Progress in the Chemistry of Cytochalasans
19
C-13 oxidized to an epoxy group (49) [40]. Besides the double bond at C-13, most of
[5.6.11]-cytochalasins have an additional double bond at C-19; however, some may
be oxidized to an epoxy (48–53) [40] or hydroxy group (35 and 40) [37–39], or even
become reduced (39) [38]. Cytochalasin J 2 (77) [50] is the only example from this
group with three double bonds in ring C, and the additional double bond at C-17 is
possibly formed by dehydration of the hydroxy group at C-18.
The C-21 carbons of all [5.6.11]-cytochalasins are oxidized and most of them
are oxygenated sp
3 carbons, with these examples being carbonyl carbons (33–47
and 57–60). Additionally, oxidations occur normally at C-17 and C-18. Acylation is
also an important aspect for the structural diversity of cytochalasins and normally, it
occurs on C-21. Cytochalasin D monoacetate (4) is the only representative with an
additional acetyl at C-7 [23]. It is not clear whether these acetylations are catalyzed
by BGC (Biosynthetic Gene Cluster) enzymes or not. The modification of rings B
and C for other groups of cytochalasans are similar to those of the cytochalasins.
• Skeleton reconstruction
Cytochalasin D1 (81) and cytochalasin C1 (82) [56], isolated from the liquid fermentation of fungus Xylaria cf. curta by Liu and coworkers, possess a unique 11membered macrocycle with an oxygen bridge between C-13 and C-20, forming
an unusual 12-oxabicyclo[6.3.1]dodecane core.
Phomopchalasins A (91) and B (88), two novel cytochalasins, were isolated from
the endophytic fungus, Phomopsis sp. shj2, derived from Isodon eriocalyx var. laxiflora, by Pu and coworkers [54]. Both these compounds stand out from this group as
they exhibit unexpected [5.6.5.8] and [5.6.6.7] ring systems, respectively, which are
possibly derived from normal [5.6.11] cytochalasins by means of additional cyclization. Subsequently, three more cytochalasins with [5.6.5.8] and [5.6.6.7] ring systems
were reported, including cytochalasin J 3 (89), xylastriasan A (90), and cytochalasin
H 2 (92) from Phomopsis sp. (CMB-M0042F) or Xylaria striata [50, 58]. Cytochalasin J 3 (89) could also be obtained from its precursor cytochalasin J (10) by an
acid-mediated conversion [50], suggesting that these compounds may be artifactual
in origin rather than actual natural products.
In recent years, additional cytochalasins possessing unusual ring systems (93–
101) have been isolated. Chaetoconvosins A (93) and B (94) [59], with an unprecedented 6/6/5/5/7 pentacyclic ring system, were obtained from the wheat rhizospheric
fungus Chaetomium convolutum cib-100. Their structures were elucidated on the
basis of the analysis of their spectroscopic data and by X-ray crystallography. In the
literature, the authors proposed a biosynthetic pathway starting from a phenylacetic
acid unit, which enabled the construction of the six-membered ring A first with
malonyl-CoA, and then by reaction with a PKS enzyme followed by Diels–Alder
cyclization, Michael addition, and further modifications, to form a 6/6/5/5/7 ring
system [59]. However, the present authors consider it would be more likely to afford
chaetoconvosins A (93) and B (94) from cytochalasins such as phomopchalasin A
(91) [54] and cytochalasin H 2 (92) [50] by means of ring A expansion, considering
cytochalasins are normally biosynthesized from an amino acid via PKS-NRPS hybrid
19
C-13 oxidized to an epoxy group (49) [40]. Besides the double bond at C-13, most of
[5.6.11]-cytochalasins have an additional double bond at C-19; however, some may
be oxidized to an epoxy (48–53) [40] or hydroxy group (35 and 40) [37–39], or even
become reduced (39) [38]. Cytochalasin J 2 (77) [50] is the only example from this
group with three double bonds in ring C, and the additional double bond at C-17 is
possibly formed by dehydration of the hydroxy group at C-18.
The C-21 carbons of all [5.6.11]-cytochalasins are oxidized and most of them
are oxygenated sp
3 carbons, with these examples being carbonyl carbons (33–47
and 57–60). Additionally, oxidations occur normally at C-17 and C-18. Acylation is
also an important aspect for the structural diversity of cytochalasins and normally, it
occurs on C-21. Cytochalasin D monoacetate (4) is the only representative with an
additional acetyl at C-7 [23]. It is not clear whether these acetylations are catalyzed
by BGC (Biosynthetic Gene Cluster) enzymes or not. The modification of rings B
and C for other groups of cytochalasans are similar to those of the cytochalasins.
• Skeleton reconstruction
Cytochalasin D1 (81) and cytochalasin C1 (82) [56], isolated from the liquid fermentation of fungus Xylaria cf. curta by Liu and coworkers, possess a unique 11membered macrocycle with an oxygen bridge between C-13 and C-20, forming
an unusual 12-oxabicyclo[6.3.1]dodecane core.
Phomopchalasins A (91) and B (88), two novel cytochalasins, were isolated from
the endophytic fungus, Phomopsis sp. shj2, derived from Isodon eriocalyx var. laxiflora, by Pu and coworkers [54]. Both these compounds stand out from this group as
they exhibit unexpected [5.6.5.8] and [5.6.6.7] ring systems, respectively, which are
possibly derived from normal [5.6.11] cytochalasins by means of additional cyclization. Subsequently, three more cytochalasins with [5.6.5.8] and [5.6.6.7] ring systems
were reported, including cytochalasin J 3 (89), xylastriasan A (90), and cytochalasin
H 2 (92) from Phomopsis sp. (CMB-M0042F) or Xylaria striata [50, 58]. Cytochalasin J 3 (89) could also be obtained from its precursor cytochalasin J (10) by an
acid-mediated conversion [50], suggesting that these compounds may be artifactual
in origin rather than actual natural products.
In recent years, additional cytochalasins possessing unusual ring systems (93–
101) have been isolated. Chaetoconvosins A (93) and B (94) [59], with an unprecedented 6/6/5/5/7 pentacyclic ring system, were obtained from the wheat rhizospheric
fungus Chaetomium convolutum cib-100. Their structures were elucidated on the
basis of the analysis of their spectroscopic data and by X-ray crystallography. In the
literature, the authors proposed a biosynthetic pathway starting from a phenylacetic
acid unit, which enabled the construction of the six-membered ring A first with
malonyl-CoA, and then by reaction with a PKS enzyme followed by Diels–Alder
cyclization, Michael addition, and further modifications, to form a 6/6/5/5/7 ring
system [59]. However, the present authors consider it would be more likely to afford
chaetoconvosins A (93) and B (94) from cytochalasins such as phomopchalasin A
(91) [54] and cytochalasin H 2 (92) [50] by means of ring A expansion, considering
cytochalasins are normally biosynthesized from an amino acid via PKS-NRPS hybrid