A New Ribose Nucleoside from Neurospora: "Orotidine"

A series of investigations using mutants of the fungus Neurospora has provided ample evidence that the pyrimidine orotic acid has a significant role in the biological synthesis of the ribose nucleosides uridine and cytidine [1-4]. By use of isotopically labeled orotic acid several investigators [5-8] have recently demonstrated that a similar conclusion may be drawn concerning a function of this pyrimidine in the biosynthesis of nucleic acids in animal tissues. In addition, an apparently more specialized biochemical activity of orotic acid has been shown [9-12] for the organism L. bulgaricus. Thus, it now seems evident that this pyrimidine is an important substance in biological systems in general. However, results of the earlier work with Neurospora mutants in this laboratory suggested that the principal pathway of biosynthesis of uridine in the mold consists of the building of the pyrimidine component stepwise onto the carbohydrate rather than of a direct coupling of ribose and uracil. As a consequence of this hypothesis, several attempts have been made to synthesize glycosides and especially a ribofuranoside of orotic acid. None of these experiments yielded a carbohydrate derivative of this pyrimidine [13]. However, it now appears that the desired product has been obtained by isolation from one of the uridine-requiring mutants of Neurospora (strain 36601). The present report is concerned with this isolation and with some of the properties of the crystalline cyclohexylamine salt of the orotic acid riboside