Academic Commons

Theses Doctoral

Combined Biosynthetic and Synthetic Production of Valuable Molecules: A Hybrid Approach to Vitamin E and Novel Ambroxan Derivatives

Adanve, Bertrand Tankpinou

Synthetic chemistry has played a pivotal role in the evolution of modern life. More recently, the emerging field of synthetic biology holds the promise to bring about a paradigm shift with designer microbes to renewably synthesize complex molecules in a fraction of the time and cost. Still, given synthetic chemistry’s superior parsing powers to access a greater number of unnatural end products and nature’s virtuosity at stitching a staggering palette of carbon frameworks with ease, a hybrid approach that leverages the respective strengths of the two fields could prove advantageous for the efficient production of valuable natural molecules and their analogs.
In a first demonstration of the hybrid approach where the biosynthesized intermediate is not part of the target molecule’s biosynthetic pathway, we engineered E. coli to produce Z,E-farnesol, which we subsequently transformed into a library of novel analogs of the commercially important amber fragrance Ambrox®, including the first synthetic patchouli scent. In a second demonstration of the hybrid approach, we produced the valuable tocotrienols (vitamin E) from yeast-produced geranylgeraniol in a single step C–C coupling with concomitant regioselective cycloetherification of the most proximal vinyl of the polyene, the first such process of its kind. The novel acid catalyst system that allowed for this unique regioselective cyclization holds promise as an asymmetric proton transfer tool and could open the door to facile asymmetric synthesis of vitamin E and other molecules.

Files

  • thumnail for Adanve_columbia_0054D_12875.pdf Adanve_columbia_0054D_12875.pdf binary/octet-stream 15 MB Download File

More About This Work

Academic Units
Chemistry
Thesis Advisors
Cornish, Virginia W.
Snyder, Scott A.
Degree
Ph.D., Columbia University
Published Here
August 11, 2015
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.