Stereospecific synthesis of azabeyerene: An aza analog of the beyeranyl carbocation and a potential inhibitor of diterpene synthases

ORGN 436

Arnab Roy, arnabroy@uiuc.edu, Frank G. Roberts, and Robert M. Coates, coates@scs.uiuc.edu. Department of Chemistry, University of Illinois at Urbana-Champaign, Roger Adams Laboratory, 600 S Mathews Avenue, Urbana, IL 61801
The ent-beyeranyl carbocation 1 is a branch point intermediate in the biogenesis of a large family of tetra and pentacyclic diterpenoids. The aza analog 4 is a potential transition state inhibitor for diterpene synthases involved in the biosynthesis of these natural products as outlined in Scheme 1. We have developed an efficient synthesis of azabeyerene 4 from isosteviol 2 utilizing a Beckman fragmentation and Hg(II)-mediated stereospecific cyclization of unsaturated amine 3 as key steps. Pb(OAc)4 oxidation of 3 provides azatrachylobane 5 whose single crystal x-ray structure has been solved as a picrate salt and compared with the x-ray structure of a natural trachylobane ester to study its inhibition activity. Thermodynamically and kinetically controlled aziridine ring openings of 5 have also been studied and hold promise for the construction of other tetracyclic aza analogs.

 

Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005