Novel synthetic routes towards polycyclic alkaloids and tetracycline ring systems

Novel and complementary routes for the selective preparation of either the 2,11 b-cis (B) or trans (C) series of functionalised benzo[α]quinolizidines have been developed and reported in close collaboration with the Bosch group. The common aromatic core, chiral p-aminoalcohol (A), allows access to either (B) or (C) via judicious choice of substrate sub-structure for lactamisation. The key cyclisation step in both instances involves the attack of a pendent aromatic nucleophile onto an N-acyliminium intermediate. [Illustration omitted.] Also described in this thesis is the first asymmetric synthesis of the dodecahydrobenz[α]indolo[3,2-h]quinolizine ring system (E), a common sub-structure of several bioactive indole alkaloids. Our approach furnishes the pentacyclic indole core of the manadomanzamine skeleton with complete control over the relative and absolute stereochemistries at the three contiguous chiral centres at positions 1, 10 and 24. [Illustration omitted.] The source of indole and chiral auxiliary, (S)-tryptophanol (D) has also been elaborated towards a functionalised analogue (F) with a synthetic 'handle' for further derivatisation. Synthetic routes towards the tetracycline class of compounds have also been investigated.