2.4 Final Synthetic Route to Hederagonic Acid
37
acid, affording the target product 1 in 95 % yield. Hederagonic acid (1) is
thus synthesised in 4 steps and 20 % overall yield.
HO
H
H
OH
O
H
N
H
H
O
H
HO
Br
O
N
O
O
O
O
O
H
H
OH
O
H
HO
H
H
O
H
Br
O
O
HO
H
H
O
H
Br
O
Pyridine (15.2 equiv)
DCM, 20 °C
(99 %)
(4)
AcOH, 40 °C
(95 %)
Zn (30 equiv)
(2a)
(b)
Ac 2 O (26 equiv)
Pd(OAc) 2 (15 mol-%),
PhI(OAc) 2 (1.6 equiv)
AcOH, 40 °C
(48 %)
(3a)
(b)
K 2 CO 3 (1 equiv),
CuSO 4 (5 equiv),
H 2 O/THF
MeOH, 60 °C
(55 %)
NBS (1.05 equiv)
TCCA (0.8 equiv),
then i-PrOH
(0.8 equiv)
NH 2 OH · HCl
(3.2 equiv)
(1a)
(b)
(c)
5
6 b
7b
(dr 75:25)
8b
1
Scheme 2.25: The herein reported semisynthesis of hederagonic acid (1). Reagents and conditions: (1) DCM, pyridine, 20 °C. (a) NBS,
60 min. (b) TCCA, 90 min, then i-PrOH, 30 min. (c) Hydroxylamine hydrochloride, 21 h. (2) AcOH, 40 °C. (a) Ac2O, 2 h. (b)
PhI(OAc)2, Pd(OAc)2, 16 h. (3) MeOH, 60 °C. (a) K2CO3, 1 h.
(b) THF, CuSO4 · 5 H2O in H2O, 16 h. (4) Zn, AcOH, 40 °C, 2 h.