Elucidation of the stereostructure of the annonaceous acetogenin (+)-montecristin through total synthesis
Abstract
Total syntheses of ent-5-epi-montecristin
(1a) and of (−)-montecristin (1b) were accomplished.
The stereocenters of compounds 1a and 1b were established
by asymmetric dihydroxylations of the trans-configurated β,γ-unsaturated
esters 6 ( →
4, up to 80% ee; Scheme 3; improved
procedure with up to 94% ee: Scheme 7) and 56 ( →
55, 97% ee: Scheme 9) while the stereogenic CC bonds
stem from the carbocuprations 48
→
49 and 50
→
51 (Scheme 9). Treating hydroxylactones 27 (Scheme 7),
3a (Scheme 12) and 3b (Scheme 13) with PPh3 and DEAD,
we found a racemization-free dehydration giving butenolide 26 and
epimerization-free dehydrations giving butenolides 2a and 2b
. Relating the [α]D values of synthetic
1a and 1b to the [α]D value
of natural (+)-montecristin, the absolute configuration of its side-chain
stereocenters was determined to be R.