10.1021/ja981062g.s001
K. C. Nicolaou
K. C.
Nicolaou
J. Y. Xu
J. Y.
Xu
S. Kim
S.
Kim
J. Pfefferkorn
J.
Pfefferkorn
T. Ohshima
T.
Ohshima
D. Vourloumis
D.
Vourloumis
S. Hosokawa
S.
Hosokawa
Total Synthesis of Sarcodictyins A and B
American Chemical Society
1998
sarcodictyin
anhydride 52
Total Synthesis
tricyclic skeleton
acetylenic aldehyde 27
acetylenic linkage
ring closures
esterification procedures
cytotoxic marine
tubulin polymerization
target molecules
Scheme
microtubule stabilization properties
acetylenic aldehyde precursors
stereoselective construction
approach proceeds
1998-08-13 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Total_Synthesis_of_Sarcodictyins_A_and_B/3670185
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.