title: Synthesis of two subunits of the macrolide domain of the immunosuppressive agent sanglifehrin a and assembly of a macrolactone precursor. application of masamune anti-aldol condensation.
abstract: Asymmetric anti-aldol coupling of a norephedrine-derived ester with an α-chiral aldehyde was used to synthesize a carboxylic acid representing the C13-C19 segment of the macrocyclic domain present in the immunosuppressive agent sanglifehrin A. Felkin addition set configuration at the C14-C17 stereotetrad in this unit in which hydroxyl functions at C15 and C17 were masked as an internal ketal. The carboxyl group of this segment was coupled to the N-terminus of the tripeptide portion (C1-N12) of sanglifehrin A macrolactone to assemble the C1-C19 domain. Synthesis of the C20-C25 subunit of sanglifehrin A containing a (23S) alcohol was completed via asymmetric allylation of (E)-3-iodo-2-methylprop-2-enal followed by oxidative cleavage of the terminal vinyl appendage and a Takai olefination with pinacol dichloromethylboronate. Esterification of this alcohol with a C1-C19 carboxylic acid furnished an open C1-C25 macrolactone precursor, but this substance failed to undergo macrocyclization via intramolecular Suzuki-Miyaura coupling.
authors.affiliation: Department of Chemistry, Oregon State University , Corvallis, Oregon 97331, United States.
authors.forename: Khomson
authors.initials: K
authors.lastname: Suttisintong
authors.forename: James D
authors.initials: JD
authors.lastname: White
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000438:Alcohols; D007166:Immunosuppressive Agents; D007783:Lactones; D018942:Macrolides; D013141:Spiro Compounds; C121329:sanglifehrin A