- (E)-(Hydroxyimino)(hydroxymethoxyphosphinyl)acetic Acid: Synthesis and pH-Dependent Fragmentation
-
In contrast to both its parent "troika" acid (E-1, a phosphorylating agent at pH 7 and 25 deg C) and its C-methyl isomer (E-2, which is stable at both acidic and neutral pH), (E)-(hydroxyimino)(hydroxymethoxyphosphinyl)acetic acid E-3 was unreactive at pH 7 and 25 deg C but at pH 1.5 fragmented to methyl phosphate 10 (15percent) and methyl phosphorocyanidate 11 (85percent).The minor product is consistent with solvent phosphorylation, the reaction exclusively observed with E-1.The non-phosphorylating fragmentation pathway is proposed to involve a preliminary E -> Z isomerization of 3 prior to Cα-Cβ cleavage.Dual fragmentation pathways were also detected (31P NMR) when the DCHA+ salt of E-3 (E-9) was heated in acetonitrile or EtOH; in addition to phosphorylation products (16-19percent), 11 was formed (81-84percent).Reaction of E-9 in refluxing EtOH:t-BuOH (1:1) showed low stereoselectivity in product formation (ca. 3:1 ethyl methyl phosphate : t-butyl methyl phosphate), supporting a dissociative phosphorylation process.
- Kashemirov, Boris A.,Fujimoto, Mari,McKenna, Charles E.
-
-
Read Online
- Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation
-
Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy.The decomposition of those substrates in D2O and in D2O-pyridine-d5 was studied to elucidate the mechanism of their alkylating reactivity.The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions.Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles.The first pathway deactivates the substrate with respect to the alkylating reactivity.Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.
- Roux, Charlotte le,Modro, Agnes M.,Modro, Tomasz A.
-
p. 3832 - 3839
(2007/10/02)
-
- Monomeric Methyl Metaphosphate: Reactions with Carbonyl Groups
-
Monomeric methyl metaphosphate, generated by fragmentation of methyl hydrogen erythro-1-phenyl-1,2-dibromopropylphosphonate in the presence of 2,2,6,6-tetramethylpiperidine, can be identified by its electrophilic attack on the aromatic rings of substituted anilines.The aromatic substitution reactions are quenched by pyridine, acetonitrile, dioxane, and dimethoxyethane but not by chloroform.Monomeric methyl metaphosphate attacks acetophenone to yield an enol phosphate; it converts a mixture of o-trifluoromethylaniline and acetophenone into N-(1-methylbenzylidene)-2-aminobenzotrifluoride and also converts aniline and ethyl benzoate into O-ethyl-N-phenylbenzimidate.These latter reactions mimic enzymatic reactions that require ATP.These facts introduce the possibility that ATP plays a kinetic role as well as a thermodynamic one in metabolic processes.
- Satterthwait, Arnold C.,Westheimer, F. H.
-
p. 4464 - 4472
(2007/10/02)
-