Asymmetric synthesis of penostatins A-D from L-ascorbic acid.

The first asymmetric synthesis of (-)-penostatins B and D and the practical synthesis of (+)-penostatins A and C have been accomplished through a flexible strategy. The features of the synthesis are a BF 3 ·OEt 2 -mediated Diels-Alder reaction of chiral dienophiles and methylcyclopentadienes with high chemo-, regio-, and stereoselectivity, followed by ozonolysis to install the common trisubstituted cyclopentane intermediate, and a hetero-Diels-Alder reaction with easily tunable facial selectivity, followed by sulfonate elimination to construct both enantiomeric tricyclic systems for penostatins A/C and B/D, respectively.