Ethyl carbamate activation

Second-generation juvenoids incorporate more substantial stmctural departures from neotenin and are more resistant to metaboHc and environmental degradation. Epiphenonane, 2-ethyl-3-[3-ethyl-5-(4-ethylphenoxy)-pent-3-en-yl] 2-methyloxirane (131), has a rat oral LD q of 4000 mg/kg. It and similar juvenoids are used in China and Japan to prolong the last larval instar of the silkworm so that silk production is increased 10—15%. Fenoxycarb, ethyl [2-(4-phenoxyphenoxy)ethyl] carbamate (132) (mp 53°C, vp 0.0078 mPa at 20°C), is soluble in water to 6 mg/L. The rat oral LD q is >16,800 mg/kg. Fenoxycarb has a wide spectmm of activity, interfering with the developmental processes of fleas, cockroaches, and ants. 

Lin, A. J. Shansky, C. W. Sartorelli, A. C. Potential bioreductive alkylating agents. 3. Synthesis and antineoplastic activity of acetoxymethyl and corresponding ethyl carbamate derivatives of benzoquinones. J. Med. Chem. 1974, 17, 558-561. 

Very reactive nitrogen mustards and aziridine-containing molecules are usually too toxic for general therapeutic use, but find use in neoplastic disease. Benzodepa (182) is such an agent. Treatment of ethyl carbamate with phosphorous pentachloride leads to cyanate 180 which readily adds benzyl alcohol to produce carbamate 181. Displacement of the active... 

Miller JA, Miller EC. The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens recent results with ethyl carbamate and the spice flavors safrole and estragole. Br J Cancer 1983 48(1) 1-15. 

Compounds in this dibenzocycloheptene series also manifest antidepressant activity when the trigonal one-carbon bridge is replaced by tetrahedral carbon. Thus, the reaction of hydrocarbon (24-7) with a metal amide in liquid ammonia leads to the corresponding carbanion (29-1). Treatment of that with the ethyl carbamate from A -methyl-3-chloropropylamine (29-2) leads to the alkylation product. The carbamate protecting group is then removed by sequential saponification with a base followed by acidification. This yields the antidepressant agent protriptyline (29-3) [30]. 

ZimmerU, B., Schlatter, J. (1991). Ethyl carbamate analytical methodology, occurrence, formation, biological activity and risk assessment. Mutat. Res., 259, 325-350. 

Kobashi, K. (1992) Urease activity of /fe/Zcobacterpytor/. /. Clin. Pathol.. 45.367-368. Urechollne " bethanechol chloride, urethane inn (ethyl carbamate ethyl aminoformate ethyl urethane NSC 746) was formerly used clinically as a HYPNOTIC, and can be used as a GENERAL ANAESTHETIC in small animals. It has been used as an anticanCER agent in treating chronic myeloid leukaemia. 

Schmiedberg (1886) first reported that urethane (ethyl carbamate) produces rapid and deep narcosis in dogs. (The drug was subsequently used as a veterinary anesthetic.) More alkyl esters were soon introduced as hypnotics or anesthetics. For example, hedonal, which is more active than urethane, was introduced by Dreser7 (1899) as a fixed anesthetic for intravenous use. Figure 12-10, illustrates some early compounds, such as urethane and hedonal, which are only of historical interest, along with several others that, while still available, are rarely used in the United States. 

Ethyl N-[2-(p-phenoxyphenoxy)ethyl]carbamate (Ro 13-5223, fenoxycarb, 56), a compound possessing high juvenile hormone activity, has gained practical importance in the control of various lepidopterous species, scale insects, fire ants and stored product pests (Fischer eta/., 1980 Masnere/a/., 1981 Dome/a/., 1981). It completely inhibits the population growth of the California red scale, Aonidiella aurantii in a concentration as low as 0.03%. It interrupts the development during morphogenesis and thus prevents eclosion of adults. 

Although the role of cytochrome P450 in the metabolism of carbofuran has not been explored in any system, the metabolism of ethyl carbamate by P450 2EI has been reported by Lee elal. (1998). The study implicated cytochrome P450 2EI and carboxylcsterase enzyme in the metabolism of carcinogens such as ethyl carbamate in the murine liver microsomal system. The fish taken from a lake in Newfoundland with a history of hydrocarbon pollution showed increased AHH activity (Payne and Penrose, 1975). Thus, many workers have studied the EROD activity of fish in laboratory conditions or naturally exposed samples as a molecular biomarker for aquatic pollution. These studies are reviewed by Whyte etal. (2000) and Goldfarb el al. (1998), In addition, EROD activity in carbofuran-lreated fish has been measured in laboratory conditions. 

Urea is assayed using urease, and ammonium carbonate is formed. Wine contains less than 1 mg/1, and it is certainly of microbial origin. Urea is significant in winemaking as it may be a precursor of ethyl carbamate. In spite of certain reservations, L Office International de la Vigne et du Vin (OIV) authorize the treatment of wines by active urease in an acid medium. This enzyme is extracted from Lactobacillus fermentum. The objective is to reduce excessive urea concentrations in wine to avoid the formation of ethyl carbamate as the wine ages. 

Secondary alkyl carbamates, such as the 0-isopropyl or the 0-cyclohexyl derivatives coiild not be deprotonated. However, the optically active l-(trimethyl-silyl)ethyl carbamate 73 reacts smoothly and is substituted with overall retention of configuration [Eq. (24)] [56]. 

Conversely, antimutagenic activity of pepper was observed in the somatic mutation and recombination test in Drosophila melanogaster treated with the promutagen agent ethyl carbamate. Pepper was not effective, however, in inhibiting mutation events induced by the alkylating agent methyl methanesulfonate (El Hamss et al. 2003). 

---