Guided by the insecticidal activity against the agricultural pest insect Pectinophora gossypiella, Kubo and Kim isolated clitocine (1a) [1], along with adenosine, from Clitocybe inversa, a medium-sized, buff-colored mushroom found in western North America. The NMR spectral data for clitocine was found to be very similar to that of adenosine, with the exception of the absence of the C-8 carbon peak of adenosine, while the low chemical shift of the 4-NH proton suggested strong hydrogen bonding between the 5-NO 2 and 4-NH groups. Later, Moss and coworkers [2] confirmed its structure through X-ray crystallographic analysis: as postulated earlier by Kubo et al., the entire aglycone moiety resembles a tricyclic ring system as a result of the hydrogen bonding between the 4-NH and 6-NH protons and the NO 2 group.
SynthesisThe interesting biological activity of clitocine, together with its biogenetically close relationship to adenosine, triggered an immediate attempt to synthesize the molecule de novo. Two years after its initial isolation, two independent syntheses have now been completed. The first synthesis [3] is based upon the condensation of 2,3,5-tribenzoylribofuranosylamine (2) with 4,6-dichloro-5-nitropyrimidine (3) in the presence of a base to give a mixture of the a-and b-anomers in a 7 : 1 ratio (Scheme 22.1), although the yield (19%) is relatively poor. Deprotection of the benzoate group of 4 using a methanolic ammonia solution produced clitocine with a 71% yield. In order to improve the efficiency and reproducibility of the coupling reaction, an acetonideprotected amino sugar (5) was employed for the coupling reaction with 4-chloro-5-Modified Nucleosides: in Biochemistry, Biotechnology and Medicine. Edited by Piet Herdewijn