-
Reviews of Environmental Contamination... 2001DCP has been utilized as a soil fumigant for more than 45 yr for the control for parasitic plant nematodes. Injected into soil before planting of crops, the instability... (Review)
Review
DCP has been utilized as a soil fumigant for more than 45 yr for the control for parasitic plant nematodes. Injected into soil before planting of crops, the instability of DCP in soil and water and its volatility dictate the principal route of human exposure that may occur, inhalation. Extensive data have been accumulated on the toxicity and metabolism of DCP. DCP is moderately toxic via oral or inhalation exposure, is irritating to the skin and eyes, and has potential to produce skin sensitization. It is rapidly and extensively metabolized. It has a half-life in the blood of rats and humans of only 3-7 min and < 10 min, respectively. Rats and mice excrete approximately 80% of even relatively high oral dosages within 24 hr, primarily as breakdown products of a glutathione conjugate or as carbon dioxide. These products reflect the primary routes of metabolism of DCP, via GSH-conjugative and hydrolytic pathways. An additional pathway based upon the epoxidation of DCP has also been proposed, but this does not appear to occur to any toxicologically significant degree in the presence of normally occurring GSTs. Direct evidence of the latter pathway is only been obtained at dosages of DCP in excess of the reported LD50. Humans also appear to rapidly metabolize DCP and excrete its metabolites. Subchronic toxicity studies of relatively pure DCP in rats and mice via oral or inhalation routes have resulted in portal-of-entry tissue effects that reflect the irritant properties of this chemical to nasal and gastric mucosa. At higher exposure levels in mice, however, toxicity was also identified in a remote tissue, the urinary bladder. Toxicity in dogs ingesting DCP was limited to the formation of a regenerative hypochromic, microcytic anemia. No teratological or reproductive effects were observed in rats or rabbits inhaling DCP vapors. Nonneoplastic changes from chronic dosing of DCP were generally similar to those observed in subchronic studies. Somewhat variable responses, however, have been observed for neoplastic effects, depending on the DCP formulation, route, and species used. Inhalation of a recent formulation increased the benign tumor incidence in the lungs of male mice (only) while ingestion of similar test material by rats and mice resulted in a low incidence of benign liver tumors in rats (only). In contrast, an older formulation containing Epi as a stabilizing agent administered to rats and mice via bolus oral dosing induced a number of malignant or benign tumors: in the forestomach and liver in rats and the forestomach, lung, and urinary bladder in mice. An equally complicated database has accumulated for DCP in vitro and in vivo genotoxicity testing. Genotoxicity has been reported in in vitro assays; however, confounding factors such as low-purity formulations, use of a genotoxic stabilizer, or generation of reactive impurities during attempts to purify test material have complicated interpretation. DCP appears to lack direct DNA reactivity, and a general trend toward decreasing activity with increasing complexity of the assay system and the presence of GST is evident. The weight-of-evidence evaluation of the genotoxicity data base suggests a lack of genotoxicity in vivo. Clearly definable treatment-related effects of DCP suggesting a plausible nongenotoxic mechanism of tumorigenic action, for example, enhanced cell proliferation, have not been in evidence in target tissues of treated animals. Thus, the specific mode of tumorigenesis of DCP in test animals remains to be elucidated but appears to involve a non-DNA-reactive mechanism. In conclusion, DCP-based soil fumigants have maintained an important role in agricultural despite the structural similarity of DCP to known genotoxic carcinogens and its own activity in in vitro genotoxicity assays. This role results from a combination of its use on soils before the planting of crops, its limited environmental half-life, rapid metabolism by animals via GSH conjugation and catabolism to CO2, lack of genotoxicity in in vivo assays, and an extensive toxicological database in animals, including several oncogenicity bioassays. These data, when combined with occupational and environmental exposure information, have provided a scientifically sound basis for the continued safe use of DCP-containing products.
Topics: Allyl Compounds; Animals; Humans; Hydrocarbons, Chlorinated; Insecticides; Mammals; Molecular Structure
PubMed: 12882226
DOI: 10.1007/978-1-4613-0143-1_1 -
The Journal of Organic Chemistry Nov 2007Aiming to improve our understanding of the stability of radicals containing the allylic moiety, carbon-hydrogen bond dissociation enthalpies (BDEs) in propene,...
