Novel synthetic applications of N-acyliminium ions toward β-turn mimetics and naturally occurring alkaloids

The asymmetric approach to a range of substituted indolizidine templates (3) from nonracemic substrates (1), based around the development of a diastereoselective N-acyliminium cyclisation strategy, is well established within our group. [Illustration omitted.] The application of this novel methodology in target synthesis has been demonstrated by the manipulation of chiral building blocks such as (3). The removal of functional groups has allowed assess to therapeutically active natural products including (+)-crispine A (4) and (+)-harmicine (5), whilst the exploitation of their existing functionality has been utilized to form complex β-turn peptide mimics, such as (6). [Illustration omitted.] The scope of this methodology has been extended with the novel N-acyliminium cyclisation/retro Diels–Alder tandem synthesis of the complex pentacyclic template (10), from the lactam precursor (9). Analogues of such templates are used as key intermediates in the synthesis of the Cephalotaxus alkaloids.