62
S. B. Christensen et al.
1 1
5 5 6 6 7 7
8 8
9 9
10 10
2 2
3 3
4 4
O
12 12
11 11
15 15
O
O
O
O
14 14
O
13 13
O
R
2
R
1
OH
OH
O
O
O
O
iVal =
2-MeBut =
Sen =
Ang =
6-MeOct =
O
R 3
O
6-MeHep =
O
O
O
O
O
O
O
O
O
O
O
16
1 R
1 = CH 3 (CH 2 ) 6 CO, R 2 = CH 3 (CH 2 ) 2 CO, R 3 = CH 3 CO (thapsigargin) [15, 17, 23, 24]
2 R
1 = CH 3 (CH 2 ) 4 CO, R 2 = CH 3 (CH 2 ) 2 CO, R 3 = CH 3 CO (thapsigargicin) [15, 17, 23, 24]
3 R
1 = iVal,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsitranstagin) [27–30]
4 R
1 = Ang,
R 2 = Sen,
R 3 = CH 3 CO (thapsivillosin A) [28, 29]
5 R 1 = Ang,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin B) [27–29]
6 R
1 = CH 3 (CH 2 ) 6 CO, R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin C) [28, 30]
7 R
1 = 6-MeOct,
R 2 = Sen,
R 3 = CH 3 CO (thapsivillosin D) [28, 30]
8 R 1 = 6-MeOct,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin E) [28]
9 R
1 = 6-MeHep,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin G) [28]
10 R
1 = Ang or Sen,
R 2 = Sen or Ang,
R 3 = C H 3 CO (thapsivillosin H) [28]
11 R
1 = Ang,
R 2 = C H 3 (CH2) 2 CO, R 3 = CH 3 CO (thapsivillosin I) [27, 28]
12 R
1 = iVal,
R 2 = C H 3 (CH2) 2 CO, R 3 = CH 3 CO (thapsivillosin J) [27, 28]
13 R
1 = Sen,
R 2 = CH 3 (CH2) 2 CO, R 3 = CH 3 CO (thapsivillosin K) [27, 28]
14 R
1 = CH 3 CO,
R 2 = 2-MeBut,
R 3 = CH 3 CO (acetyltrilobolide) [25]
15 R
1 = H,
R 2 = 2-MeBut,
R 3 = H (2-hydroxy-10- O-deacetyl trilobilide) [25]
2
6
6
Fig. 2 Hexaoxygenated guaianolides containing the thapsigargin skeleton isolated from plants
belonging to the genera Thapsia and Laser. The epoxide 16 is a synthon prepared for structure
elucidation (Section 6.4) [15, 17, 23–25, 27–30]
reports of the plants being poisonous [7]. The root bark and the resin of Thapsia have
been used in Arabic and European medicine, with Hippocrates first describing the
skin-irritant effects of Thapsia around 400 BC. Since then, the roots, in particular,
and the resin have been used in traditional medicine. Theophrastus (circa 327–287
BCE) described the properties of the roots of Thapsia as being able to “purge both
upwards and downwards” if ingested, and that, while domestic cattle in Greece did
S. B. Christensen et al.
1 1
5 5 6 6 7 7
8 8
9 9
10 10
2 2
3 3
4 4
O
12 12
11 11
15 15
O
O
O
O
14 14
O
13 13
O
R
2
R
1
OH
OH
O
O
O
O
iVal =
2-MeBut =
Sen =
Ang =
6-MeOct =
O
R 3
O
6-MeHep =
O
O
O
O
O
O
O
O
O
O
O
16
1 R
1 = CH 3 (CH 2 ) 6 CO, R 2 = CH 3 (CH 2 ) 2 CO, R 3 = CH 3 CO (thapsigargin) [15, 17, 23, 24]
2 R
1 = CH 3 (CH 2 ) 4 CO, R 2 = CH 3 (CH 2 ) 2 CO, R 3 = CH 3 CO (thapsigargicin) [15, 17, 23, 24]
3 R
1 = iVal,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsitranstagin) [27–30]
4 R
1 = Ang,
R 2 = Sen,
R 3 = CH 3 CO (thapsivillosin A) [28, 29]
5 R 1 = Ang,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin B) [27–29]
6 R
1 = CH 3 (CH 2 ) 6 CO, R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin C) [28, 30]
7 R
1 = 6-MeOct,
R 2 = Sen,
R 3 = CH 3 CO (thapsivillosin D) [28, 30]
8 R 1 = 6-MeOct,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin E) [28]
9 R
1 = 6-MeHep,
R 2 = 2-MeBut,
R 3 = CH 3 CO (thapsivillosin G) [28]
10 R
1 = Ang or Sen,
R 2 = Sen or Ang,
R 3 = C H 3 CO (thapsivillosin H) [28]
11 R
1 = Ang,
R 2 = C H 3 (CH2) 2 CO, R 3 = CH 3 CO (thapsivillosin I) [27, 28]
12 R
1 = iVal,
R 2 = C H 3 (CH2) 2 CO, R 3 = CH 3 CO (thapsivillosin J) [27, 28]
13 R
1 = Sen,
R 2 = CH 3 (CH2) 2 CO, R 3 = CH 3 CO (thapsivillosin K) [27, 28]
14 R
1 = CH 3 CO,
R 2 = 2-MeBut,
R 3 = CH 3 CO (acetyltrilobolide) [25]
15 R
1 = H,
R 2 = 2-MeBut,
R 3 = H (2-hydroxy-10- O-deacetyl trilobilide) [25]
2
6
6
Fig. 2 Hexaoxygenated guaianolides containing the thapsigargin skeleton isolated from plants
belonging to the genera Thapsia and Laser. The epoxide 16 is a synthon prepared for structure
elucidation (Section 6.4) [15, 17, 23–25, 27–30]
reports of the plants being poisonous [7]. The root bark and the resin of Thapsia have
been used in Arabic and European medicine, with Hippocrates first describing the
skin-irritant effects of Thapsia around 400 BC. Since then, the roots, in particular,
and the resin have been used in traditional medicine. Theophrastus (circa 327–287
BCE) described the properties of the roots of Thapsia as being able to “purge both
upwards and downwards” if ingested, and that, while domestic cattle in Greece did