title: Asymmetric syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine.
abstract: The highly diastereoselective conjugate additions of the novel lithium amide reagents lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide and lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to α,β-unsaturated esters were used as the key steps in syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine. The asymmetric synthesis of (-)-(S,S)-homaline was achieved in 8 steps and 18% overall yield, and the asymmetric synthesis of (-)-(R,R)-hopromine was achieved in 9 steps and 23% overall yield, from commercially available starting materials in each case. These syntheses therefore represent by far the most efficient total asymmetric syntheses of these alkaloids reported to date. A sample of the (4'R,4''S)-epimer of hopromine was also produced using this approach, which provided the first unambiguous confirmation of its absolute configuration and therefore that of natural (-)-(R,R)-hopromine.
authors: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK. steve.davies@chem.ox.ac.uk
authors: Stephen G
authors: SG
authors: Davies
authors: James A
authors: JA
authors: Lee
authors: Paul M
authors: PM
authors: Roberts
authors: Jeffrey P
authors: JP
authors: Stonehouse
authors: James E
authors: JE
authors: Thomson
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D000577:Amides / Q000737:chemistry*; D004952:Esters; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000577:Amides; D004952:Esters; C576843:homaline; C576844:hopromine; D008094:Lithium