Methylphosphonate analogues

Conventional intermediates based on m3>o-inositol have been adapted for the synthesis of methylphosphonate analogues of inositol phosphoric acids. Thus, 1.2,3,4,6-pentabenzoyl-myo-inositol was the. source (using reactions indicated in Scheme 25) of the 5-methylphosphonate (241) 3,6-di-O-benzyl-l, 2-O-isopropylidene-myo-inositol furnished the 4,5-bis(methylphosphonate) (242), and compound (44) yielded the... 

There has been interest in methylphosphonate analogues of intemucleotidic linkages. Work in this area in Stawinski s laboratory has been reviewed, together... 

The syntheses of a methylphosphonate analogue (86) of phosphatidylinositol together with its diastereomers as well as the methylphosphonate analogue (85) of myo-inositol-1-phosphate using the chiral myo-inositol derivative shown in Scheme 15 has been reported. ... 

Phosphonic acid analogues of aspartic acid, glutamicacid C-benzy1g1ycine,191 and the phosphor inane (70)1 92 have been studied, also the oxime (71)193 a phosphonopiperidinol - with a very distorted chair structure,194 the phosphonate (72),195 a pyrazole,196 a thiocarbamoy1phosphonate, 97 and two iminobis-(methylphosphonic acids).198 Additionally there have been studies of the new bicyclic sulphur heterocycle (73),199 the oxazaphospho1idine (74)200 and a triaminophosphetanium aluminium betaine.201... 

Sulfenyl chlorides and halogens react with 1,2-alkadienylphosphonic acids to afford phosphorus-containing heterocydes [72], However, the electrophilic addition of dialkyl 4-methyl-2,3,5-hexatrien-2-yl phosphonates with sulfenyl or selenyl chloride afforded 2-thienyl methylphosphonates or the seleno analogues [73, 74]. The conjugate addition of sulfenyl or selenyl chloride with the 2,4-diene moiety in the starting allene leads to the formation of the five-membered skeleton (Scheme 10.69). 

M. Minami, D.-M. Hui, M. Katsumata, H. Ina-gaki and C.A. Boulet, Method for the analysis of the methylphosphonic acid metabolites of sarin and its ethanol-substituted analogue in urine as applied to the victims of the Tokyo sarin disaster, J. Chromatogr., B, 695, 237-244 (1997). 

Preparation of the DHAP analogue, 4-hydroxy-3-oxobutylphosphonic acid, which is an effective donor substrate, is accomplished in four steps from glycidol.29 Glycidol is silyl protected then its epoxide is opened by dimethyl methylphosphonate. The secondary alcohol was oxidized under the Dess-Martin conditions. Deprotection of the alcohol followed by phosphate hydrolysis, generated the DHAP phosphonate analogue (Scheme 5.9). 

Ohta, H., Ohmori, T., Suzuki, S., Ikegaya, H., Sakurada, K., Takatori, T. (2006). New safe method for preparation of sarin-exposed human erythrocytes acetylcholinesterase using non-toxic and stable sarin analogue isopropyl p-nitrophenyl methylphosphonate and its application to evaluation of nerve agent antidotes. Pharm. Res. 23 2827-33. 

A scale-up synthesis of isosteric phosphonate analogue (178) of mannose-6-phosphate (M6P) has been perfonned via regioselective nucleophilic displacement of the protected 4,6-cyclic sulfate precursor (179) by lithiated dialkyl methylphosphonates in the key step. ... 

This year s nucleotide and nucleic acid literature has been dominated by interest in internucleoside linkages. A number of approaches to novel internucleoside linkages in dimers have been published in addition to stereoselective routes to phosphorothioate and methylphosphonate linkages. In some cases these studies have also extended to the oligonucleotide level. In addition a number of novel nucleotide analogues have been described. One of the most exciting areas in the field of nucleic acid chemistry is the application of in vitro selection techniques and these are reviewed for the first time. 

A chemoenzymatic synthesis of the P-a-methyl 2 -deoxynucleoside triphosphates 122 has been described which involves reaction of the 5 -0-(methylpho-sphonyl)-N-protected nucleosides with pyrophosphate in the presence of CDI. Removal of the base protection by treatment with penicillin amidase gave compounds 122 leaving the labile a-methylphosphonate intact. A number of 2 -deoxythymidine 5 -triphosphate and 3 -azido-2, 3 -dideoxythymidine 5 -tripho-sphate analogues (123) containing a hydrophobic phosphonate group have also been synthesised and evaluated as substrates for several viral and mammalian polymerases. Some y-ester (124) and y-amide (125) derivatives of dTTP and 3 -azido-2, 3 -dideoxythymidine 5 -triphosphate (AZTTP) were also synthesized and studied. The y-phenylphosphonate triphosphate 126 and its conjugation to biotin and fluorescein labels has also been described. 

Phosphorus nuclear magnetic shielding anisotropy in (1-hydroxyalkyl)dimethyl-phosphine sulfides has been studied using the IGLO method, and the tautomeric stability, molecular structure, and internal rotation of methylphosphonic dicyanide MeP(0)(CN)2, dicyanomethoxyphosphine MeOP(CN)2, and their isocyano analogues have been extensively followed using ab initio calculations. ... 

Phosphonylation of a -3-(9-isopropylidene-a -pyridoxyl chloride via a Michaelis-Becker reaction, followed by deprotection with 1 M HCl and oxidation of the resulting primary alcohol with MnOj, produces diethyl (4-fonnyl-3-hydroxy-2-methyl-5-pyridyl)methylphosphonate (Scheme 5.38), an analogue of pyridoxal 5 -phosphate whose 5-position side chain has been replaced by a phospho-nomethyl group. The alcohol oxidation step can be accomplished with a wide range of reagents, such as activated MnOj in CHCI3 at room temperature (53%), PCC in CH2CI2 (83-86%), or the Swem reaction (>95%). ... 

The vinylic and acetylenic analogues of pyridoxal 5 -phosphatc are known. The former can be prepared as a cis-trans mixture by Peterson reaction between a ,3-O-isopropylideneisopyridoxal and diethyl l-lithio-l-(trimethylsilyl)methylphosphonate. Isolation of the cis derivative and subsequent deprotection of the alcohol followed by oxidation with MnO2 in ("HCl, leads to the diethyl... 

Amino Acids and Peptides. - Wasserman s method of one-carbon homologation of carboxylic acids to give a-ketocarboxylates involves reaction with cyanomethylenetriphenyl-phosphorane followed by ozone (Scheme 24) and has been used as a key step in a chemo-enzymatic synthesis of isotopically labelled L-valine, L-isoleucine, and o/fo-isoleucine. Alkylation of the carbanion derived from the imino-substituted methylphosphonate diphenyl ester (186) with indol-3-ylmethyl bromide followed by appropriate deprotection has been used to prepare the phosphonate analogue (187) of tryptophan (Scheme 25). The deprotected analogue (188) and derived peptides show activity as inhibitors of chymotrypsin. Two approaches to solid phase Wadsworth-Enunons reactions which have applications in combinatorial chemistry have been reported. In one diethylphosphonoacetamide is bound to PEG-PAL resin via a peptide link, while... 

---