From Plant to Patient: Thapsigargin, a Tool for Understanding …
71
O
O
O
O
O
O
O
O
O
OH
OH
O
O
O
O
O
O
OH
O
O
OH
OH
O
a
b
50
Scheme 7 Solvolysis of thapsigargin (1). a (CH 3 CH 2 ) 3 N, CH 3 OH; b NaOCH 2 CH 3 , CH 3 CH 2 OH
proceeds much slower, indicating the anchimeric assistance of this hydroxy group
for the cleavage of the ester [66].
For the large-scale production of debutanoyl thapsigargin (50), the solvolysis has
been performed with ethanolic sodium ethoxide at −15°C [67].
The secondary alcohol at C-8 can be oxidized to the corresponding ketone 51
(Scheme 8) [65]. Use of appropriate reductants can afford selective reduction to
the α-alcohol 50 with sodium borohydride [65] or to the epimeric β-alcohol 52 with
sodium triacetoxyborohydride [68]. Tritiation of thapsigargin (1) has been performed
using tritiated sodium borohydride as a reductant to give 1 tritiated at C-8 [65].
O
O
O
O
O
O
O
O
OH
OH
O
O
O
O
O
O
O
O
OH
OH
O
O
O
O
O
O
OH
O
O
OH
OH
O
OH
50
51
52
a
b
c
Scheme 8 a CrO 3 ; b NaBH 4 ; c Na(CH 3 COO) 3 BH