Zur Struktur der Zuckerkomponente des Digitoxins. 47. Mitteilung über Herzglykoside

Abstract

Die Mikroanalysen wurden in verdankenswerter Weise im analytischen Laboratorium desZurchcr Institutes unter der Leitung von Herrn H. FROHOPER ausgefiihrt : die DEBYE-SCHERRER-Diagramme wurden von Herrn Dr. R. MULLER und die 1R.-Spektren von Herrn Dr. E. GANZ in den Physik-Laboratorien der CIBA ,4G. aufgenommen, wofur wir auch an dicser Stellc bestens danken mochten. SUMMARYCyclisation of active esters3) of the racemic tripeptides glycyl-glycyl-nL-phenylalanine and glycyl-DL-phenylalanyl-glycine as well as of the hexapeptide glycylglycyl-DL-phenylalanyl-glycyl-glycyl-DL-phenylalanine (unidentified mixture of diastereoisomers) has yielded as main product the meso-cyclohexapeptide, cyclo-glycyl-L-phenylalanyl-glycyl-glycyl-D-phenylalanyl-g~ycyl (IV) 5). This is proven by comparison of the X-ray powder diagram of the said product with those of the corresponding meso, L-L, D-D, and racemic cyclohexapeptides (Fig.1). The synthesis of these isomers by the azide pioceduree) is described. The hydrazide function was introduced in a protected form') early in the synthesis (as -NHNH*CO*OC(CH,),) and the blocking group (t-butoxy-carbonyl) removed in one of the last steps (schemes 2 and 3).The reported reactions constitute the fiist observation of stereospecific cyclisation in the peptide field. Obviously, in our case, a D-tripeptide reacts preferentially with an I,-tripeptide, and vice versa.Models for the conformation of cyclohexapeptides are discussed: that proposed by SCHWYZER (Fig.3)Is) allows construction of the optically active as well as of the meso-cyclohexapeptides on the same basic ring structure, and is supported by IR. data.