The synthesis of bryostatins and related congeners contains some of the most
complex examples of Prins cyclizations in natural products synthesis. Simultaneous
reports by both Wender and coworkers and Keck et al. illustrate the power
and tolerance of Prins cyclization on complex bryostatin analogs (Scheme 42)
O
CO 2 Me
A
Br
BnO
HO
CO 2 Me
BnO
O
InBr 3 , TMSBr
–78 °C
65%
O
O
O
OH
O
O
CO 2 H
OBn
A
B
C
Cl
O
O
O
OH
OTBS
O
O
CO 2 H
OBn
A
C
In(OTf) 3 , TMSCl
CH 2 Cl 2 , –78 to –40 °C
147
148
149
150
151
152
+
42%
(eq 1)
(eq 2)
H
H
Scheme 40 Indium(III)-promoted Prins cyclization in the progress toward (+)-SCH 351488 [83]
O
O
A
BnO
SEM
O
O
BnO
1)
TiBr 4 , 2,6-DTBMP
CH 2 Cl 2 , –78 °C
2) Bu 3 SnH, AIBN
3) SEMCl, DIPEA
55%
ONpt
ONpt
O
B
OBn
HO
OAc
O
OBn
TIPSO
1) SnBr 4 , –78 °C
2) Bu 3 SnH, NaBH 4
EtOH, then 3 M HCl
55%
153
154
155
156
157
(eq 1)
(eq 2)
H
Scheme 41 MAP and Prins approaches to key intermediates for (+)-SCH 351488 [84]
68
M.A. Perry et al.