Pivaloyloxymethyl esters

Another synthesis avoids the isolation of 6-APA and starts directly with penidllin G. Reaction with chloromethyl pivalate gives its pivaloyloxymethyl ester. This reacts with PCI5 to an imidoyl chloride which may be solvolyzed with propanol. The add chloride of (R)-... 

ANTTBIOTTCS - BETA-LACTAMS - PENICILLINS AND OTTiERS] (Vol 3) -pivaloyloxymethyl ester derivative [CARBOXYLIC ACIDS - TRIALKYLACETIC ACIDS] (Vol 5)... 

Pivaloyloxymethyl Ester (POM-OjCR) (CH3)3CC02CH202CR The ester is prepared from the acid with PVOCH2I and Ag2C03 in DMF. ... 

Figure 6 Acyclic nucleoside phosphonates (ANPs) 9-(2-phosphonylmethoxy-ethyl)-adenine (PMEA) and -2,6-diaminopurine (PMEDAP), (R)-9-(2-phosphonyl-methoxypropyl)-adenine (PMPA) and -2,6-diaminopurine (PMPDAP), (5)-9-(3-fluoro-2-phosphonylmethoxypropyl)-adenine (FPMPA) and -2,6-diaminopurine (FPMPDAP), and the bis(pivaloyloxymethyl) ester of PMEA [Bis(pom)-PMEA].

Penicillin e.g., pivaloyl ester short-chain alkyl esters, e.g., methyl, ethyl, isopropyl, hydroxypropyl, and butyl esters Acyloxymethyl ester, e.g., pivaloyloxymethyl ester, 2,14,15... 

Annaert P, Kinget R, Naesens L, de Clercq E, Augustijns P (1997) Transport, uptake, and metabolism of the bis(pivaloyloxymethyl)-ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine in an in vitro cell culture system of the intestinal mucosa (Caco-2). Pharm Res 14 492-496. 

Miyauchi M, Kurihara H, Fujimoto K, Kawamoto I, Ide J, Nakao H. Studies on orally active cephalosporin esters. III. Effect of the 3-substituent on the chemical stability of pivaloyloxymethyl esters in phosphate buffer solution. Chem Pharm Bull 1989 37 2375-2378. 

More recently reported active esters are the different acyloxymethyl esters [129]. The pharmacology of penicillin G acetoxymethyl ester (Penamecillin) was investigated in 1966 [130]. A further derivative is the acetoxymethyl ester, or preferably the pivaloyloxymethyl ester, of am-... 

Crystals from methanol-acetone, tnp 156 (dec). [a) f + 285 Amdinocillin Pivoxil. therap CAT Antibacterial... 

Kurz T, Schlueter K, Kaula U, Bergmann B, Walter RD, Geffken D (2006) Synthesis and antimalarial activity of chain substituted pivaloyloxymethyl ester analogues of fosmidomycin and FR900098. Bioorg Med Chem 14 5121-5135... 

Kurz T, Behrendt C, Kaula U, Bergmann B, Walter RD (2007) a-Phenylethyl substituted bis (pivaloyloxymethyl) ester analogs of fosmidomycin and ER900098. Aust J Chem 60 154— 158... 

The acyclic nucleoside phosphonate, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), also known as Adefovir [1], can be considered as an analogue of (2 -deoxy)adenosine 5 -monophosphate ((d)AMP ) [2]. PMEA has excellent antiviral properties [1] and in the form of its bis(pivaloyloxymethyl)ester, Adefovir dipivoxil, it has recently been approved by the US Food and Drug Administration (FDA) for the treatment [3] of hepatitis B patients these people suffer from an infection of aDNAvirus. 

Fridland and coworkers have shown that the bis(pivaloyloxymethyl) esters of three acyclic nucleoside phosphonates, including PMEA, have improved antiviral activity and selectivity when compared with the corresponding phosphonic acid [65]. Using radiolabelled material, in cells the PMEA prodrug (47, R = Bu ) hydrolyzed rapidly to PMEA after which it was phosphorylated to the active diphosphate. In contrast, the prodrug had a half-life of over 24 h at pH 2,0, suggesting that it may be stable in gastric... 

When planning a biotransformation, identification of a bifunctional pro-chiral substrate provides a clear benefit over conventional resolution since up to 100% of a desired enantiomer can be obtained by enzymatic desymme-trization. This feature is exemplified in the work of Achiwa and coworkers [37] in the area of 1,4-dihydropyridine calcium channel blockers (Scheme 5.11). Hydrolysis of the bis(pivaloyloxymethyl)ester (15) gave enantiopure monoacid (16) which was used to correlate the absolute configuration of the novel agent (17) with that of (5)-(-)-felodipine (18). 

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