Asymmetric total synthesis of sperabillins B and D via lithium amide conjugate addition.
Davies SG., Haggitt JR., Ichihara O., Kelly RJ., Leech MA., Price Mortimer AJ., Roberts PM., Smith AD.
Diastereoselective conjugate addition of homochiral lithium (R)-N-allyl-N-alpha-methylbenzylamide to methyl (2E,5E)-hepatadienoate, followed by protecting group manipulation and subsequent iodocyclocarbamation allows a concise route to the core fragment, methyl (3R,5R,6R)-3,6-diamino-5-hydroxyheptanoate, of sperabillins B and D. Differentiation between the C-3 and C-6 primary amino groups of this core amino acid was readily achieved by treatment with acetone, giving the 5,6-isopropylidene and C-3-imine protected diamine, with subsequent regioselective acylation of the C-6-nitrogen facilitating the total synthesis of sperabillin D in 10.8% overall yield, and the first asymmetric synthesis of sperabillin B in 5.8% overall yield.