62338-59-4Relevant articles and documents
Total synthesis of (-)-ebelactone A and B
Paterson,Hulme
, p. 3288 - 3300 (2007/10/02)
The β-lactone enzyme inhibitors (-)-ebelactone A (1) and (-)-ebelactone B (2) have been prepared in 12 steps from diethyl ketone (4 and 3% overall yield, respectively). The synthetic strategy adopted for the ebelactones demonstrates the use of reagent- and substrate-derived stereocontrol and requires the minimal use of protecting groups. The stereocenters at C2, C3, C8, C10, and C11 were constructed using boron aldol methodology. An asymmetric syn aldol addition of diethyl ketone to 2-ethylacrolein gave adduct 8 in 86% ee, followed by a diastereoselective syn aldol reaction to give 11. Subsequently, an Ireland-Claisen rearrangement was used to relay 1,2-syn into 1,5-syn relative stereochemistry, as in 12 → 14. In the anti aldol construction of the C2-C3 bond, the use of either a propionate or butyrate thioester enolate allowed for a divergent approach from aldehyde 17 to both (-)-ebelactone A and B. Several novel analogues of ebelactone A and B were also prepared with inverted stereochemistry at C2, C3, or C12.
