Practical Synthesis of Substituted Anthraquinones, Streamlined Synthesis of Trioxacarcins and Analogues, and Synthetic Studies toward LL-D49194alpha1
Nicolaou, Kyriacos Costa
Doctor of Philosophy
Chapter 1 of this thesis described the development of a novel variation of Hauser-Kraus annulation to construct o- or p-amino and methoxyphenolic athraquinones, which are common motif presented in natural products and designed molecules of industrial and medicinal importance. In this work, a series of o- or p-semiquinone aminals were designed, synthesized, and applied as useful building blocks to undergo Hauser-Kraus annulation with cyanophthalides to selectively deliver corresponding o- or p-amino and methoxyphenolic athraquinones upon careful tuning of substrates and reaction conditions. Chapter 2 presented the efforts to streamline the synthesis of naturally occurring trioxacarcins, antitumor antibiotics with intriguing structure, and their analogues. The postponed installation of oxidation states on the naphthol core of the advanced intermediate drastically promoted the efficacy of the synthesis, enabling the construction of several anthraquinone analogues, from which a novel cascade reaction leading to 2-chloroanthraquinone was discovered concomitantly. As a result, a couple of trioxacarcins and their analogues were synthesized deploying the developed strategy. Chapter 3 exhibited my efforts in developing new synthetic strategy for precedingly synthetically inaccessible trioxacarcin analogues and natural products from LL-D49194 family, which featured a glycosylated hemiacetal functionality The room-temperature stability of such an acyclic hemiacetal was identified and was successfully implemented into a glycosylation reaction. discussed before the synthetic potential of hemiacetal in our synthesis plan was demonstrated. After the fail attempts to construct advanced intermediates from a formal [4+2]cycloaddition and surrogated Baylis-Hillman reaction for the previously adapted epoxyketone rearrangement, a new synthetic strategy was brought up and is currently under investigation for the construction of trioxacarcin core structure from a previously rarely used feed stock of D-tagatose.
anthraquinone; semiquinone aminal; Hauser-Kraus annulation; trioxacarcin; anticancer antibiotics; More... DNA leision; spiral epoxide; natural products; epoxy ketone rearrangement; 2,7‐dioxabicyclo[2.2.1]heptane; bicyclic acetal; Baylis-Hillman reaction; polyketide; LL-D49194; D-tagatose; 3-furanone Less...