title: Absolute configuration assignment by asymmetric syntheses of the homalium alkaloids (-)-(R,R,R)-hoprominol and (-)-(4'S,4″R,2‴R)-hopromalinol.
abstract: The conjugate addition of lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide to α,β-unsaturated esters was used as the key step in the syntheses of all possible diastereoisomers of the homalium alkaloids hoprominol and hopromalinol. Comparison of the specific rotation data for these synthetic samples with those of samples isolated from the natural source enabled the absolute configurations within these alkaloids to be confidently assigned for the first time as (-)-(R,R,R)-hoprominol and (-)-(4'S,4″R,2‴R)-hopromalinol. The asymmetric syntheses of (-)-(R,R,R)-hoprominol (in 10 steps and 4.0% overall yield) and (-)-(4'S,4″R,2‴R)-hopromalinol (in 10 steps and 9.3% overall yield), from commercially available starting materials in each case, therefore represent the first total asymmetric syntheses of these alkaloids to be reported.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom. steve.davies@chem.ox.ac.uk
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Stonehouse
authors.forename: James E
authors.initials: JE
authors.lastname: Thomson
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018020:Lithium Compounds / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000577:Amides; D006571:Heterocyclic Compounds; D018020:Lithium Compounds; C578828:hopromalinol; C578827:hoprominol