New Techniques of Structure Elucidation for Sesquiterpenes
303
mass spectrometry, and X-ray diffraction analysis. The absolute configurations of
epoxide 293 and that of compound 296, which involved a molecular rearrangement of
the epoxide group with a transannular 1,5-hydride shift, were verified by calculation
of the Flack (x) and Hooft (y) parameters that gave x = −0.03(19) and y = −
0.00(6) for 293 and x = 0.10(3) and y = 0.07(14) for 296. Inversion of the absolute
configuration of the X-ray structures increased these parameters to x = 1.03(19) and
y = 1.00(5) for 293 and x = 0.90(3) and y = 0.93(14) for 296. Confirmation of
the absolute configuration of the parvifoline derivatives was an important task to be
achieved considering their biological interactions with tubulin, which were studied
by using in vitro experiments and by docking analysis. Compounds 288, 292, and
295 inhibited the polymerization of the α,β-tubulin heterodimer by 24%, 49%, and
90% as compared to colchicine. Competitive inhibition of 288, 292, and 295 with
colchicine were also investigated to support their binding at the colchicine secondary
site in α-tubulin, while evaluations of their cytotoxicity on cancer cell lines showed
that 295 was active against the HeLa cervix carcinoma and HCT 116 colon carcinoma
lines with IC 50 3.3 ± 0.2 and 5.0 ± 0.5 μM, respectively [120].
RO
RO
RO
RO
RO
O
O
O
RO
O
288 R = H (parvifoline)
289 R = Bz
290 R = H
291 R = Bz
292 R = H
293 R = Bz
294 R = H
295 R = Bz
296 R = H
297 R = Bz
298 R = H
299 R = Bz
5 Conclusions
Although research on many aspects of sesquiterpenes has been developed extensively
during this present century, the chapter focuses on summarizing reported laboratory
investigations that have incorporated new successful techniques for the structure
determination of this representative group of organic natural products. The information contained in this contribution has allowed a presentation of the panorama of
several new tools that are accessible to natural product researchers currently. It is
relevant to point out that the structure elucidation strategies applied in the articles
that have been cited can be extrapolated to other groups of naturally occurring and
synthetic compounds.
The importance of having precise three-dimensional structures through validated
molecular models of sesquiterpenes is of high relevance, because they are very useful
303
mass spectrometry, and X-ray diffraction analysis. The absolute configurations of
epoxide 293 and that of compound 296, which involved a molecular rearrangement of
the epoxide group with a transannular 1,5-hydride shift, were verified by calculation
of the Flack (x) and Hooft (y) parameters that gave x = −0.03(19) and y = −
0.00(6) for 293 and x = 0.10(3) and y = 0.07(14) for 296. Inversion of the absolute
configuration of the X-ray structures increased these parameters to x = 1.03(19) and
y = 1.00(5) for 293 and x = 0.90(3) and y = 0.93(14) for 296. Confirmation of
the absolute configuration of the parvifoline derivatives was an important task to be
achieved considering their biological interactions with tubulin, which were studied
by using in vitro experiments and by docking analysis. Compounds 288, 292, and
295 inhibited the polymerization of the α,β-tubulin heterodimer by 24%, 49%, and
90% as compared to colchicine. Competitive inhibition of 288, 292, and 295 with
colchicine were also investigated to support their binding at the colchicine secondary
site in α-tubulin, while evaluations of their cytotoxicity on cancer cell lines showed
that 295 was active against the HeLa cervix carcinoma and HCT 116 colon carcinoma
lines with IC 50 3.3 ± 0.2 and 5.0 ± 0.5 μM, respectively [120].
RO
RO
RO
RO
RO
O
O
O
RO
O
288 R = H (parvifoline)
289 R = Bz
290 R = H
291 R = Bz
292 R = H
293 R = Bz
294 R = H
295 R = Bz
296 R = H
297 R = Bz
298 R = H
299 R = Bz
5 Conclusions
Although research on many aspects of sesquiterpenes has been developed extensively
during this present century, the chapter focuses on summarizing reported laboratory
investigations that have incorporated new successful techniques for the structure
determination of this representative group of organic natural products. The information contained in this contribution has allowed a presentation of the panorama of
several new tools that are accessible to natural product researchers currently. It is
relevant to point out that the structure elucidation strategies applied in the articles
that have been cited can be extrapolated to other groups of naturally occurring and
synthetic compounds.
The importance of having precise three-dimensional structures through validated
molecular models of sesquiterpenes is of high relevance, because they are very useful