5.3 15-Membered Macrocyclic Lactones
5.3.1 (–)-Amphidinolide P
In the total synthesis of (–)-amphidinolide P 95, an intramolecular transesterification was carried out by heating hydroxy β-keto ester 93 in refluxing toluene,
which gave pure macrocycle 94 in 72 % yield certainly via a ketene intermediate
[65] (Scheme 23).
5.4 16-Membered Macrocyclic Lactones
5.4.1 (–)-A26771B
In a more recent application of dioxolenone thermolysis, Blechert et al. reported a
key acylketene lactonization which enables the synthesis of the 16-membered
macrolide antibiotic (–)-A26771B 98. Refluxing a dilute solution (125 μM) of 96
in n-heptane initiated the formation of an acylketene which was trapped by the
pendant secondary alcohol to give macrolactone 97 [66] (Scheme 24). This
advanced intermediate could then be elaborated into (–)-A26771B 98 over the
course of six steps in high yield.
Scheme 22 β-Keto ester thermolysis and following macrolactonization in the total synthesis of
norzoanthamine, 92
Synthesis of 12- to 16-Membered-Ring Lactones
389
5.3.1 (–)-Amphidinolide P
In the total synthesis of (–)-amphidinolide P 95, an intramolecular transesterification was carried out by heating hydroxy β-keto ester 93 in refluxing toluene,
which gave pure macrocycle 94 in 72 % yield certainly via a ketene intermediate
[65] (Scheme 23).
5.4 16-Membered Macrocyclic Lactones
5.4.1 (–)-A26771B
In a more recent application of dioxolenone thermolysis, Blechert et al. reported a
key acylketene lactonization which enables the synthesis of the 16-membered
macrolide antibiotic (–)-A26771B 98. Refluxing a dilute solution (125 μM) of 96
in n-heptane initiated the formation of an acylketene which was trapped by the
pendant secondary alcohol to give macrolactone 97 [66] (Scheme 24). This
advanced intermediate could then be elaborated into (–)-A26771B 98 over the
course of six steps in high yield.
Scheme 22 β-Keto ester thermolysis and following macrolactonization in the total synthesis of
norzoanthamine, 92
Synthesis of 12- to 16-Membered-Ring Lactones
389