Direct and Short Construction of the ACDE Ring System of Daphenylline

Abstract

Daphenylline, a novel daphniphyllum alkaloid, boasts a fused and bridging ring system coupled with six stereogenic centers. Here we present a direct and short construction of the ACDE ring system of daphenylline from the known 3-(2-bromophenyl)propanal in 10 steps and 17 % overall yield. The synthesis features an iron(III)-catalyzed aza-Cope-Mannich reaction, a self-terminating 6-exo-trig aryl radical-alkene cyclization and an intramolecular Friedel-Crafts acylation.

Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline

“…Oxidative cleavage of the furan ring of 15 with PCC gave acetate 16 in aq uantitative yield. [8] In summary,wehave completed the first total synthesis of (À)-daphnilongeranin B( 3)a nd ab ioinspired total synthesis of (À)-daphenylline (4). An intramolecular aldol condensation completed the construction of the daphenylline core to afford compound 18 in 76 %yield by the treatment of 17 with aqueous NaOH in MeOH/brine (1:1) at 80 8 8C.…”

“…From as tructural point of view,b oth 3 and 4 contain aseries of synthetically challenging structural features found in many calyciphylline At ype alkaloids,a nd they share ac ongested bowl-like hexacyclic substructure.T he [6.6.5.7.5.5] backbone of daphnilongeranin Bp ossesses seven stereogenic centers,f our of which are contiguous, including two vicinal quaternary centers.U nique to 4, however, is the highly fused hexacyclic [6.6.5.7.6.5] core containing ap eculiar tetrasubstituted benzene ring and six stereogenic centers;i ti st he only member of the Daphniphyllum alkaloids that contains an aromatic ring. [3][4][5] So far, there have been only two total syntheses of (À)-daphenylline (4), reported by the research groups of Li [5b] and Fukuyama/ Yokoshima. [3][4][5] So far, there have been only two total syntheses of (À)-daphenylline (4), reported by the research groups of Li [5b] and Fukuyama/ Yokoshima.…”

Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline

“…The complex polycyclic molecular architectures of 3 and 4 thus posed as ignificant synthetic challenge. [3][4][5] So far, there have been only two total syntheses of (À)-daphenylline (4), reported by the research groups of Li [5b] and Fukuyama/ Yokoshima. [5c] However,t he total synthesis of daphnilongeranin Bh as not been accomplished to date.…”

Total Syntheses of Daphenylline, Daphnipaxianine A, and Himalenine D

“…[11] Theb iogenesis of Daphniphyllum alkaloids offers important information for developing synthetic routes to these molecules; [1a] for example, Heathcock and co-workers developed an elegant biomimetic polycyclization cascade. [4] During our previous synthesis of daphenylline (1, Figure 1), [6,12] we were intrigued by abiosynthetic hypothesis for the formation of this alkaloid from acharacteristic calyciphylline Atype [1c] Daphniphyllum alkaloid, daphenilongeranin C [13] (2), proposed by Hao and coworkers,w ho isolated 1. [14] Am inor modification of their proposal is illustrated in Figure 1.…”