title: The lyconadins: enantioselective total syntheses of (+)-lyconadin A and (-)-lyconadin B.
abstract: A full account of the enantioselective total syntheses of (+)-lyconadin A (1) and (-)-lyconadin B (2) is presented. Central to this venture was recognition and deployment of a key strategy-level intramolecular aldol/conjugate addition cascade that led, in a single operation, to two new carbon-carbon sigma-bonds, three new stereogenic centers, and two new rings, albeit with the incorrect stereogenicity at C(12) for the lyconadins. Correction of the C(12) stereogenicity was achieved via innovative use of a protonated intramolecular aminal. An aminoiodo olefin cyclization, in conjunction with alpha-pyridinone and 3,4-dihydropyridinone annulation protocols, permitted completion of the syntheses of (+)-lyconadin A (1) and (-)-lyconadin B (2), respectively.
authors.affiliation: Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Beshore
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry; D007454:Iodides / Q000737:chemistry; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D000470:Alkaloids; D006835:Hydrazones; D007454:Iodides; D011083:Polycyclic Compounds; C435307:lyconadin A; C514204:lyconadin B; C116609:3-hydroxybutanal
references.citation: Org Lett. 2007 Jul 5;9(14):2633-6
references.pmid: 17550259
references.citation: Bioorg Med Chem. 2006 Sep 1;14(17):5995-6000
references.pmid: 16750373
references.citation: Nat Prod Rep. 2004 Dec;21(6):752-72
references.pmid: 15565253
references.citation: Org Lett. 2006 Apr 27;8(9):1867-70
references.pmid: 16623571
references.citation: Nat Prod Rep. 2001 Feb;18(1):iii-v
references.pmid: 11245404
references.citation: Org Lett. 2002 Jul 25;4(15):2573-5
references.pmid: 12123379
references.citation: J Org Chem. 1996 Oct 4;61(20):6994-6996
references.pmid: 11667598
references.citation: J Org Chem. 1998 Aug 21;63(17):6016-6020
references.pmid: 11672206
references.citation: J Org Chem. 1996 Sep 20;61(19):6494-6495
references.pmid: 11667509
references.citation: Alkaloids Chem Biol. 2005;61:1-57
references.pmid: 16173399
references.citation: J Am Chem Soc. 2007 Apr 11;129(14):4148-9
references.pmid: 17367142
references.citation: Nat Prod Rep. 1991 Oct;8(5):455-63
references.pmid: 1766595
references.citation: Org Lett. 2008 Jan 17;10(2):285-8
references.pmid: 18154343
references.citation: J Org Chem. 2001 Aug 24;66(17):5901-4
references.pmid: 11511269
references.citation: J Am Chem Soc. 1977 Jan 19;99(2):556-61
references.pmid: 830692
references.citation: Bioorg Med Chem Lett. 2001 Oct 8;11(19):2627-30
references.pmid: 11551765
references.citation: J Am Chem Soc. 2008 Jun 11;130(23):7222-3
references.pmid: 18479095
references.citation: J Am Chem Soc. 1976 Jan 21;98(2):630-2
references.pmid: 1245689