Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction

• Published in: Nature chemistry Vol. 6; no. 6; pp. 484 - 491
• Main Authors: Woerly, Eric M., Roy, Jahnabi, Burke, Martin D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2014; Nature Publishing Group
• Subjects: 140/131; 639/638/549/977; Algorithms; Amino acids; Analytical Chemistry; Automation; Biochemistry; Biological Products - chemical synthesis; Carotenoids - chemical synthesis; Chemistry; Chemistry/Food Science; Glucosides - chemical synthesis; Inorganic Chemistry; Modularity; Molecular Structure; Natural products; Organic Chemistry; Physical Chemistry; Polyenes - chemistry; Polypeptides; Stereoisomerism; United States > US; Illinois
• ISSN: 1755-4330; 1755-4349; 1755-4349
• DOI: 10.1038/nchem.1947

The inherent modularity of polypeptides, oligonucleotides and oligosaccharides has been harnessed to achieve generalized synthesis platforms. Importantly, like these other targets, most small-molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled both the synthesis of a wide range of polyene frameworks that covered all of this natural-product chemical space and the first total syntheses of the polyene natural products asnipyrone B, physarigin A and neurosporaxanthin β- D -glucopyranoside. Collectively, these results suggest the potential for a more generalized approach to making small molecules in the laboratory. Polyene motifs are found in a large number of natural products. Now, by applying a general retrosynthetic algorithm, it has been shown that the polyene motifs found in >75% of these compounds can be synthesized using just 12 bifunctional haloalkenyl MIDA boronate building blocks and one coupling reaction.