Phosphono

HP(0)(0H)2 Phosphonic acid HP(0)d Phosphonoyl-—PiOfOHj Phosphono- Phosphonate... 

ANTTBIOTTCS - NUCLEOSIDES AND NUCLEOTIDES] (Vol 3) 2-(formylamino)-N-(5-0-phosphono-b-d-ribofuranosyl acetamide [349-34-8]... 

One of the simplest molecules found to inhibit the repHcation of DNA vimses in animals is phosphonoformic acid [4428-95-9] (PEA, 1) CH O P. Both PEA (as the trisodium salt CNa O P, foscamet [63585-09-1] audits homologue phosphono acetic acid [4408-78-0] (PAA, 2) C2H O P, were developed by Astra Pharmaceuticals (6) and show selective inhibition of DNA polymerase in various herpes vimses. 

Fig. 2. Enzyme catalysis by glycinaminde nbonucleotide transfomiylase (GAR TFase). (a) Transfer of the formyl group from (13) to (12) to form 2-(formylamino)-A/-(5-0-phosphono-P-D-ribofuranosyl acetamide [349-34-8] (14) and (b) multisubstrate inhibitor (15).

Gouaux, J.E., Lipscomb, W.N. Crystal structures of phosphonoacetamide ligated T and phosphono-acetamide and malonate ligated R states of aspartate carbamoyltransferase at 2.8 A resolution and neutral pH. Biochemistry 29 389-402, 1990. 

Davis has also employed a similar procedure for the synthesis of aziridine-2-phosphonoates, involving the addition of N-(2,4,6-trimethylphenylsulfinyl)imine to anions of diethyl a-halomethyl phosphonates (Scheme 1.29) [53, 54], Aziridines... 

Other common chemistries includes phosphonates, polymaleates, and phosphono- and phosphinopolycarboxylates. 

The reaction can be also carried out with butyrolactone leading to y-(dialkyl-phosphono)butyric acid esters [153,154]. 

Oleic acid, linolic acid, ricinolic acid, and 2-bromostearic acid methyl ester as well are reacting with diethyl phosphite in the presence of benzoyl peroxide to the corresponding phosphono fatty acid esters [156-158]. 

The prefix terms used for phosphate esters in organic nomenclature ([14], p.65) are 0-phosphono- and O-phosphonato- for the groups (H0)2P(0)- and (0 )2P(0)-respectively, bonded to oxygen. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Two heterocyclic phosphonates have been designed and synthesized in an attempt to identify more spatially conHned, planar analogs of glyphosate than obtained previously with the pyridine analog 111 (75). Molecular modeling experiments suggest that 5-phosphono-thiazolin-2-one 133 and 5-phosphono-l,2,4-triazolin-3-one 137 each may overlap either with glyphosate or its known competitive substrate, phosphoenolpyruvate (PEP), very well (5). 

The synthesis of 5-phosphono-l,2,4-triazolin-3-one 137 began with the low-temperature metalation and phosphorylation (77) of the f-butyldimethylsilyl (TBDMS)-protectedlV-benzyl-tiiazolinone 134. The phosphonate diester 135 was obtained ter the silyl protecting group... 

B 0 N P-l- Hydroxyethyl- phosphono-glycine Context dependent Context dependent [122-125]... 

In these a-phosphorylated dithioesters, the electron-withdrawing effect of the phosphono group, which strongly increases the electrophilic character of the thiocarbonyl group, makes the latter more prone to the thiophilic attack of nucleophiles and stabilizes the resulting carbanion. The main reactions of 1 with nucleophiles are summarized in Scheme 2. 

The method has then been efficiently used to remove selectively the exocycHc methylsulfanyl group from phosphorylated thiopyranyl derivatives 85 resulting from hetero Diels-Alder reaction of a phosphono-dithioformate or dithioacetate (see Sects. 2.1.2 and 2.2.3). FimctionaHzed thiopyrans 86 [17,18,27a] are thus obtained (Scheme 25). Owing to this selective desulfanylation, phospho-nodithioesters can be used as heterodienophiles in place of the corresponding phosphonothioaldehyde, not described so far and probably very unstable. 

Among /1-thiosubstituted organophosphorus compounds bearing chiral groups, phosphono methyl thiazolines (Sect. 2.2.1, Scheme 8) and o-sulfanyl aryl phos-phonamides or phosphinoxides (Sect. 3.3, schemes 20 and 21) have already been mentioned. As a complement to this, some recent synthesis of non racemic /1-sulfinyl phosphines and phosphonates and thiazolidinyl phosphonates are reported below. Moreover, some chiral )8-thio-substituted phosphines have been used as metal ligands in asymmetric catalysis and are listed in Sect. 5.3. 

Conversion of Carbonyl Croups and their 0,0- or 0,(V-Acetals into a-Halo, a-Azido, a-Alkinyl, and a-Phosphono Ethers... 

Bacillus cereus degrades (45) to acetaldehyde with fission of the C—P bond. An enzyme which catalyses the decomposition of phosphono-acetaldehyde (47), an intermediate in this degradation to acetaldehyde, has been characterized. The enzyme will only degrade (47) and will not breakdown a number of other phosphonates, including phosphonomycin (48). ... 

Prochiral 2-((o-phosphono)alkyl-1,3-propanediols 50 were enantioselec-tively acetylated to give the corresponding 0-acetyl derivatives 51 in very high yields and with high ees (Equation 27). °... 

Two types of racemic 3-hydroxy phosphonates, in which the phosphono and hydroxy moiehes are separated hy double bond, were successfully resolved using a common enzyme-catalysed acetylation. Both acyclic 52 (Equation 28) and cyclic 54 (Equation 29) derivatives underwent easy acetylation under the kinetic resolution conditions to give the products in high yield and with almost full stereoselechvity. 

Isolable pyrazolines (183) are obtained from the (1,3-butadiene)phosphonic acid esters (182 X=S02Me, COOalkyl R "=H or Me R2=Me or Ph) (products from (182 X=CN) are thermo-labile) and diazomethane. Pyrolysis of the phosphorylated pyrazolines affords phosphonopentadienes rather than phosphono-cyclopropanes (contrast (184)) and with NaH give pyrazoles or pyrazolephbsphonic acid esters. 

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