Studies toward the configurational assignment and total synthesis of reidispongiolide A
Reidispongiolide A (10) is a cytotoxic, marine macrolide that exerts inhibition of cell growth through actin-binding. Of particular interest is its efficacy against multi-drug resistant cancer cell lines. At the outset of the project the stereochemical configuration of reidispongiolide A was uncerta...
| Main Author: | |
|---|---|
| Published: |
University of Cambridge
2005
|
| Subjects: | |
| Online Access: | http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596190 |
| Summary: | Reidispongiolide A (10) is a cytotoxic, marine macrolide that exerts inhibition of cell growth through actin-binding. Of particular interest is its efficacy against multi-drug resistant cancer cell lines. At the outset of the project the stereochemical configuration of reidispongiolide A was uncertain and chemical degradation had been performed to enable further elucidation (Scheme A-1). Chapter 2 details the synthesis of possible diastereomers of the C<sub>23</sub>-C<sub>35</sub> and C<sub>5</sub>-C<sub>16</sub> degradation fragments 16 and 18. Identification of the correct diastereomer in each case allowed for a reduction in the number of possible diastereomers of reidispongiolide A from over a hundred to two. Chapter 3 uses the chemistry developed in the synthesis of the degradation fragments and applies this to the synthesis of the retrosynthetic fragments (Scheme A-2). Successful synthesis of the C<sub>14</sub>-C<sub>29</sub> ketone 126 (16 steps, 34%) and a C<sub>6</sub>-C<sub>13</sub> model aldehyde <i>ent</i>-168 allowed investigation of the pivotal C<sub>13</sub>-C<sub>14</sub> aldol coupling (Scheme A-3). A Mukaiyama aldol reaction proved to be the best method and proceeded under Felkin control to give a 3:1 <i>dr. </i> |
|---|