Development of a total synthesis of Myxovalargin A and derivatives ̶ investigations on transformations with polymer-supported Bisazidoiodate (I)

Abstract

The first part of this dissertation deals with the chemical total synthesis of peptide natural product Myxovalargin A, which was isolated from a culture supernatant of the myxobacterial strain Myxococcus fulvus, Mx f65, and first mentioned by name as early as 1981. It exhibits antibiotic activity against a wide range of GRAM-positive and GRAM-negative bacteria. However, the amino acid sequence with corresponding configurations obtained from feeding experiments at that time contrasts with the results of a recent gene cluster analysis. For this reason, both variants of myxovalargin were synthesized in this work by a combination of solid-phase and liquid-phase peptide chemistry. Mass spectrometric comparisons of the two synthesized myxovalargins with the natural product isolated from the bacterial supernatant confirmed unequivocally the stereochemistry postulated by the gene cluster analysis. Moreover, a synthetic approach for structurally simplified myxovalargin derivatives was investigated. The second part of this dissertation deals with chemical studies on polymer-bound bisazidoiodate (I), which exhibits the same chemical properties as iodoazide, but not its explosive character. Of particular importance here is the photochemically induced homolytic cleavage of iodine azide to release azide radicals, which provide the reactive species for the chemoselective oxidation of secondary alcohols in the presence of primary alcohols. In addition, a new reactivity of iodine azide toward phenols and ketones was explored, with the intermediate formation of hypoiodite being the key step in the oxidative azidation of phenols and ketones.