title: Total syntheses of HMP-Y1, hibarimicinone, and HMP-P1.
abstract: Total syntheses of HMP-Y1, atrop-HMP-Y1, hibarimicinone, atrop-hibarimicinone, and HMP-P1 are described using a two-directional synthesis strategy. A novel benzyl fluoride Michael-Claisen reaction sequence was developed to construct the complete carbon skeleton of HMP-Y1 and atrop-HMP-Y1 via a symmetrical, two-directional, double annulation. Through efforts to convert HMP-Y1 derivatives to hibarimicinone and HMP-P1, a biomimetic mono-oxidation to desymmetrize protected HMP-Y1 was realized. A two-directional unsymmetrical double annulation and biomimetic etherification was developed to construct the polycyclic and highly oxidized skeleton of hibarimicinone, atrop-hibarimicinone, and HMP-P1. The use of a racemic biaryl precursor allowed for the synthesis of both hibarimicinone atropisomers and provides the first confirmation of the structure of atrop-hibarimicinone. Additionally, this work documents the first reported full characterization of atrop-hibarimicinone, HMP-Y1, atrop-HMP-Y1, and HMP-P1. Last, a pH-dependent rotational barrier about the C2-C2' bond of hibarimicinone was discovered, which provides valuable information necessary to achieve syntheses of the glycosylated congeners of hibarimicinone.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Liau
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Milgram
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Shair
mesh_terms: D039903:Actinobacteria / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D032701:Biomimetics; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D009279:Naphthacenes / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D004987:Ethers; D006027:Glycosides; D009279:Naphthacenes; C456033:hibarimicinone