title: An Effective Bifunctional Aldehyde Linchpin for Type II Anion Relay Chemistry: Development and Application to the Synthesis of a C16-C29 Fragment of Rhizopodin.
abstract: The design, synthesis, and validation of a new bifunctional aldehyde linchpin for Type II anion relay chemistry have been achieved. For this linchpin, the initial nucleophilic addition proceeds under Felkin-Anh control to generate the syn-alkoxide, which undergoes a 1,4-Brook rearrangement to relay the negative charge, thus leading to the formation of a dithiane-stabilized carbanion. Subsequent trapping with an electrophile furnishes a tricomponent adduct with an embedded propionate subunit, a ubiquitous structural motif found in polyketides. The utility of this new linchpin is demonstrated with the construction of a potential C16-C29 fragment for the synthesis of rhizopodin, an actin-binding macrolide.
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Bruno
authors.initials: B
authors.lastname: Melillo
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Ming Z
authors.initials: MZ
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Roberto
authors.initials: R
authors.lastname: Forestieri
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000838:Anions / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D061065:Polyketides / Q000737:chemistry*; D011807:Quinolizines / Q000737:chemistry; D013457:Sulfur Compounds / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000838:Anions; D018942:Macrolides; D010080:Oxazoles; D061065:Polyketides; D011807:Quinolizines; D013457:Sulfur Compounds; C438055:dithiane; C081739:rhizopodin