-step assembly of amino acids in solution phase is reported. The couplings were performed by employing Fmoc-amino acid chlorides and were mediated by zinc dust under neutral conditions. The yield and purity of the coupling of sterically hindered N-methylamino acids to N-methylamino acids at positions 8, 9, 10, and 11 were enhanced by repeating the coupling thrice at these particular junctures. All the 10 intermediate peptides pertaining to CsO and the final CsO were isolated and completely characterized through IR, 1H NMR, mass spectrometry, and HPLC techniques.
Tantry
Subramanyam J
SJ
Department of Studies in Chemistry, Central College Campus, Bangalore University, Bangalore, India.
Venkataramanarao
Rao
R
Chennakrishnareddy
Gundala
G
Sureshbabu
Vommina Venkata
VV
D000596:Amino Acids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000138:chemical synthesis*; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015032:Zinc / Q000737:chemistry*
D000596:Amino Acids; D003524:Cyclosporins; D006843:Hydrocarbons, Chlorinated; D007166:Immunosuppressive Agents; C412021:cyclosporin O; D015032:Zinc