Liau, BrianMilgram, Benjamin CharlesShair, Matthew2012-09-262012Liau, Brian B., Benjamin C. Milgram, Matthew D. Shair. 2012. Total syntheses of HMP-Y1, hibarimicinone, and HMP-P1. Journal of the American Chemical Society 134(40): 16765–16772.0002-78631520-5126http://nrs.harvard.edu/urn-3:HUL.InstRepos:9639969Total 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 were 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. Lastly, 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.en-USJournal Article2012-09-2610.1021/ja307207q