Other 1,3.5,7-Tetrazocines

The diethoxy derivative 4 can be transformed to the monolactame 5 by stirring an ethereal solution with silica gel, or used in substitution reactions to afford other derivatives, e g. JV,Ar,jV, jV -tetraethyl-4,8-dimethyl-l, 3,5,7-tetrazocine-2,6-diamine (6).23-24... 

Zhao J-S et al., Metabolism of octahydro-l,3,5,7-tetranitro-l,3,5,7-tetrazocine by Clostridium bifermentants strain HAW-1 and other several H2-producing fermentative anaerobic bacteria, FEMS Microbiol. Lett., 237, 65, 2004. 

Primary nitroaromatics are TNT the environmental breakdown products, including 1,3,5-trinitrobenzene (TNB), 1,3-dinitrobenzene (DNB), 2,4-and 2,6-dinitro-toluene (DNTs) and the primary reduction products 2-amino 4,6-dinitrotoluene and 4-amino 2,6-dinitrotoluene (ADNTs). Nitramines include RDX and octahydro-l,3,5,7-tetranitro-l,3,5,7-tetrazocine (HMX). Additional energetic compounds discussed in this chapter include nitroglycerin, white phosphorus, and ammonium perchlorate. Other energetic compounds are not discussed due to a lack of information regarding toxicity to wildlife species. 

One may mention the relative lack of information on the possible toxicity mechanisms of other groups of explosives. The administration of hexahydro-l,3,5-trinitro-l,3,5-triazine (RDX 30-300 mg kg-1 daily for 13 weeks) to rats caused hypotriglycidire-mia, convulsions, and death [4], In contrast, pentaerythritol tetranitrate (PETN 0.5%-1.0% in standard diet for 13 weeks) was nontoxic to rats [80], RDX was much less cytotoxic to V79 and TK-6 mammalian cell cultures than TNT [9], There also are very few data on their reactions with mammalian enzymes. Rabbit liver cytochrome P-450 2B4 (EC 1.14.14.1) converted RDX into 4-nitro-2,4-diazabutanal, two nitrite ions, ammonium, and formaldehyde, consuming one equivalent NADPH [81]. However, it is unclear whether this slow reaction (kcat < 0.01 s-1) may contribute to the toxicity of RDX. Xanthine oxidase transformed octohydro-l,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) at a lower rate, 10.5 nmol h 1 mg 1 protein under anaerobic conditions, into nitrite, formaldehyde, nitrous oxide, formic acid, and ammonium [82], Our preliminary observations show that RDX was much less reactive substrate for P-450R and E. cloacae NR than NTO or ANTA [53], Thus, the mechanisms underlying toxicity of RDX remain undisclosed. 

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