Abstract:
This thesis describes synthetic studies towards two natural products: bisindigotin (92) isolated from the leaves of Isatis indigotica,1 and strobilanthosides A and B (87 and 88) isolated from the aerial parts of Strobilanthes cusia (Nees) Kuntze (Baphicacanthus cusia (Nees) Bremek).2 Attempts towards bisindigotin (92) focussed on five distinct synthetic routes. Three synthetic approaches investigated the oxidative homo-coupling of indigo-derived substrates 108, 112 and 135 to access tetraindole structures with pre-installed C3-oxygens. During these studies several novel intramolecular rearrangements occurred, triggered by acid- or base-induced conditions resulting in new polycyclic heteroaromatic compounds 120, 121, 124, 136, 138, 139 and 141. A fourth strategy explored the dehydrogenation of tetraindole 109 followed by hydrolysis, which resulted in cyclised compound 149. The fifth approach focussed on accessing tetraindole 153 from the indigo-derived 151 followed by a C3-oxidation, however, this approach was not viable. A proposed biosynthesis suggests the structure of bisindigotin (92) may have been misassigned. Synthetic studies towards strobilanthosides A and B (87 and 88) focussed on a bioinspired annulation of dehydroindigo (67) and substituted phenols (180 – 186) in the presence of pyridine. This resulted in the formation of several bis-spirocyclic 2,2ʹ-bis(indolin-3-one) compounds 179, 187, 189 and 195 possessing the core scaffold of 87 and 88. In the absence of pyridine the reaction of 67 with tri-substituted phenols formed N-substituted indigos 192 and 194, suggesting the annulation is base-dependant. This observation was highlighted in the reaction of 2-methoxyphenol (184) with 67, forming 189 in the presence of pyridine and 193 in its absence. Based on these observations it was suspected the proposed bioinspired annulation of dehydroindigo (67) and verbascoside (89) may not produce the desired natural products with the correct regiochemistry. A revised synthetic strategy was proposed based on a plausible alternative biosynthesis.