Biosynthesis of Staurosporine: Incorporation of Glucose

Abstract

Previously, it was disclosed that tryptophan provides two units of the basic building blocks involved in the biosynthesis of the indolo[2,3-a]carbazole unit of staurosporine (1). In this paper we describe the incorporation of [1-13C]-d-glucose and [U-13C6]-d-glucose into staurosporine, through which it was established that the amino-sugar moiety is derived from glucose, based on the observation of the direct incorporation of uniformly labeled 13C glucose, and that glucose is converted via glycolysis and the shikimic acid pathway to tryptophan and hence into 1. Deuterium-labeled glucose derivatives, including [6-2H2]-d-glucose, [2-2H]-d-glucose, and [U-2H7]-d-glucose, were used to determine the biogenetic origin of the protons in staurosporine (1). From uniformly deuterium-labeled glucose up to seven deuterium atoms were incorporated into 1 according to EIMS. Probably, five protons were incorporated into the glycon moiety, and two protons into the aglycon unit based on an analysis of the 1H-NMR spectrum an...