Total Synthesis of Sarcodictyins A and B
1998-08-13T00:00:00Z (GMT) by
The total synthesis of cytotoxic marine natural products possessing tubulin polymerization and microtubule stabilization properties, sarcodictyins A (<b>7</b>) and B (<b>8</b>), is described. Two related approaches to these target molecules have been developed, both utilizing (+)-carvone (<b>9</b>) as starting material. The first approach involves a stereoselective construction of acetylenic aldehyde <b>27</b> (Scheme ) while the second approach proceeds through a more direct but less selective sequence to the similar intermediate <b>36</b> (Scheme ). Both strategies involve ring closures of the acetylenic aldehyde precursors to 10-membered rings under basic conditions followed by elaboration and selective reduction of the acetylenic linkage to a <i>cis</i> double bond. This promotes bridging to form the required tricyclic skeleton of the sarcodictyins (<b>27</b> → <b>37</b> → <b>38</b> → <b>39</b> → <b>4</b>, Scheme and <b>37</b> → <b>44</b> → <b>45</b> → <b>46</b> → <b>47</b> → <b>42</b>, Scheme ) and (<b>36</b> → <b>48</b> → <b>45</b>, Scheme ). Installation of the (<i>E</i>)-<i>N</i>(6‘)-methylurocanic acid residue was achieved by esterification with mixed anhydride <b>52</b>, while the C-3 ester moieties were installed by standard deprotection, oxidation, and esterification procedures.