Researchers Transform Platform Chemicals into Natural Products
Researchers at the Center for Biorenewable Chemicals (CBiRC), an NSF-funded Engineering Research Center (ERC) headquartered at Iowa State University (ISU), transformed an ideal platform molecule known as TAL (triacetic acid lactone) into diverse natural products using one- or two-step sequences. For example, pogostone, a natural product of interest because of its antimicrobial, antifungal, and anti-inflammatory activity, can be generated from TAL in one step with 96% yield; the best previously reported synthesis of pogostone gave only 5% overall yield.
Upgrading TAL to produce a variety of commercial products demonstrates the versatility of the platform-chemical approach. CBiRC researchers have generated unsaturated acids, 3-alkyl pyrenes, and pyrone-containing natural products directly from TAL. Because many of the natural products are present in plants in low natural abundance, these synthesis routes represent the best source of materials for systematic biological evaluation.
TAL (see figure) is an ideal platform molecule for the synthesis of an array of materials, including bioactive natural products and specialty chemicals. This work sets the stage for complex three-component condensations of TAL that propagate molecular diversity even more rapidly.
Understanding the reactivity of TAL is necessary to realize the full potential of this platform molecule and ultimately to incorporate its reactivity patterns into a computational framework. Accordingly, TAL has been the focus of bio-catalysis advances by companion CBiRC research activities.
TAL contains multiple nucleophilic and electrophilic sites. Acylation of TAL occurs selectively at C-3. In contrast, alkylation of the mono-anion of TAL occurs on the oxygen atom at C-4 and alkylation of the dianion of TAL occurs at the methyl group at C-6.
Analogs of pogostone are readily generated by acylation with acids. CBiRC researchers have found that some of chemically-generated analogs are metabolites in the plant that makes pogostone.