On the Stereochemistry of Fecapentaene-12

Kingston, David G. I.; Piccariello, T.; Duh, Chang‐Yih; Govindan, Serengolam V.; Wilkins, Tracy D.; Tassell, Roger L. Van; Gen, A. Van Der; Wit, P. P. De; Steeg, M. van der

doi:10.1021/np50055a032

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…Standardization of the mutagenic activity to the UV absorbance at 334 nm revealed that the major components all had similar mutagenic potencies. This observation is in agreement with recent reports that FP-12 isomers with at least one cis double bond are similar in mutagenic activity to all-trans-FV-12 (35,40). No mutagenic activity was associated with the early eluting compounds, which did not possess the FP-12 spectrum and represent the ultimate decomposition products.…”

Section: Resultssupporting

confidence: 92%

Decomposition and quality control considerations in biological work with fecapentaene preparations

Pj²,

Anjo³

et al. 1989

Chem. Res. Toxicol.

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Solutions of synthetic fecapentaene 12 (FP-12) intended for carcinogenicity studies were found to decompose extremely rapidly during customary dosage procedures. Apparent half-lives as short as 15 min were observed. While rates and even the qualitative course of decomposition were surprisingly variable in replicate experiments, high concentration and exposure to air were confirmed to be especially important destabilizing influences. The results suggested a primary role for a radical decomposition mechanism in the presence of atmospheric oxygen. Consistent with this hypothesis, FP-12 solutions were significantly stabilized by the radical chain-breaking antioxidant vitamin E. On the other hand, dithiothreitol greatly destabilized FP-12, presumably because of its nucleophilicity. The diacetyl diester of FP-12 was more soluble than the parent diol, but its decomposition rates in the presence and absence of vitamin E were similar to those of unesterified FP-12. Ultraviolet irradiation of an all-trans-FP-12 solution decreased its concentration by 70% in 0.5 min. The mutagenicities of the decomposition/isomerization products of FP-12, as studied in Salmonella typhimurium tester strain TA 100, ranged from negligible to comparable with all-trans-FP-12 itself. It is concluded that unchecked decomposition of fecapentaene preparations can profoundly affect biological tests therewith. While this can be largely controlled through the use of rigorous precautions, including protection from air, light, nucleophiles, and acids as well as selection of the lowest concentration compatible with the application at hand, the data argue strongly for inclusion of appropriate quality control measures in all future dosing operations to prove that the biological activity reported is that of the fecapentaene itself rather than that of a decomposed dosing solution.

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Section: Resultssupporting

confidence: 92%

Decomposition and quality control considerations in biological work with fecapentaene preparations

Pj²,

Anjo³

et al. 1989

Chem. Res. Toxicol.

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show abstract

“…A careful analysis of this spectrum, together with the spectra of synthetic 1 -E and 1 -Z isomers of fecapentaene-12, indicated that the natural product contains a small amount (around 10%) of a 1 -Z isomer (27). Further comparisons with synthetic materials (27,30) indicated that a major component of fecapentaene 12 has the all-E configuration, but that 5-Z, 1 -Z, and probably 3-Z components are also present.…”

Section: Introductionmentioning

confidence: 99%

“…The isolation of mutagens was still a challenging task, since they proved to be unstable to both air and acid, but the discovery of the stabilizing effect of butylated hydroxytoluene (BHT) on mutagen-containing solutions enabled us to circumvent the oxidation problem (22). A combination of chromatographic techniques then yielded a mutagen fraction which was originally thought to be homogeneous (24), but which was later shown to consist of a mixture of stereoisomers (25)(26)(27). Similar studies by the Toronto group, using pooled feces from several donors, yielded a similar mixture of mutagens and also a second mutagen which was shown to be a homologue of those in the first group (28,29).…”

Section: Introductionmentioning

confidence: 99%