Asymmetric Total Synthesis of (+)‐Mannolide C

Abstract

(+)‐Mannolide C is a complex hexacyclic C20 cephalotane‐type diterpenoid featuring a highly strained 7/6/6/5 tetracyclic core containing eight consecutive stereocenters and two bridging lactones. The first asymmetric total synthesis of (+)‐mannolide C has been accomplished by lipase‐mediated resolution, Ru‐complex‐catalyzed double ring‐closing metathesis (RCM) reactions, NiII‐catalyzed diastereoselective Michael addition, and MnIII‐catalyzed allylic oxidation as the key transformations.

Cephalotane‐Type Norditerpenoids from Cephalotaxus fortunei var. alpina

“…70 derivatives comprising six types of rearranged carbon skeletons were reported successively, [ 9 ] some of which exhibited potent anti‐inflammatory activities [ 5 ] and inhibition of the NF‐κB signaling pathway, [ 5,10 ] and have garnered a fair amount of attention from the synthetic community. [ 11‐17 ] As part of our continuing search for structurally intriguing and/or biologically significant cephalotane diterpenoids/norditerpenoids from Cephalotaxus species, [ 8,10,18‐21 ] nine new cephalotane‐type norditerpenoids ( 1 — 9 ) and two known analogues ( 10 and 11 ) (Figure 1) were isolated from the seeds of C. fortunei var. alpina .…”

Total syntheses of strained polycyclic terpenes

“…Total synthesis of terpenoids is a highly dynamic field with dozens of targets both classical and newly isolated being synthesised every year. In order to put the small ring containing terpenoids in a broader context, Chart 1 summarises a number of polycyclic terpenes 2–36 prepared over the last 5 years, highlighting key reactions, utilised to form the corresponding ring systems. This chart is intended to give a reader an overview of modern approaches to construction of polycyclic carbon architectures in modern synthetic chemistry.…”

Construction of Tetracyclic Core Skeleton of Cephalotaxus Diterpenoids through Diastereoselective Pauson‐Khand Reaction

“…[6] Notably, Zhai and coworkers recently reported the asymmetric total synthesis of mannolide C through a double ring-closing metathesis strategy. [7] Zhao and coworkers reported the development of a palladium-catalyzed cascade cyclization and total syntheses of cephanolides B and C. [8] Gao and coworkers accomplished the asymmetric total syntheses of cephanolides A [9a] and B [9b] on the basis of a mild intramolecular Prins cyclization. Sarpong and coworkers reported a divergent synthetic approach to cephanolides AÀ D through an intramolecular inverse-demand Diels-Alder reaction strategy.…”

“…Zhai and coworkers achieved the asymmetric total synthesis of harringtonolide with the employment of rhodium‐catalyzed intramolecular [3+2] cycloaddition [6] . Notably, Zhai and coworkers recently reported the asymmetric total synthesis of mannolide C through a double ring‐closing metathesis strategy [7] . Zhao and coworkers reported the development of a palladium‐catalyzed cascade cyclization and total syntheses of cephanolides B and C [8] .…”