Enantioselective Entry into Benzoxabicyclo[2.2.1]heptyl S stems via Enzymatic Desymmetrization: Toward Chiral Building Blocks for Lignan Synthesis

Abstract: The meso diacetate, 9, available in seven steps from piperonal, is efficiently desymmetrized with preferential cleavage of the R-arm-acetate under catalysis by porcine pancreatic lipase in 10 % DMSO-phosphate buffer, pH 8. The resulting monoacetate 12, a potentially useful chiral building block for the synthesis of derivatives of the Podophyllum lignans, is obtained in good chemical yield (66-83%) and in high optical yield (95 % ee) on a multigram scale.Copyright © 1996 Elsevier Science Ltd Semisynthetic derivatives of the aryl tetralin lignan (-)-podophyllotoxin (1), such as etoposide (2) 1 and teniposide (3), are important chemotherapeutic agents. Etoposide has displayed remarkable efficacy as a single agent in the treatment of small cell lung cancer, testicular cancer, Hodgkin's and non-Hodgkin's lymphoma, several leukemias and Kaposi's sarcoma (the tumor most closely associated with AIDS). 2-4 More recently, etoposide has been identified as a very good candidate for the treatment of life-threatening cytomegalovirus (CMV) infections. 5 6 3 1 (-)-Podophyllotoxin X=OMe Y = [