Stereoselective synthesis and biological evaluation of anisomycin and 2-substituted analogues

The naturally occurring pyrrolidine anisomycin I, its deacetyl derivative 9k, and some previously unknown analogues were prepared from 2-O-benzyl-3,4-O-isopropylidene-L-threose 2, via the N-benzylimine 3, using highly threo-selective additions of organolithium and Grignard compounds and subsequent cyclization as key steps. Anisomycin 1 was obtained in 8 steps/44% total yield from L-threose 2 (12 steps/23% from diethyl L-tartrate). The overall yields for deacetylanisomycin 9k were 54% (5 steps from L-threose 2) and 28% (9 steps from diethyl L-tartrate), respectively. The compounds 1, 8i, 8k, 9k, 18, 20, and 23 showed good to high cytotoxic activity towards three tumour and non-tumour cell lines.