270
J. C. Pardo-Novoa and C. M. Cerda-García-Rojas
2.4 Advanced Mosher’s Methods
The widely used Mosher’s method for the absolute configuration determination of
chiral compounds [43, 44] has benefited with the introduction of two improvements
that have been important in the structural elucidation of natural products and derivatives. These are (1) the implementation of this procedure for using directly in NMR
tubes [45], which has been crucial when the amount of material is limited, and (2)
the interpretation of the results in conjunction with molecular models, which have
been fundamental tools to evaluate the three-dimensional arrangement of the ester
derivatives, for a better understanding of the diamagnetic shielding effects.
Thus, the aerial parts of Mikania thapsoides afforded six sesquiterpene lactones
(100–105) with an unusual cis,cis-germacranolide skeleton and two melampolides
(106 and 107), all of them bearing a trans C-8 lactone ring closure. Their structural
elucidation was carried out using 1D and 2D NMR measurements and the absolute configuration of 100 was determined through the Mosher ester methodology
in combination with a molecular model calculated with molecular mechanics [46].
The (R)- and (S)-α-methoxy-α-trifluoromethylphenylacetate (MTPA) esters of 100
were prepared to determine the absolute configuration of the carbon atom bearing
the hydroxy group. The configuration at C-5 was deduced as (R) due to the high
shielding experienced by H-8 (δ 1.34 ppm) of the (R)-MTPA ester as compared to
the (S)-MTPA ester, which indicated that H-8 is strongly affected by the phenyl group
of the MTPA moiety. The H-7 shielding (δ 0.21 ppm) was smaller than that of H-8,
which was in agreement with the trans lactone ring closure [46].
O
OR
1
O
OR
2
OH
O
O
O
O
OSen
O
O
O
O
OSen
OAc
OR
OH
100 R
1 = Ac, R
2 = Sen
101 R
1 = Ac, R
2 = i-Val
102 R
1 = H, R
2 = Sen
103
104 R = Sen
105 R = i-Val
106 R = Sen
107 R = i-Val
1
2
3
4 5 6
7
8
9
10
11
12
13
14
15
Sen =
i-Val =
O
(
O
(
O
O
J. C. Pardo-Novoa and C. M. Cerda-García-Rojas
2.4 Advanced Mosher’s Methods
The widely used Mosher’s method for the absolute configuration determination of
chiral compounds [43, 44] has benefited with the introduction of two improvements
that have been important in the structural elucidation of natural products and derivatives. These are (1) the implementation of this procedure for using directly in NMR
tubes [45], which has been crucial when the amount of material is limited, and (2)
the interpretation of the results in conjunction with molecular models, which have
been fundamental tools to evaluate the three-dimensional arrangement of the ester
derivatives, for a better understanding of the diamagnetic shielding effects.
Thus, the aerial parts of Mikania thapsoides afforded six sesquiterpene lactones
(100–105) with an unusual cis,cis-germacranolide skeleton and two melampolides
(106 and 107), all of them bearing a trans C-8 lactone ring closure. Their structural
elucidation was carried out using 1D and 2D NMR measurements and the absolute configuration of 100 was determined through the Mosher ester methodology
in combination with a molecular model calculated with molecular mechanics [46].
The (R)- and (S)-α-methoxy-α-trifluoromethylphenylacetate (MTPA) esters of 100
were prepared to determine the absolute configuration of the carbon atom bearing
the hydroxy group. The configuration at C-5 was deduced as (R) due to the high
shielding experienced by H-8 (δ 1.34 ppm) of the (R)-MTPA ester as compared to
the (S)-MTPA ester, which indicated that H-8 is strongly affected by the phenyl group
of the MTPA moiety. The H-7 shielding (δ 0.21 ppm) was smaller than that of H-8,
which was in agreement with the trans lactone ring closure [46].
O
OR
1
O
OR
2
OH
O
O
O
O
OSen
O
O
O
O
OSen
OAc
OR
OH
100 R
1 = Ac, R
2 = Sen
101 R
1 = Ac, R
2 = i-Val
102 R
1 = H, R
2 = Sen
103
104 R = Sen
105 R = i-Val
106 R = Sen
107 R = i-Val
1
2
3
4 5 6
7
8
9
10
11
12
13
14
15
Sen =
i-Val =
O
(
O
(
O
O