58
H. Zhu et al.
Table 18 seco-Aspochalasins
Compound
Origin
References
Pericoannosin A (434)
Periconia sp. F-31
[184]
Secochalasin A (435)
Aspergillus micronesiensis
[191]
Secochalasin B (436)
Aspergillus micronesiensis
[191]
Amiaspochalasin F (437)
Aspergillus micronesiensis
[189]
Amiaspochalasin G (438)
Aspergillus micronesiensis
[189]
2.4.1 Carbocyclic Aspochalasins
[5.6.11]-Aspochalasins and Related Derivatives
The first aspochalasins were aspochalasins A–D (343–346) (Table 15 and Fig. 15)
[156], which were discovered from the fungus Aspergillus microcysticus in 1979.
Their structures were elucidated by extensive spectroscopic studies and chemical
degradation. The skeleton and stereochemistry at C-17 and C-18 of aspochalasin C
(345) were then determined by X-ray diffraction analysis of its 17,18-di-O-acetyl
derivative [157], and aspochalasin D (346) was considered to be C-18 epimer of
aspochalasin C (343). In 2001, Hayakawa and coworkers re-isolated aspochalasin
D (346) from Aspergillus sp. AJ1 17509, and revised the previous stereochemical
assignment indicating that aspochalasin D (346) is the C-17 epimer of aspochalasin
C (343) [158].
Many aspochalasins have been found to possess additional functional groups
besides the normal structural modifications. Phomacin C (348) [160], which was
isolated from the fungus Phoma sp. in 1997, possesses a unique hydroxymethyl
substituent at C-16 that had not then been observed among other aspochalasins. In
2017, Yang and coworkers isolated six more aspochalasins with a hydroxymethyl
group at C-16 (376–381) [172] from the marine sediment-derived fungus Westerdykella dispersa, and determined the structure of 18-oxo-19,20-dihydrophomacin C
(376) by single-crystal X-ray diffraction.
Aspochalasins N (356) and O (357) [166], isolated from the fungus Spicaria
elegans, were obtained by employing the OSMAC approach via changing the culture
conditions. Both aspochalasin N (356) and O (357) possess an additional acetonyl
group at C-20, but whether they are naturally occurring products or not was not
discussed biosynthetically. Recently, overexpression of the transcription factor gene
phmR encoded in the phm gene cluster resulted in the production of a congener,
phomacin F (387) [173].
Aspochalasins V (366) and W (367) [170] were isolated from the culture broth of
Aspergillus sp., which was found in the gut of a marine isopod Ligia oceanica. Both
compounds are unusual as a methylthiol group was found to occur at C-20 of their
macrocyclic ring. This is the first report on methylthio-substituted aspochalasins, and
also on the first methylthio-substituted cytochalasans, which possibly are formed by
methylthiotransferases [181].
H. Zhu et al.
Table 18 seco-Aspochalasins
Compound
Origin
References
Pericoannosin A (434)
Periconia sp. F-31
[184]
Secochalasin A (435)
Aspergillus micronesiensis
[191]
Secochalasin B (436)
Aspergillus micronesiensis
[191]
Amiaspochalasin F (437)
Aspergillus micronesiensis
[189]
Amiaspochalasin G (438)
Aspergillus micronesiensis
[189]
2.4.1 Carbocyclic Aspochalasins
[5.6.11]-Aspochalasins and Related Derivatives
The first aspochalasins were aspochalasins A–D (343–346) (Table 15 and Fig. 15)
[156], which were discovered from the fungus Aspergillus microcysticus in 1979.
Their structures were elucidated by extensive spectroscopic studies and chemical
degradation. The skeleton and stereochemistry at C-17 and C-18 of aspochalasin C
(345) were then determined by X-ray diffraction analysis of its 17,18-di-O-acetyl
derivative [157], and aspochalasin D (346) was considered to be C-18 epimer of
aspochalasin C (343). In 2001, Hayakawa and coworkers re-isolated aspochalasin
D (346) from Aspergillus sp. AJ1 17509, and revised the previous stereochemical
assignment indicating that aspochalasin D (346) is the C-17 epimer of aspochalasin
C (343) [158].
Many aspochalasins have been found to possess additional functional groups
besides the normal structural modifications. Phomacin C (348) [160], which was
isolated from the fungus Phoma sp. in 1997, possesses a unique hydroxymethyl
substituent at C-16 that had not then been observed among other aspochalasins. In
2017, Yang and coworkers isolated six more aspochalasins with a hydroxymethyl
group at C-16 (376–381) [172] from the marine sediment-derived fungus Westerdykella dispersa, and determined the structure of 18-oxo-19,20-dihydrophomacin C
(376) by single-crystal X-ray diffraction.
Aspochalasins N (356) and O (357) [166], isolated from the fungus Spicaria
elegans, were obtained by employing the OSMAC approach via changing the culture
conditions. Both aspochalasin N (356) and O (357) possess an additional acetonyl
group at C-20, but whether they are naturally occurring products or not was not
discussed biosynthetically. Recently, overexpression of the transcription factor gene
phmR encoded in the phm gene cluster resulted in the production of a congener,
phomacin F (387) [173].
Aspochalasins V (366) and W (367) [170] were isolated from the culture broth of
Aspergillus sp., which was found in the gut of a marine isopod Ligia oceanica. Both
compounds are unusual as a methylthiol group was found to occur at C-20 of their
macrocyclic ring. This is the first report on methylthio-substituted aspochalasins, and
also on the first methylthio-substituted cytochalasans, which possibly are formed by
methylthiotransferases [181].