From Plant to Patient: Thapsigargin, a Tool for Understanding …
75
N
O
O
(CH 2 ) 11 COOH
O
O
O
O
OH
O
OH
O
O
O
(CH 2 ) 11
N
O
O
63
O
O
O
O
OH
O
OH
OH
O
O
(CH 2 ) 11
N
O
O
65
O
O
O
O
OH
OH
OH
OH
O
O
(CH 2 ) 11
N
O
O
64
O
O
O
HO
OH
O
OH
O
O
62
O
O
O
O
O
O
OH
O
O
61
O
O
O
O
O
O
O
OH
OH
OH
O
50
O
O
a
b
d
O
c
e
f
O
O
O
O
O
O
OH
OH
O
O
(CH 2 ) 11
N
O
O
66
O
O
Scheme 13 Selective acylation at O-2 and O-10. a dimethoxypropane and p-toluenesulfonic acid
in acetone; b KOH CH 3 OH; c DCC and DMAP in DCM; d HCl in CH 3 OH; e (CH 3 CH 2 CH 2 CO) 2 O
and pyridine in DCM; f isopropenyl acetate added p-toluenesulfonic acid
if isopropenyl esters were used. In these cases, better results were obtained if acid
anhydrides were used in the presence of p-toluenesulfonic acid (Scheme 13) [18].
6.4 Chemistry at O-7 and O-11
Thapsigargin (1) has never been isolated in a crystalline form, thus preventing X-ray
analysis of this compound. However, crystal structures at 2.1–2.2 Å resolution have
been determined for SERCA1a with bound thapsigargin [77], and conformational