Aiming to improve our understanding of the stability of radicals containing the allylic moiety, carbon-hydrogen bond dissociation enthalpies (BDEs) in propene, isobutene, 1-butene, (E)-2-butene, 3-metylbut-1-ene, (E)-2-pentene, (E)-1,3-pentadiene, 1,4-pentadiene, cyclohexene, 1,3-cyclohexadiene, and 1,4-cyclohexadiene have been determined by quantum chemistry calculations. The BDEs in cyclohexene, 1,3-cyclohexadiene, and 1,4-cyclohexadiene have also been obtained by time-resolved photoacoustic calorimetry. The theoretical study involved a DFT method as well as ab initio complete basis-set approaches, including the composite CBS-Q and CBS-QB3 procedures, and basis-set extrapolated coupled-cluster calculations (CCSD(T)). By taking the C(sp3)-H BDE in propene as a reference, we have concluded that one methyl group bonded to C3 in propene (i.e., 1-butene) leads to a decrease of 12 kJ mol(-1) and that a second methyl group bonded to C3 (3-methylbut-1-ene) further decreases the BDE by 8 kJ mol(-1). When the methyl group is bonded to C2 in propene (isobutene), an increase of 7 kJ mol(-1) is observed. Finally, a methyl group bonded to C1 in propene (2-butene) has essentially no effect (-1 kJ mol(-1)). While this trend can be rationalized in terms of stabilization of the corresponding radical (through hyperconjugation and pi-delocalization), the BDE values observed for the dienes can only be understood by considering the thermodynamic stabilities of the parent compounds.
Topics: Allyl Compounds; Calorimetry; Models, Chemical; Quantum Theory; Thermodynamics
PubMed: 17924695
DOI: 10.1021/jo701397r -
IARC Monographs on the Evaluation of... 1995
Review
Topics: Allyl Compounds; Animals; Carcinogenicity Tests; Carcinogens; Humans; Insecticides
PubMed: 9097099
DOI: No ID Found -
The Journal of Chemical Physics Apr 2008The competition between rearrangement of the excited allyl radical via a 1,3 sigmatropic shift versus sequential 1,2 shifts has been observed and characterized using...
The competition between rearrangement of the excited allyl radical via a 1,3 sigmatropic shift versus sequential 1,2 shifts has been observed and characterized using isotopic substitution, laser excitation, and molecular beam techniques. Both rearrangements produce a 1-propenyl radical that subsequently dissociates to methyl plus acetylene. The 1,3 shift and 1,2 shift mechanisms are equally probable for CH(2)CHCH(2), whereas the 1,3 shift is favored by a factor of 1.6 in CH(2)CDCH(2). The translational energy distributions for the methyl and acetylene products of these two mechanisms are substantially different. Both of these allyl dissociation channels are minor pathways compared to hydrogen atom loss.
Topics: Allyl Compounds; Carbon; Computer Simulation; Free Radicals; Hydrogen; Models, Chemical; Models, Molecular; Molecular Conformation
PubMed: 18433182
DOI: 10.1063/1.2907714 -
Journal of the American Chemical Society Jul 2021The total synthesis of leiodermatolide A was accomplished in 13 steps (LLS). Transfer hydrogenative variants of three carbonyl additions that traditionally rely on...
Total Synthesis of Leiodermatolide A via Transfer Hydrogenative Allylation, Crotylation, and Propargylation: Polyketide Construction beyond Discrete Allyl- or Allenylmetal Reagents.
The total synthesis of leiodermatolide A was accomplished in 13 steps (LLS). Transfer hydrogenative variants of three carbonyl additions that traditionally rely on premetalated reagents (allylation, crotylation, and propargylation) are deployed together in one total synthesis.
Topics: Allyl Compounds; Hydrogenation; Molecular Conformation; Organometallic Compounds; Polyketides; Stereoisomerism
PubMed: 34237219
DOI: 10.1021/jacs.1c06062 -
Journal of the American Chemical Society Jun 2011The Pd-catalyzed cross-coupling of racemic tertiary allylic carbonates and allylboronates is described. This reaction generates all-carbon quaternary centers in a highly...
The Pd-catalyzed cross-coupling of racemic tertiary allylic carbonates and allylboronates is described. This reaction generates all-carbon quaternary centers in a highly regioselective and enantioselective fashion. The outcome of these reactions is consistent with a process that proceeds by way of 3,3'-reductive elimination of bis(η(1)-allyl)palladium intermediates. Strategies for distinguishing the product alkenes and application to the synthesis of (+)-α-cuparenone are also described.
Topics: Allyl Compounds; Catalysis; Dimerization; Palladium; Sesquiterpenes
PubMed: 21648464
DOI: 10.1021/ja2039248 -
The Journal of Organic Chemistry Apr 2019Alkoxyallylsiletanes are capable of highly chemo- and diastereoselective carbonyl allylsilylations. Reactive substrates include salicylaldehydes and glyoxylic acids....
