Diversification of structurally significant cycloartane-type triterpenes: exploiting beddomeilactone

The cycloartane-type triterpenes are a structurally important class of natural products with diverse biological activity. Here, we present synthetic strategies and chemical modifications for obtaining a number of recently reported cycloartane-type triterpenes, along with various close-to-natural novel derivatives. The naturally abundant beddomeilactone (<b>1</b>) serves as the key resource for most transformations. Notably, the linear sequences we put forward for synthesising three natural products from <b>1</b>, include the selective reduction of <b>1</b> to generate the <b>2</b> with desired stereochemistry, the lactonization of <b>2</b> gives <b>3</b> qualitatively, and a selective olefin reduction of <b>3</b> gives <b>11</b>. Further selective olefin reduction of <b>1</b> and <b>2</b> was carried out in order to produce dihydro-analogues (<b>15</b> and <b>17</b>). Acid-catalyzed esterification of <b>1</b> led to retro-aldol, forming novel analogue <b>18</b>; also synthesised the expected ester derivative <b>5</b>. Subsequent transformations, such as epoxidation, lactone ring opening, and amidation, produced diverse synthetic analogues (<b>19–21</b>). We also efficiently converted compound <b>4</b> into 2,4-<i>epi</i>-­binectarilactone (<b>22</b>), a structural analogue of <b>3</b>.