Biosynthesis and Chemical Synthesis of Presilphiperfolanol Natural Products

• Published in: Angewandte Chemie International Edition Vol. 53; no. 21; pp. 5248 - 5260
• Main Authors: Hong, Allen Y., Stoltz, Brian M.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 19.05.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Biochemistry; Biological Products - chemical synthesis; Biological Products - metabolism; Biological Products - pharmacology; Biosynthesis; Cyclization; Enzymes - metabolism; Fungi - drug effects; Natural products; Organic chemistry; Origins; Precursors; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Sesquiterpenes - metabolism; Sesquiterpenes - pharmacology; Stereoisomerism; Strategy; structure elucidation; Synthesis; Terpenes; Terpenes - chemistry; terpenoids; total synthesis; natural products; terpenoids; structure elucidation; total synthesis; biosynthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201309494

Presilphiperfolanols constitute a family of biosynthetically important sesquiterpenes which can rearrange to diverse sesquiterpenoid skeletons. While the origin of these natural products can be traced to simple linear terpene precursors, the details of the enzymatic cyclization mechanism that forms the stereochemically dense tricyclic skeleton has required extensive biochemical, computational, and synthetic investigation. Parallel efforts to prepare the unique and intriguing structures of these compounds by total synthesis have also inspired novel strategies, thus resulting in four synthetic approaches and two completed syntheses. While the biosynthesis and chemical synthesis studies performed to date have provided much insight into the role and properties of these molecules, emerging questions regarding the biosynthesis of newer members of the family and subtle details of rearrangement mechanisms have yet to be explored. All in the family: The presilphiperfolane skeleton is an important intermediate in the diverging biosynthetic pathways leading to numerous sesquiterpene natural products. Research in natural products, biosynthetic, and computational chemistry has provided much insight into the major skeletal rearrangement mechanisms. Advances in synthetic organic chemistry have enabled access to several members of the presilphiperfolanol family by total synthesis and contributed to current understanding.