The Role of Total Synthesis in Structure …
23
modiolide A synthesis [84]. Compound 84 was identical to that intermediate in every
regard, including the sign and value of the specific rotation.
A close inspection of the analytical data reported for natural [68] and synthetic
[84] modiolide A (61) with those reported for fusanolide B (60) by Shimada et al.
in 2002 [64] revealed only very small differences that cannot be plausibly explained
by the different configuration at C-4. The only notable differences were observed
for the value of the specific rotations, but all three were dextrorotatory (see Chart 1
and Scheme 16). As first pointed out by Quang et al. in 2018 [82], who isolated
modiolides A (61) and B (62) together with the four new modiolides D–G from the
marine fungus Paraconiothyrium sp. VK-13, it has been proved that the originally
assigned structure of fusanolide B (60) is incorrect and that actually modiolide A
(61) was isolated from Fusarium sp. by Shimada et al. [64]. Interestingly, two of the
four new modiolides isolated and characterized by Quang et al., modiolide F (65)
and modiolide G (66), have an all-cis relative configuration (deduced from H,Hcoupling constants and NOESY spectra) as originally proposed for fusanolide B
(60). A comparison of the analytical data obtained for the new metabolite modiolide
G (66) [82] with those reported for “fusanolide B” [64] and modiolide A (61) [68,
84] shows substantial differences that underline the necessity to revise the structure
of “fusanolide B”. Remarkably, the new modiolides F (65) and G (66) have been
assigned the (S)-configuration at C-9, in contrast to the other modiolides (or most
ten-membered lactone natural products in general). The absolute configuration at C4 was determined as (R) for modiolide G (66), based on Mosher’s method, and from
there the absolute configurations at C-7 and C-9 were deduced to be the opposite of
those in modiolide A (61) [82].
3.2 Stagonolides and Curvulide A
Stagonolide A (85), originally named stagonolide, was first isolated and characterized
in 2007 by Yuzikhin et al. from culture filtrates of Stagonospora cirsii [87]. This
fungus is a pathogen that affects Cirsium arvense, the field or Canada thistle, a
perennial weed that is difficult to control in agriculture by mechanical means or with
common herbicides [88]. Stagonolide A (85) was shown to have strong phytotoxic
activity against C. arvense by inhibiting root growth and photosynthesis, and was
therefore proposed as a lead structure for novel herbicides derived from fungal plant
pathogens [87, 88] (Chart 2).
Shortly after this seminal investigation, several other ten-membered lactones
were isolated from Stagonospora cirsii, structurally characterized and tested for
their phytotoxic activity against C. arvense: stagonolides B–F (83, 86–89) [89] and
stagonolides G–I (90–92) [78] were discovered in 2008 by Evidente et al.; stagonolides J (93) and K (94), the most recent members of the stagonolide family, were
isolated in 2019 by Dalinova et al. [90]. The ten-membered lactone curvulide A
(95) has not been isolated from cultures of Stagonospora cirsii, but from the marine
23
modiolide A synthesis [84]. Compound 84 was identical to that intermediate in every
regard, including the sign and value of the specific rotation.
A close inspection of the analytical data reported for natural [68] and synthetic
[84] modiolide A (61) with those reported for fusanolide B (60) by Shimada et al.
in 2002 [64] revealed only very small differences that cannot be plausibly explained
by the different configuration at C-4. The only notable differences were observed
for the value of the specific rotations, but all three were dextrorotatory (see Chart 1
and Scheme 16). As first pointed out by Quang et al. in 2018 [82], who isolated
modiolides A (61) and B (62) together with the four new modiolides D–G from the
marine fungus Paraconiothyrium sp. VK-13, it has been proved that the originally
assigned structure of fusanolide B (60) is incorrect and that actually modiolide A
(61) was isolated from Fusarium sp. by Shimada et al. [64]. Interestingly, two of the
four new modiolides isolated and characterized by Quang et al., modiolide F (65)
and modiolide G (66), have an all-cis relative configuration (deduced from H,Hcoupling constants and NOESY spectra) as originally proposed for fusanolide B
(60). A comparison of the analytical data obtained for the new metabolite modiolide
G (66) [82] with those reported for “fusanolide B” [64] and modiolide A (61) [68,
84] shows substantial differences that underline the necessity to revise the structure
of “fusanolide B”. Remarkably, the new modiolides F (65) and G (66) have been
assigned the (S)-configuration at C-9, in contrast to the other modiolides (or most
ten-membered lactone natural products in general). The absolute configuration at C4 was determined as (R) for modiolide G (66), based on Mosher’s method, and from
there the absolute configurations at C-7 and C-9 were deduced to be the opposite of
those in modiolide A (61) [82].
3.2 Stagonolides and Curvulide A
Stagonolide A (85), originally named stagonolide, was first isolated and characterized
in 2007 by Yuzikhin et al. from culture filtrates of Stagonospora cirsii [87]. This
fungus is a pathogen that affects Cirsium arvense, the field or Canada thistle, a
perennial weed that is difficult to control in agriculture by mechanical means or with
common herbicides [88]. Stagonolide A (85) was shown to have strong phytotoxic
activity against C. arvense by inhibiting root growth and photosynthesis, and was
therefore proposed as a lead structure for novel herbicides derived from fungal plant
pathogens [87, 88] (Chart 2).
Shortly after this seminal investigation, several other ten-membered lactones
were isolated from Stagonospora cirsii, structurally characterized and tested for
their phytotoxic activity against C. arvense: stagonolides B–F (83, 86–89) [89] and
stagonolides G–I (90–92) [78] were discovered in 2008 by Evidente et al.; stagonolides J (93) and K (94), the most recent members of the stagonolide family, were
isolated in 2019 by Dalinova et al. [90]. The ten-membered lactone curvulide A
(95) has not been isolated from cultures of Stagonospora cirsii, but from the marine