TY - JOUR

T1 - Synthetic Studies Probing Elansolid Biosynthesis

T2 - A para-Quinone-Methide-Triggered Intramolecular Diels–Alder Reaction

AU - Wang, Liangliang

AU - Candito, David

AU - Dräger, Gerald

AU - Kirschning, Andreas

N1 - Funding information: The work was funded in part by the Deutsche Forschungsge-meinschaft (Cluster of Excellence REBIRTH; “From Regenerative Biology to Reconstructive Therapy” EXC 62). D. C. thanks the Alexander-von-Humboldt Foundation for a postdoctoral scholarship.

PY - 2017/8/28

Y1 - 2017/8/28

N2 - The elansolids A1/A2 and B1–B3 are secondary metabolites formed by the gliding bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. It has been proposed that the biosynthesis of the tetrahydroindane unit involves an intramolecular Diels–Alder cycloaddition (IMDA). To study the biosynthetic proposal, the influence of an oxygen functionality at C-20, the regiochemistry of the allylic alcohol precursor, and the nature of the phenol group were investigated. The oxygen functionality at C-20 has a profound effect on the outcome of this reaction, resulting in a Prins-type reaction cascade initiated by a p-quinone methide intermediate, and leading to an unexpected cycloadduct. The corresponding 20-deoxy precursor, as suggested for the naturally occurring IMDA precursor smoothly yields the desired IMDA product as a mixture of two endo products. These results support the hypothesis that nature probably uses an intramolecular Diels–Alder cycloaddition to generate the bicyclic core of the elansolids starting from a 20-deoxygenated precursor.

AB - The elansolids A1/A2 and B1–B3 are secondary metabolites formed by the gliding bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. It has been proposed that the biosynthesis of the tetrahydroindane unit involves an intramolecular Diels–Alder cycloaddition (IMDA). To study the biosynthetic proposal, the influence of an oxygen functionality at C-20, the regiochemistry of the allylic alcohol precursor, and the nature of the phenol group were investigated. The oxygen functionality at C-20 has a profound effect on the outcome of this reaction, resulting in a Prins-type reaction cascade initiated by a p-quinone methide intermediate, and leading to an unexpected cycloadduct. The corresponding 20-deoxy precursor, as suggested for the naturally occurring IMDA precursor smoothly yields the desired IMDA product as a mixture of two endo products. These results support the hypothesis that nature probably uses an intramolecular Diels–Alder cycloaddition to generate the bicyclic core of the elansolids starting from a 20-deoxygenated precursor.

KW - Biomimetic synthesis

KW - Cyclization

KW - Cycloaddition

KW - Diels–Alder reaction

KW - Natural products

KW - Prins reaction

UR - http://www.scopus.com/inward/record.url?scp=85030750468&partnerID=8YFLogxK

U2 - 10.1002/ejoc.201701125

DO - 10.1002/ejoc.201701125

M3 - Article

AN - SCOPUS:85030750468

VL - 2017

SP - 5582

EP - 5591

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

SN - 1434-193X

IS - 37

ER -