Atropo-enantioselective total

An efficient atropo-enantioselective total synthesis of the axially chiral bicoumarin (+)-isokotanin was accomplished by J. Bringmann and co-workers.The key steps in this synthetic approach were the formation of a configurationally stable seven-membered biaryl lactone by the Cannizzaro reaction of the corresponding biaryl dialdehyde followed by a kinetic resolution by atroposelective ring cleavage. 

The first atropo-enantioselective total synthesis of a phenylanthraquinone natural product (Af)-knipholone was reported by G. Bringmann et al. In the late stages of the synthesis, an acetyl group had to be introduced under mild conditions. The advanced substituted anthraquinone intermediate was first deprotected with TiCU and then acylated with AC2O in the presence of TiCU. A spontaneous Fries-rearrangement took place to afford the ortho-acylated product in high yield. The natural product was obtained by a mono O-demethylation at C6 with AIBrs. 

The AB-biaryl fragment of vancomycin, a glycopeptide antibiotic, was prepared on the basis of this methodology. Furthermore, the method was also applied to the synthesis of natural products without Ci-sustituents next to the biaryl axis such as dioncophylline C or korupensamine B. One of the most recent applications of the concept in natural product synthesis was the first and atropo-enantioselective total synthesis of (+ )-knipholone, an antimalarial phenylanthraquinone. Against the steric hindrance by the C-10 keto function. 

---