Biosynthesis of Staurosporine: Incorporation of Glucose

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- 13 C]- d -glucose and [U- 13 C 6 ]- 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 13 C 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- 2 H 2 ]- d -glucose, [2- 2 H]- d -glucose, and [U- 2 H 7 ]- 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 1 H-NMR spectrum and the fragment peaks in the EIMS.