Chemistry of Acronycine, XI. Rearrangement of Dihydronoracronycine to Dihydroisonoracronycine-Mechanistic Studies

Abstract

The rearrangement of dihydronoracronycine (3) to dihydroisonoracronycine (4) proceeds by way of an intermolecular reaction rather than an intramolecular reaction as had originally been supposed. Deuterium-labeling studies showed the incorporation of deuterium at C3, C12, and the geminal methyl positions of dihydroisonoracronycine (4). Because no reaction occurred when the bisnor derivative was treated in the same manner as 3, it appears that the chromene geminal methyl groups are important for the rearrangement to occur.

Structural diversity and biological relevance of benzenoid and atypical ansamycins and their congeners

“…In our structural division of ansamycins, the third group of atypical macrolactams appears as a consequence of developing mutasynthetic and combined approaches. Furthermore, in an addition to the earlier classification, 27 we propose several subgroups of benzenoid ansamycins represented by a specific core type, namely: benzene, dibenzene, cyclohexa-2-enone, cyclohexa-2,5-dienone, benzoquinone or atypical ( e.g. alicyclic or heterocyclic) and containing ansa chains of different lengths (Fig.…”

“…Funayama and Cordell divided ansamycins into two main groups regarding the type of the core and the length of the carbon ansa chain. 27 Such an classification of ansamycins is in general reasonable but these two groups can be also more precisely divided further in view of the structure of the core, as shown in Fig. 3.…”

“…Many published investigations have been devoted to structural studies, quantitative or qualitative detection, biological activity, biosynthesis and semisynthetic modifications of these natural products, and the results of these investigations have been very interesting, both from biological and chemical points of view. 7–30 Newly discovered benzenoid ansamycin scaffolds and their modifications as potential attractive toward pharmaceutical and medical applications have stimulated detailed multidisciplinary studies that have aimed to determine the relationship between structure and useful biological effect. However, these studies are not trivial due to complexity of the structure and the different mechanisms of action of ansamycins.…”

“…Funayama and Cordell, focused on providing an overview of the classification and biosynthesis of ansamycins (benzenoid and naphthalenoid) by the year 2000. 27 Reviews concerning geldanamycin and ansamitocins, important members of benzenoid ansamycins, were earlier published by: Floss et al (biosynthesis), 23,31 Kirschning et al (ansamycins and their modifications targeting Hsp90) 32,33 and Moody et al (geldanamycin anticancer properties) 7 by the year 2013. Structural, biosynthetic, biological and analytical aspects of benzenoid ansamycins were also discussed in reviews from the years 1972 and 2010.…”

“…Structural, biosynthetic, biological and analytical aspects of benzenoid ansamycins were also discussed in reviews from the years 1972 and 2010. 15,23,24,27,29–31,34–36 Benzenoid and atypical ansamycins are being investigated at an increasing pace due to the new abilities to extract them from natural sources as well as due to the rapidly progressing modifications of these compounds via semisynthetic and mutasynthetic approaches or their combinations, in aim to optimize their biological properties. The review of the recent advances in the field of natural benzenoid and atypical ansamycins and their modifications is needed to highlight possible challenges concerning their biological applications.…”