16.4 16-Membered Macrocyclic Lactones
16.4.1 (–)-Spinosyn A
Laborious investigations of the best macrolactonization strategy were imperative
during synthetic studies on (–)-spinosyn A 214 (Scheme 60) [141]. Initial attempts
to effect the macrocyclization of 212 by using Mukaiyama [117] conditions provided the desired lactone 213 in only 33 % yield (Scheme 60, entry 1). Coste’s
peptide-coupling agent PyBrOP [130] 201 and the Yonemitsu variant [135] of the
Yamaguchi macrolactonization procedure provided 213 in equally low yield (37 %
and 38 %) (Scheme 60, entries 2 and 3). A significant improvement (48–54 %
isolated yield of 213) was achieved when the Mitsunobu [115, 116] conditions were
employed (Scheme 60, entries 4 and 5). Ultimately, the best results (70 % yield)
were obtained when the macrolactonization of 212 was performed by using Coste
et al. peptide-coupling agent benzotriazol-1-yloxytripyrrolidinophosphonium
hexafluorophosphate (PyBOP) [131] (202) at ambient temperature (Scheme 60,
entry 6).
Scheme 60 Various cyclization protocols used during synthetic studies on (–)-spinosyn A, 214
Synthesis of 12- to 16-Membered-Ring Lactones
415
16.4.1 (–)-Spinosyn A
Laborious investigations of the best macrolactonization strategy were imperative
during synthetic studies on (–)-spinosyn A 214 (Scheme 60) [141]. Initial attempts
to effect the macrocyclization of 212 by using Mukaiyama [117] conditions provided the desired lactone 213 in only 33 % yield (Scheme 60, entry 1). Coste’s
peptide-coupling agent PyBrOP [130] 201 and the Yonemitsu variant [135] of the
Yamaguchi macrolactonization procedure provided 213 in equally low yield (37 %
and 38 %) (Scheme 60, entries 2 and 3). A significant improvement (48–54 %
isolated yield of 213) was achieved when the Mitsunobu [115, 116] conditions were
employed (Scheme 60, entries 4 and 5). Ultimately, the best results (70 % yield)
were obtained when the macrolactonization of 212 was performed by using Coste
et al. peptide-coupling agent benzotriazol-1-yloxytripyrrolidinophosphonium
hexafluorophosphate (PyBOP) [131] (202) at ambient temperature (Scheme 60,
entry 6).
Scheme 60 Various cyclization protocols used during synthetic studies on (–)-spinosyn A, 214
Synthesis of 12- to 16-Membered-Ring Lactones
415