Stereoselective synthesis of C5-C20 and C21-C34 subunits of the core structure of the aplyronines. Applications of enantioselective additions of chiral allenylindium reagents to chiral aldehydes.
The stereoselective synthesis of a C5-C20 and a C21-C34 subunit of the aplyronine family of polyketide marine macrolides has been achieved. These subunits contain all 15 stereocenters of the core structure. Six of the 15 stereocenters were introduced through enantioselective and diastereoselective additions of chiral allenylindium reagents to alpha-methyl-beta-oxygenated propionaldehydes. The products of these additions were further transformed by reactions involving the terminal alkynyl substituent produced in the addition reactions. Unlike previous applications of this methodology, the present synthesis employs Pd(0)-catalyzed transmetalations of chiral allenylpalladium intermediates to generate the chiral allenylindium reagents in situ.
Marshall
J A
JA
Department of Chemistry, University of Virginia, Charlottesville 22904, USA.
Johns
B A
BA
D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism; D000498:Allyl Compounds / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001048:Aplysia / Q000737:chemistry; D007204:Indium / Q000737:chemistry* / Q000378:metabolism; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000447:Aldehydes; D000498:Allyl Compounds; D000970:Antineoplastic Agents; D007783:Lactones; D018942:Macrolides; D007204:Indium; C104057:aplyronine A; D012694:Serine; D010165:Palladium