The naturally occurring pyrrolidine anisomycin I, its deacetyl derivative 9
k, 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-s
elective additions of organolithium and Grignard compounds and subsequent c
yclization as key steps. Anisomycin 1 was obtained in 8 steps/44% total yie
ld from L-threose 2 (12 steps/23% from diethyl L-tartrate). The overall yie
lds 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 tumou
r and non-tumour cell lines.