This proposal outlines a blueprint towards the development of a new catalytic strategy for chemical synthesis, wherein catalytic cascade processes are designed around the transformation of a common functional motif to a diversity of enantiopure natural product architectures, in a single step. The hypothesis behind the chemo-catalytic synthesis strategy involves the development of a catalytic enantioselective dearomatization (CED) process that directly converts flat aromatic molecules into complex asymmetric structures. The transformation involves a tandem process, comprising oxidative dearomatization and organocatalytic desymmetrization, generating highly functionalized, non-racemic architectures. The natural product targets structures of alkaloids, polyketide, steroid and terpene biosynthetic origin, and complex non-natural frameworks that may have interesting properties, as the basis for novel small-molecule libraries with untapped biological properties. The programme of research will focus on the exploitation and the development of the cascade ‘zipper-reaction’ concept, CED, wherein simple, linear molecules can be directly converted to complex enantiopure architectures that closely resemble the structures of bioactive natural products. The proposal will have four parts over the two-year period of the proposed Fellowship : the method development for the CED cascade process, the total synthesis of morphine and the development of novel scaffolds for drug discovery. The research outlined in this proposal is a representative part of a 'grand challenge' programme to provide a chemo-catalysis blueprint for synthesis that is inspired by the efficacy of biosynthesis.