6346-15-2

Upstream product

• 67-56-1 methanol 
• 1983-26-2 chloromethylphosphonic dichloride 
• 89982-10-5 (+)-(R)-ethyl S-methyl chloromethylphosphonothioate 
• 3315-60-4 methanolate 
• 89982-13-8 Chloromethyl-phosphonothioic acid O,S-dimethyl ester 
• 75-87-6 chloral 

Downstream Products

• 114425-59-1 p-tolyloxymethyl-phosphonic acid monomethyl ester 
• 98491-12-4 (2,4-dichloro-phenoxymethyl)-phosphonic acid monomethyl ester 
• 115880-91-6 (E)-diphenyl 1-chloro 1,2-propenylphosphine oxide 
• 115880-92-7 (Z)-diphenyl 1-chloro 1,2-propenylphosphine oxide 
• 406502-76-9 dimethyl (S_S,1S,2R)-(+)-1-chloro-2-phenyl-2-(p-toluenesulfinamide)-ethylphosphonate 
• 406502-75-8 dimethyl (S_S,1S,2R)-(+)-1-chloro-2-(p-methoxyphenyl)-2-(p-toluene-sulfinamide)-ethylphosphonate 
• 511544-63-1 dimethyl (S_s,1S,2R)-(-)-1-chloro-2-(4-nitrophenyl)-2-(p-toluenesulfinamido)ethylphosphonate 
• 511544-67-5 dimethyl (S_s,1S,2R)-(+)-1-chloro-2-(4-trifluoromethylphenyl)-2-(p-toluenesulfinamido)ethylphosphonate 

Relevant academic research and scientific papers

Synthesis of a phosphonate-linked aminoglycoside-coenzyme a bisubstrate and use in mechanistic studies of an enzyme involved in aminoglycoside resistance

Aminoglycoside N-6′-acetyltransferases (AAC(6′)s) are important determinants of antibiotic resistance. A good mechanistic understanding of these enzymes is essential to overcome aminoglycoside resistance. We have previously reported the synthesis of amide- and sulfonamide-linked aminoglycoside-coenzyme A conjugates, which were useful mechanistic and structural probes of AAC(6′)s. We report here the synthesis of a phosphonate-linked aminoglycoside-coenzyme A variant, which is expected to be a superior mimic of the tetrahedral intermediate proposed for catalysis by AAC(6′)s. This synthetic target is especially challenging for a number of reasons, including the presence of multiple functional groups, the water solubility of both starting materials, and incompatibility of PIII chemistry with water. We have overcome these challenges by adding the expensive coenzyme A in the last step by means of an elegant Michael-type addition onto a vinylphosphonate in water. Overall, a single protection step was needed. The decreased inhibitory potency of this bisubstrate compared to that of the amide-linked analogue suggests that Enterococcus faecium AAC(6′)-Ii may not stabilize the proposed tetrahedral intermediate, and may act mainly through proximity catalysis.

Asymmetric synthesis of aziridine 2-phosphonates from enantiopure sulfinimines (N-sulfinyl imines). Synthesis of α-amino phosphonates

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure sulfinimines, has been developed for the asymmetric synthesis of aziridine 2-phosphonates. Best results involve cyclization of the syn and anti diastereomeric

2H-Azirine 3-phosphonates: a new class of chiral iminodienophiles. Asymmetric synthesis of quaternary piperidine phosphonates.

[reaction: see text] Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphonates and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts that on hydrogenation afford the first examples of enantiopure quaternary pip

Chiral Mono-, Di, and Tri-chloromethylphosphonates and Phosphonothioates: Preparation, Absolute Configuration, and the Stereochemical Course of Their Reaction with Methoxide

Enantiomerically pure (+)-(R)-O-ethyl S-methyl dichloromethylphosphonothioate, prepared using (-)-ephedrine as a chiral template, is futher chlorinated to the trichloro analogue using BunLi-CCl4 and dechlorinated by hydrogenolysis via the monochloro analogue to the corresponding methyl-phosphonothioate of known configuration.With methoxide, the trichloro derivatives gives P-C bond cleavage with inversion and the dichloro derivatives gives P-S bond cleavages with retention of configuration.In the monochloroderivative P-S and P-O bond cleavages are competitive, P-S bond cleavage occuring with 70percent inversion.Under similar reaction conditions P-S bond cleavage occurs stereospecifically with inversion of configuration in methylphosphonothioates.Methoxide treatment of (+)-(R)-ethyl isopropyl trichloromethylphosphonate results in P-C bond cleavage with inversion while (-)-(S)-ethyl phenyl dichloromethylphosphonate loses the OPh group also with inversion.Possible reaction mechanisms are discussed.

THE STEREOCHEMICAL COURSE OF SUBSTITUTION REACTIONS AT HALOMETHYLPHOSPHONATES

The stereochemistry of substitution at dihalomethylphosphonothioates is the same as for phosphorothioates whereas that for monohalomethylphosphonothioates is similar to the unsubstituted phosphonothioates.