Pivaloyloxymethyl

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)... 

Fluorenylmethyl, 387 Methoxymethyl, 388 Methylthiomethyl, 389 Tetrahydropyranyl, 390 Tetrahydrofuranyl, 390 Methoxyethoxymethyl, 390 2-(Trimethylsilyl)ethoxymethyl, 391 Benzyloxymethyl, 391 Pivaloyloxymethyl, 391 Phenylacetoxymethyl, 392 Triisopropylsilylmethyl, 392 Cyanomethyl, 392 Acetol, 393 Phenacyl, 393... 

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

Bj Pivaloyloxymethyl D(—)-Ot-aminobenzylpenicillinate. hydrochloride To a solution of pivaloyloxymethyl D(—)-a-azidobenzylpenicillinate (prepared as described above) in ethyl acetate (75 ml) a 0.2 M phosphate buffer (pH 2.2) (75 ml) and 10% palladium on carbon catalyst (4 g) were added, and the mixture was shaken in a hydrogen atmosphere for 2 hours at room temperature. The catalyst was filtered off, washed with ethyl acetate (25 ml) and phosphate buffer (25 ml), and the phases of the filtrate were separated. The aqueous phase was washed with ether, neutralized (pH 6.5 to 7.0) with aqueoussodium bicarbonate, and extracted with ethyl acetate (2 X 75 ml). To the combined extracts, water (75 ml) was added, and the pH adjusted to 25 with 1 N hydrochloric acid. The aqueous layer was separated, the organic phase extracted with water (25 ml), and the combined extracts were washed with ether, and freeze-dried. The desired compound was obtained as a colorless, amorphous powder. 

Prednisolone 21 -trimethylacetate pivaloyloxymethyl 6-aminopenicillanate tosylate (CjiHjoNjOgSj 25031-03-2) see Pivmecillinam podophyllotoxin... 

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... 

Pivoxil hydrochloride (miconazole pivaloyloxymethyl chloride) Micomax, Pivaanazolo [4]. 

Synthesis and in vitro evaluation of a phosphonate prodrug Bis(pivaloyloxymethyl) 9-(2-phosphonyl-methoxyethyl)adenine, Antiviral Res. 19 267 (1992). 

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. 

The short chain fatty acids include butyrate derivatives Hke phenylbu-tyrate, AN-9 (pivaloyloxymethyl butyrate) and valproate. Unfortimately, these compounds have poor potency and pharmacokinetic properties, including short half-life. Numerous Phase I studies with phenylbutyrate, in various oral and intravenous schedules [118-120] have been performed, with neurological toxicity at higher doses being reported. AN-9 showed initial promise in a Phase I study, where the MTD was not reached [121]. The subsequent Phase II study in nonsmall cell lung cancer in 47 patients resulted in fatigue, nausea and dysgeusia as common toxicities. Three partial responses (PR)... 

A -Benzyl groups on pyrimidinones and quinazolinones are removable by hydrogenolysis, although it is now more common to use a PMB substituent that can be removed with either TFA or CAN. Other N-protecting groups to be commonly used include benzyloxymethyl (BOM), removable by hydrogenation, ferZ-butoxycarbonyl (BOC), removable by anhydrous acid, and pivaloyloxymethyl (POM), which is removable by methanolic ammonia at room temperature. Alkenyl pyrimidinones have been employed in 1,3-dipolar cycloaddition reactions to prepare heterocyclic nucleotides. 

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. 

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