13.4 14-Membered Macrocyclic Lactones
13.4.1 Leucascandrolide A
In the total synthesis of leucascandrolide A 159, Carreira et al. have shown that the
macrolactonization of the seco-acid of compound 157 (Scheme 45) under standard
conditions led mainly to oligomeric products, probably due to unfavorable hydrogen bond interactions. To disrupt these interactions, the Yamaguchi reaction was
carried out in DMF, giving the 14-membered methylated lactone 158 in 49 %
overall yield and none of the undesired 8-membered lactone [95].
13.5 15-Membered Macrocyclic Lactones
13.5.1 Amphidinolide J
During the total synthesis of amphidinolide J, 164, a 4/1 mixture of seco-acids 160
and 161 was subjected to macrolactonization under Yamaguchi conditions to afford
the 15-membered macrolactone 162 (34 %) and the undesired 14-membered
macrolactone 163 (24 %) which readily could be separated by flash chromatography on silica gel [96] (Scheme 46). Remarkably, 163 could be transformed to
amphidinolide J 164 by intramolecular transesterification.
Scheme 45 Representative example of a 14-membered macrocycle using a solvent modified
Yamaguchi protocol
404
M. Cordes and M. Kalesse
13.4.1 Leucascandrolide A
In the total synthesis of leucascandrolide A 159, Carreira et al. have shown that the
macrolactonization of the seco-acid of compound 157 (Scheme 45) under standard
conditions led mainly to oligomeric products, probably due to unfavorable hydrogen bond interactions. To disrupt these interactions, the Yamaguchi reaction was
carried out in DMF, giving the 14-membered methylated lactone 158 in 49 %
overall yield and none of the undesired 8-membered lactone [95].
13.5 15-Membered Macrocyclic Lactones
13.5.1 Amphidinolide J
During the total synthesis of amphidinolide J, 164, a 4/1 mixture of seco-acids 160
and 161 was subjected to macrolactonization under Yamaguchi conditions to afford
the 15-membered macrolactone 162 (34 %) and the undesired 14-membered
macrolactone 163 (24 %) which readily could be separated by flash chromatography on silica gel [96] (Scheme 46). Remarkably, 163 could be transformed to
amphidinolide J 164 by intramolecular transesterification.
Scheme 45 Representative example of a 14-membered macrocycle using a solvent modified
Yamaguchi protocol
404
M. Cordes and M. Kalesse