Synthesis of aryltetralin type 2-azalignans using Schollkopf's bislactim-ether methodology

Synthesis of (1S,3R)-2-aza-4-deoxypodophyllotoxin has been accomplished in 6 steps using Schollkopf's bislactim-ether methodology in 12% total yield. Bislactim-ether, which was originally prepared from commercially available L -valine and glycine, was used as the starting material. Our synthetic route was allied to easy access to aryltetralin type 2-azalignan analogues. Synthesized 2-azalignans were tested for in vitro anticancer activity using a panel of human cancer cell lines. Both of two (1S)-diastereomers (9a and 9b) of 2-aza-4-deoxypodophyllotoxin showed significant activity against human cancer cell lines: A-549 (lung), HTC-8 (ileocecal), and MCF-7 (breast cancer).