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Open Access Publications from the University of California

Synthesis of Isotopically Labeled Co-Enzyme to Probe the Active Site of Tryptophan synthase/ New Synthetic Approach to Tetrahydrocannabinol Analogs

  • Author(s): Bastin, Baback
  • Advisor(s): Marsella, Michael
  • et al.

Identifying enzyme mechanisms at proton level resolution is the ultimate goal of enzymology. Traditional enzyme mechanistic studies infer protonation states from x-ray crystal structure and optical spectroscopy. This thesis reports work towards the first synergistic combination of x-ray crystallography, computational chemistry, synthetic organic chemistry and solid-state NMR to fully elucidate, at proton level resolution, the full three-dimensional structure of the catalytic site for Tryptophan synthase during active catalysis. Specifically, this thesis describes solutions to the synthetic challenges of introducing site-specific isotopic labels inside the cofactor Pyridoxal-5’-Phosphate (PLP) and highlights a synthetic route that is consistently more cost-effective and higher yielding than previous efforts.

The second project presented focuses on efforts towards the synthesis of cannabinoids, cannabidiol (CBD) and tetrahydrocannabinol (THC). Presently, cannabinoids have emerged as compounds of interest for a variety of pharmacologic indications. Although stereochemically simple compounds, economical syntheses of enantiopure cannabinoids remain elusive. Strategies to address facile syntheses of THC and CBD, as well as their analogs, will be presented.

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