Finding activity through rigidity: syntheses of natural products containing tricyclic bridgehead carbon centers

Abstract

This review summarizes the syntheses of ten representative families of natural products that contain tricyclic bridgehead carbon centers (TBCCs). We organize the approaches around the five strategies shown to aid future synthetic endeavors.

A Photoinduced Radical Cascade Cyclization for the Synthesis of Angularly Fused Tricyclic Compounds

“…In addition to exhibiting a good substrate scope, this reaction overcomes the limitation of Prakash and Mohanakrishnan’s method by successfully synthesizing the substrate that was previously deemed incompatible. Moreover, it accomplishes the popular 5/5/5 angularly fused ring systems, which were not synthesized in the previous works of Prakash and Mohanakrishnan . and Sha et al This remarkable diversity in ring systems broadens the scope and potential applications of our developed methodology. , …”

“…Last year, we demonstrated the merit of PET-mediated enol silyl ethers in the divergent synthesis of a range of bridged and angularly fused tricyclic skeletons under varying additives and silyl protecting groups (Scheme a). , Utilizing the synthesized bicyclo[3.2.1]­octane as a key intermediate, we accomplished the first total synthesis of C20 oxygenated ent -kauranoid sculponin U. , For angularly fused tricyclic frameworks, we hypothesize that, by swapping the functional groups of olefins and alkynes in the substrates, the resulting double bond in the products would undergo a shift from an exocyclic to an inner cyclic configuration. Furthermore, we speculate that by incorporating double alkyne functional groups into the substrate, a more versatile tricyclic fused ring featuring a conjugated diene moiety could potentially be synthesized.…”

Concise Total Synthesis of (−)-Bipolarolide D

“…The A ring, being fully functionalized, contributes further to the compound’s intricate structure. While this compound’s unique structural features and biological properties of the ophiobolin family suggest potential avenues for future pharmacological research, − the scarcity of the source of 1 restricts in-depth research on its biological activity. Recently, the first total syntheses of its congeners, bipolarolides A and B, have been accomplished by the Jia group .…”

Asymmetric Construction of the Core of C6, C7-Epoxy Daphnane Diterpenoid Orthoesters

“…Compared to active synthetic studies and total syntheses of the structurally and biogenetically related tigliane and rhamnofolane diterpenoids, ,, fewer research groups are involved in the syntheses of DDOs. − So far, the groups of Wender, Inoue, and Maimone have completed successful total syntheses of DDOs, focusing on resiniferatoxin without a C 6 , C 7 -epoxy moiety (Scheme ). In 2011, the Wender group reported their synthesis of C 6 , C 7 -epoxy DDOs, albeit as a C 6 , C 7 -epimer of yuanhuapin, in the 41 longest linear steps .…”