Study Toward the Total Synthesis of Pyrenophorin

<div class="WordSection1"><p><em>Macrodiolides are macrocyclic compounds containing two ester groups in a cyclic chain. Of this class of compounds, Pyrenophorin (<strong>1</strong>) shows antifungal activity, and is produced from the pathogenic fungus Pyrenophora avenae. As this substance, derived from nature, is isolated in small quantities, an asymmetric synthesis using a simple and efficient methodology would be of great interest. The proposed synthetic route starts with the protection of propargyl alcohol <strong>3</strong> using DHP and feldspar as catalyst. Compound <strong>5</strong> obtained in this reaction was then subjected to acid-base reaction between the acetylenic proton and 1 eq. n-BuLi, leading to formation of the acetylide <strong>5A</strong>. The 1,2- addition reaction between <strong>5A</strong> and </em><em>g</em><em>-valerolactone (<strong>6</strong>) leads to the formation of alkinone <strong>7</strong> in 67% yield. Subsequently, compound <strong>7</strong> was subjected to a ketalization reaction using the same feldspar catalyst. Ketal <strong>8</strong> was formed under concomitant removal of the THP group. The product of this reaction (<strong>8</strong>) was then submitted to a reduction reaction of the triple bond to form olefin <strong>9</strong> with E configuration. Currently, the conditions for obtaining <strong>10</strong> by oxidation using Jones reagent, are being optimized.</em><em> </em><em>Compound <strong>10</strong>, obtained as</em><em> described, is being subjected to a macrolactonization reaction. Various conditions including the use of enzymes are being studied. In addition, a study involving the enantioselective synthesis of (R,R)-(-)-pyrenophorin, using enzymatic kinetic resolution of the racemic mixture of compound <strong>8</strong>, is in progress in the group</em></p></div>

Abstract licence: CC BY-NC-ND

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.