Alkoxyallylsiletanes are capable of highly chemo- and diastereoselective carbonyl allylsilylations. Reactive substrates include salicylaldehydes and glyoxylic acids. Chemoselectivity in these reactions is thought to arise from a mechanism involving first exchange of the alkyoxy group on silicon with a substrate hydroxyl followed by activation of a nearby carbonyl by the Lewis acidic siletane and intramolecular allylation. In this way, substrates containing multiple reactive carbonyl groups (e.g., dialdehyde or triketone) can be selectively monoallylated, even overcoming inherent electrophilicity bias.
Topics: Aldehydes; Allyl Compounds; Glyoxylates; Silanes; Stereoisomerism
PubMed: 30811929
DOI: 10.1021/acs.joc.8b03028 -
Toxicological Sciences : An Official... May 2001Mechanistic data, when available, have long been considered in risk assessment, such as in the development of the nitrate RfD based on effects in a sensitive group... (Review)
Review
Mechanistic data, when available, have long been considered in risk assessment, such as in the development of the nitrate RfD based on effects in a sensitive group (infants). Recent advances in biology and risk assessment methods have led to a tremendous increase in the use of mechanistic data in risk assessment. Toxicokinetic data can improve extrapolation from animals to humans and characterization of human variability. This is done by the development of improved tissue dosimetry, by the use of uncertainty factors based on chemical-specific data, and in the development of physiologically based pharmacokinetic (PBPK) models. The development of the boron RfD illustrates the use of chemical-specific data in the improved choice of uncertainty factors. The draft cancer guidelines of the U.S. Environmental Protection Agency emphasize the use of mode of action data. The first choice under the guidelines is to use a chemical-specific, biologically based dose-response (BBDR) model. In the absence of a BBDR model, mode of action data are used to determine whether low-dose extrapolation is done using a linear or nonlinear (margin of exposure) approach. Considerations involved in evaluating a hypothesized mode of action are illustrated using 1,3-dichloropropene, and use of a BBDR model is illustrated using formaldehyde. Recent developments in molecular biology, including transgenic animals, microarrays, and the characterization of genetic polymorphisms, have significant potential for improving risk assessments, although further methods development is needed. Overall, use of mechanistic data has significant potential for reducing the uncertainty in assessments, while at the same time highlighting the areas of uncertainty.
Topics: Allyl Compounds; Animals; Boron; Dose-Response Relationship, Drug; Environmental Exposure; Forecasting; Formaldehyde; Humans; Hydrocarbons, Chlorinated; Nitrates; Reference Values; Risk Assessment; Risk Factors; Sensitivity and Specificity
PubMed: 11294971
DOI: 10.1093/toxsci/61.1.32 -
The Journal of Organic Chemistry Sep 2018Allylic Grignard reagents exhibit high reactivity and low selectivity in additions to carbonyl compounds. Additions of allylic Grignard reagents to carbonyl compounds...
Allylic Grignard reagents exhibit high reactivity and low selectivity in additions to carbonyl compounds. Additions of allylic Grignard reagents to carbonyl compounds were investigated using prenylmagnesium chloride as a mechanistic probe. When the carbonyl group is relatively unhindered, the addition proceeds through a six-membered transition state with allylic transposition. This process generally occurs with no diastereoselectivity because the reaction rates approach the diffusion limit. With hindered ketones, however, this pathway is disfavored, and the addition proceeds through a transition state resembling that of other Grignard reagents.
Topics: Allyl Compounds; Catalysis; Halogens; Ketones
PubMed: 30081634
DOI: 10.1021/acs.joc.8b01430 -
Organic Letters Aug 2004Diphenyldisulfone is a mild and efficient reagent for selective cleavage of methylprenyl (2,3-dimethylbut-2-en-1-yl), prenyl (3-methylbut-2-en1-yl), and methallyl...
Diphenyldisulfone is a mild and efficient reagent for selective cleavage of methylprenyl (2,3-dimethylbut-2-en-1-yl), prenyl (3-methylbut-2-en1-yl), and methallyl (2-methylallyl) ethers. These reaction conditions are compatible with the presence of other protecting groups such as acetals, acetates, and allyl, benzyl, and TBDMS ethers. Exposure of 2,3-dimethylbut-2-en-1-yl and 3-methylbut-2-en1-yl ethers to diphenyldisulfone led to the formation of 2,3-dimethylbuta-1,3-diene and isoprene, respectively. 2-Methylallyl ethers undergo isomerization to 2-methylpropenyl ethers, which are easily hydrolyzed into the corresponding free alcohols and isobutyraldehyde. [reaction: see text]
Topics: Alcohols; Allyl Compounds; Ethers; Indicators and Reagents; Sulfones
PubMed: 15281746
DOI: 10.1021/ol049135q