Phomactins, novel PAF antagonists from marine fungus Phoma sp.

Sugano, Michihiro; Sato, Aiya; Iijima, Yasuteru; Furuya, Kouhei; Haruyama, Hideyuki; Yoda, Keiko; Hata, Tadashi

doi:10.1021/jo00082a012

Cited by 100 publications

(34 citation statements)

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“…Within this series, phomactin D (24) was the most active, inhibiting the binding of PAF to its receptors and PAF-induced platelet aggregation with IC 50 values of 0.12 and 0.8 M, respectively. The structure-activity relationship of these compounds suggests that the conformation of the bicyclic ring system and the hydroxy group substitution patterns have significant effects on activity [110]. It is also interesting to note that sporulation of this Phoma sp.…”

Section: The Discovery Of New Anti-inflammatory Agentsmentioning

confidence: 94%

“…obtained from a crab shell. Subsequent large-scale fermentation (600 liters) followed by ethyl acetate extraction led to the isolation of the additional diterpenes phomactins B-G [110,111]. Within this series, phomactin D (24) was the most active, inhibiting the binding of PAF to its receptors and PAF-induced platelet aggregation with IC 50 values of 0.12 and 0.8 M, respectively.…”

Section: The Discovery Of New Anti-inflammatory Agentsmentioning

confidence: 99%

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Marine Microorganisms and Drug Discovery: Current Status and Future Potential

Jensen

Fenical²

2000

Drugs From the Sea

101

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Section: The Discovery Of New Anti-inflammatory Agentsmentioning

confidence: 94%

Section: The Discovery Of New Anti-inflammatory Agentsmentioning

confidence: 99%

Marine Microorganisms and Drug Discovery: Current Status and Future Potential

Jensen

Fenical²

2000

Drugs From the Sea

101

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“…11 The AC of (+)-verticillol (1) was indeed established by vibrational circular dichroism (VCD), 12 while the AC of some functionalized phomactins was confirmed by single crystal X-ray diffraction anomalous dispersion, 13 by the Mosher's method, and by electronic circular dichroism. 14 In contrast, the study of the AC of phomactatrienes has been scarcely explored perhaps because of the difficulties associated to the high volatility inherent to their hydrocarbon nature. Thus, the achievement of this task by VCD is highly desirable in order to strengthen the configurational scenario that supports the biosynthetic relationships of phomactatrienes with verticillanes, taxanes, and phomactins.…”

Section: Introductionmentioning

confidence: 99%

Absolute configuration of phomactatriene diterpenoids obtained by Wagner‐Meerwein rearrangement of epimeric verticillols

et al. 2019

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The epimeric diterpenes (+)‐(1S,3E,7E,11S,12S)‐verticilla‐3,7‐dien‐12‐ol (1), isolated from Bursera suntui, and (+)‐(1S,3E,7E,11S,12R)‐verticilla‐3,7‐dien‐12‐ol (2), isolated from Bursera kerberi, gave the same Wagner‐Meerwein rearrangement product (−)‐(1E,4Z,8Z,11S,12R)‐phomacta‐1,(15)4,8‐triene (3). The Et2O:BF3‐induced transformations evidence that verticillenes and phomactanes, both containing the bicyclo[9.3.1]pentadecane skeleton, are biogenetically related through the verticillen‐12‐yl cation (A+), which also is a key intermediate in the biosynthetic pathways to generate antitumor taxanes. Molecular modeling using the Monte Carlo protocol, followed by density functional theory (DFT) geometry optimization employing the hybrid functionals B3LYP and B3PW91, both with the DGDZVP basis set, secured the configuration of 3 as followed from the good agreement between the calculated and experimental vibrational circular dichroism spectra. Similar DFT calculations allowed determining the absolute configuration of (+)‐(1R,4R,5R,8S,9S,11S,12R,15R)‐1,15:4,5:8,9‐triepoxyphomactane (9), which surprisingly derives from epoxidation of the second minimum energy conformer of 3.

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“…The crystal structure is of low quality, but clearly showed the unusual ABCD-tetracyclic topology of (+)-phomactin A, and also determined the absolute stereochemistry. Subsequently, nine additional phomactins were isolated from various fungal sources with many of them displaying anti-PAF activity: 3–5 B, 3 B1, 3 B2, 3 C 3 [or Sch 47918 6 ], D, 3 E, 4 F, 4 G, 4 and finally, H 5 [Figure 2]. …”

Section: Introductionmentioning

confidence: 99%

Constructing the architecturally distinctive ABD-tricycle of phomactin A through an intramolecular oxa-[3+3] annulation strategy

Buchanan

Cole

et al. 2011

Tetrahedron

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Our efforts in constructing the ABD-ring of phomactin A through an intramolecular oxa-[3 + 3] annulation strategy is described. This struggle entailed finding a practical and efficient preparation of annulation precursor, and a realization of the unexpected competing regioisomeric pathway. The success entailed accessing the A-ring through Diels-Alder cycloaddition of Rawal’s diene. Furthermore, the discovery that the regioisomers from the annulation existed as atropisomers with respect to the D-ring olefin and that they could be equilibrated to the desired ABD-tricycle, allowing large quantities of tricycle to be accessed.

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Phomactins, novel PAF antagonists from marine fungus Phoma sp.

Cited by 100 publications

References 0 publications

Marine Microorganisms and Drug Discovery: Current Status and Future Potential

Marine Microorganisms and Drug Discovery: Current Status and Future Potential

Absolute configuration of phomactatriene diterpenoids obtained by Wagner‐Meerwein rearrangement of epimeric verticillols

Constructing the architecturally distinctive ABD-tricycle of phomactin A through an intramolecular oxa-[3+3] annulation strategy

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