Part I: The total synthesis of (+/-)-securinine and (+/-)-allosecurinine and synthetic strategies for a second generation synthesis of the securinega alkaloids and Part II: The use of (+)-K252a in the semi-synthesis of indolocarbazole natural products and

In part I, the total syntheses of (+/-)-securinine ((+/-)- 1.001) and (+/-)-allosecurinine ((+/-)-1.003) are described. The syntheses feature the use of a Rh-initiated O--H insertion/Claisen rearrangement/1,2-allyl migration, which would allow for an enantioselective synthesis when an enantioenriched allylic alcohol (ie: (+)-1.137) is used. Three more steps generates the common intermediate imine 1.144, which upon reduction gives a pair of diastereomers. Protection of the free amine and a second reduction gives 1.146a and 1.146b, which were advanced to (+/-)-1.003 and (+/-)- 1.001 respectively. Additional investigations into improving the endgame and devising a more streamlined synthesis were conducted. This focused on reducing the number of oxidation state changes at C13.;Part II of this dissertation details efforts to employ (+)-K252a ( 2.016) as a starting material for the synthesis of potential Hox-A14 inhibitors based on the indolocarbazole scaffold. It also covers the development of a novel method of selectively protecting the amide of 1.016 with a DMB group. This protected analog was employed as the starting material for a potential synthesis of the recently isolated indolocarbazoles Streptocarbazole A (2.019) and B (2.020). The proposed route to these compounds is via C--N bond migration on ketone 2.138 or dimethylketal 2.158. Substrates 2.138 and 2.158 have been synthesized. Preliminary investigations into conditions for the desired rearrangement have been conducted.