Asymmetric Total Synthesis of Cephanolide A

Abstract

The first asymmetric total synthesis of cephanolide A, a complex hexacyclic C 18 dinorditerpenoid from cephalotaxus sinensis, was achieved. The synthesis features a convergent strategy, which provides a flexible approach to prepare the biogenetically cephalotaxus diterpenoids and structurally related derivatives for biological studies. A mild intramolecular Prins cyclization was developed to construct the central hexahydrofluorenol skeleton (A-B-C ring), which relies on the originally proposed hydroacylation strategy. A remote hydroxy group directed hydrogenation was applied to stereospecifically reduce the tetra-substituted enone unit. A sequence of ring forming steps, including lactonization, cation mediated etherification and Friedel-Crafts cyclization, was efficiently utilized to forge the cage-like skeleton.

De Novo Diastereoselective Synthesis of 1-Hydroxyl Allogibberic Methyl Ester en Route to Diverse Bioactive Molecules

“…Then, the α-hydroxyl ketone motif was disconnected to an aldehyde and a cyclic ketone in intermediate 11 by a strategic transannular pinacol coupling reaction . Next, the central cyclopentenone in 11 bearing an all-carbon quaternary center could hopefully be constructed through a Prins cyclization reaction of an aldehyde with an endocyclic alkene in 12 , which in turn would be accessed from a Suzuki–Miyaura coupling reaction between phenyl boronate 13 and alkenyl triflate 14 . Finally, 13 and 14 were believed to be readily available because 13 could be made from the known compound 15 through Miyaura boration while compound 14 is known in literature …”