Structural Diversity from the Transannular Cyclizations of Natural Germacrone and Epoxy Derivatives: A Theoretical-Experimental Study

• Published in: Chemistry : a European journal Vol. 19; no. 21; pp. 6598 - 6612
• Main Authors: Pérez Morales, M. Carmen, Catalán, Julieta V., Domingo, Victoriano, Jaraíz, Martín, Herrador, M. Mar, Quílez del Moral, José F., López-Pérez, José-Luis, Barrero, Alejandro F.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17-05-2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Biocompatibility; Biosynthesis; Chemistry; Computation; conformational analysis; Cyclization; density functional calculations; Derivatives; Divergence; Epoxy Compounds - chemistry; Lewis acid; Lewis Acids - chemistry; Mathematical analysis; Models, Theoretical; Molecular Structure; ring closure; Sesquiterpenes, Germacrane - chemical synthesis; Sesquiterpenes, Germacrane - chemistry; terpenes
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201300662

Treatment of germacrone (1) with different electrophiles, and of its epoxy derivatives germacrone‐4,5‐epoxide (2), germacrone‐1,10‐epoxide (3) and isogermacrone‐4,5‐epoxide (4) with Brönsted/Lewis acids and TiIII, gives rise to a great structural diversity. Thus, by using a maximum of two steps, the production of more than 40 compounds corresponding to 14 skeletons is described. Computational calculations rationalizing the structural divergence produced are also described. Finally, since some of the compounds generated are bioactive natural sesquiterpenes, the mechanisms of formation of these substances will provide new insights in their biosynthesis.
Diversity rules: More than 40 structures, possessing 14 different molecular skeletons, were generated from naturally available germacrone in only two or three steps (see scheme). Computational calculations aimed to rationalize the structural divergence produced were performed. These chemical studies could also shed light on the biosynthesis of some of the natural sesquiterpenes synthesized.