Semisynthesis of linear gramicidins using diphenyl phosphorazidate (DPPA).
Sequential HPLC analysis has been used to optimize a synthetic scheme for the preparation of semisynthetic position 1 analogues of the channel-forming pentadecapeptide, gramicidin A. Diphenyl phosphorazidate (DPPA) was more efficient than dicyclohexylcarbodiimide (DCC) for the coupling of N-formyl amino acids to des(formyl-valyl) gramicidin A. The DPPA coupling proceeds rapidly, and with high yield, at 0 degree. The absence of significant (less than 0.1%) racemization is demonstrated by the lack of electrophysiologically active formyl-L-valine gramicidin A in preparations of formyl-D-valine gramicidin A. This scheme has proved useful for the preparation of microgram to gram amounts of position-1-substituted gramicidin analogues suitable for crystallography and electrophysiology. Details of the techniques for the preparation of these highly purified analogues are discussed.
L B
LB
Weiss
R E
RE
Koeppe
D001386:Azides; D002851:Chromatography, High Pressure Liquid; D006096:Gramicidin / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007473:Ion Channels / Q000378:metabolism; D008954:Models, Biological; D013329:Structure-Activity Relationship
D001386:Azides; D007202:Indicators and Reagents; D007473:Ion Channels; D006096:Gramicidin; C007523:diphenylphosphorazidate