Synthesis and biological evaluation of a trichothecene epi-epoxide, 3α,4β,15-triacetoxy-12,13-epi-epoxytrichothec-9-ene

Colvin, Ernest W.; Cameron, Stuart

doi:10.1039/c39860001642

Cited by 10 publications

(11 citation statements)

References 2 publications

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“…The parent compound of trichothecenes, trichodiene ( Fig. In trichothecenes, specific oxygens such as the 12,13-epoxide have been shown to be required for toxicity (Colvin and Cameron 1986). 1) biosynthesis .…”

Section: Introductionmentioning

confidence: 99%

TheTri4 gene ofFusarium sporotrichioides encodes a cytochrome P450 monooxygenase involved in trichothecene biosynthesis

1995

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The Tri4 gene of Fusarium sporotrichioides was isolated from a cloned DNA fragment carrying the Tri5 gene by complementation of a Tri4- mutant. The nucleotide sequence of Tri4 was determined and the locations of three introns were identified. Analysis of Tri4 mRNA levels revealed that transcription reached maximum levels coincidently with the onset of trichothecene biosynthesis, and then declined 20-fold over the next 8 h. Disruption of Tri4 resulted in the loss of production of both trichothecenes and apotrichodiol and the accumulation of the unoxygenated pathway intermediate trichodiene. Transformants lacking a functional Tri4 gene were able to convert isotrichotriol, an early pathway intermediate, to T-2 toxin suggesting that most pathway enzymes are present in Tri4- mutants. These data suggest that the enzyme encoded by Tri4 catalyzes the first oxygenation step in the trichothecene pathway and participates in apotrichodiol biosynthesis. Tri4 encodes a protein of 520 residues (M(r) = 59 056) that shows significant homology with members of the superfamily of cytochromes P450. It appears most similar to the CYP3A subfamily (24.6% amino acid identity). Because it contains less than 40% positional identity with other cytochromes P450, the Tri4 gene has been placed in a new cytochrome P450 gene family designated CY P58.

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Section: Introductionmentioning

confidence: 99%

TheTri4 gene ofFusarium sporotrichioides encodes a cytochrome P450 monooxygenase involved in trichothecene biosynthesis

1995

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“…On the other hand, the 4-keto compound 19 was readily reduced by metal hydrides. The preparation of 4-epiverrucarol (20) started with the protection of the 15-OH group of verrucarol (21). Acetylation (Ac,O, pyridine, CH,C12) gave the monoacetate 22 in 63% yield.…”

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confidence: 99%

“…We planned to begin with the selective esterification of the 15-OH group with the verrucarinic-acid derivative 25 and accordingly to attach the muconic halfester 26 to the remaining 4-OH group. However, when 4-epiverrucarol (20) and 25 were submitted to the condensation procedure according to Neises y1amino)pyridine ((Me,N)Py), Et,N) [14], the reverse reactivity of the OH groups at C(4) and C(15) as compared to verrucarol (21) was observed. According to the 'H-NMR, the 4c( -monoacylated product 27 was formed as main product.…”

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confidence: 99%

“…Using Ac,O or AcCl in pyridine and CH,Cl,, the 4-OH group of 20 was slightly favoured. The 15-OH group of verrucarol (21) was predominately acetylated using Ac,O in pyridine, while AcCl in pyridine favoured the 4P-OH group [ 151. This procedure using Et,N instead of pyridine was also selective for the 15-OH group of 4-epiverrucar01 (20).…”

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confidence: 99%

“…All tested compounds also show immunosuppressive activity which points to a general cytotoxicity and not to a selective cytostatic or immunosuppressive activity. The presence of the 12,13-epoxy group has been shown to be essential for the biological activity of simple trichothecene esters [20] [21]. Verrucarin K ( = 12,13-deoxyverrucarin A), the first natural trichothecene lacking the 12,13-epoxy group, has been isolated some years ago [22].…”

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Synthesis of New unnatural Macrocyclic Trichothecenes: 4‐epiverrucarin A. 47th Communication on verrucarins and roridins

Jeker

Tamm

1988

Helvetica Chimica Acta

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~~~~~~ ~The 4-epiverrucarin A (24), a new unnatural macrocyclic trichothecene, was synthesized starting from 4-epiverrucarol(20). The latter was obtained by metal-hydride reduction of the 4-0x0 derivative 19. Subsequent conversion of 20 into the monoester 30 and then the diester 32 followed by macrolactonization of the latter yielded 4-epiverrucarin A (24). Attempts to invert the configuration of the naturally occuring 3a-OH group of a tricholhecene were unsuccessful. The cytostatic (P-8 15) and immunosuppressive (MLR) activity of several natural and unnatural trichothecenes was determined in v i m .Introduction. -In the preceeding communication [ 11, first results of our programme directed to the synthesis of new unnatural macrocyclic trichothecenes were described, namely the synthesis of 3-isoverrucarin (( 1"-0 )(4+3)abeo-verrucarin A; 1) and the two novel macrocyclic by-products verrucinol and verrucene (2). In continuation of these efforts, the next goal was the preparation of 3-and 4-hydroxytrichothecenes possessing unnatural configurations and to use them for the synthesis of additional macrocyclic analogues of verrucarin A (3). Such compounds will give more detailed information on the relationship between chemical structure and biological activity.

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ChemInform Abstract: Synthesis and Biological Evaluation of a Trichothecene epi‐Epoxide, 3α,4β,15‐Triacetoxy‐12,13‐epi‐epoxytrichothec‐9‐ene.

Colvin

Cameron

1987

ChemInform

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Synthesis and biological evaluation of a trichothecene epi-epoxide, 3α,4β,15-triacetoxy-12,13-epi-epoxytrichothec-9-ene

Cited by 10 publications

References 2 publications

TheTri4 gene ofFusarium sporotrichioides encodes a cytochrome P450 monooxygenase involved in trichothecene biosynthesis

TheTri4 gene ofFusarium sporotrichioides encodes a cytochrome P450 monooxygenase involved in trichothecene biosynthesis

Synthesis of New unnatural Macrocyclic Trichothecenes: 4‐epiverrucarin A. 47th Communication on verrucarins and roridins

ChemInform Abstract: Synthesis and Biological Evaluation of a Trichothecene epi‐Epoxide, 3α,4β,15‐Triacetoxy‐12,13‐epi‐epoxytrichothec‐9‐ene.

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