Penicillin esters

Deprotection. Treatment with AlClj leads to selective cleavage of an isopropyl aryl ether without affecting a coexisting methoxy substituent. A combination with ethanethiol is effective for the deprotection of p-methoxybenzyl ethers. Penicillin esters attached to... 

Preparation and properties of some phenoxymethyl penicillin esters,including the methyl ester, was the subject of a recent study 131. 

Reaction of penicillin esters 137 with CBT causes the cleavage of thia-zolidine ring to form olefins 138 via intermediate benzotriazoyl derivatives. With excess CBT the olefins 138 are formed directly (72CCA423) (Scheme 131). 

The unsubstituted sulfilimine analog of penicillin sulfoxide (373) is unknown however, reaction of the penicillin ester (374) with cyanon-itrene generated by the action of iodobenzene diacetate on cyanamide yielded the Af -cyanosulfilimine (375) (Kemp et al., 1979). Attempts to rearrange 375 to the deacetoxycephem failed. Oxidation of this sulfilimine... 

An alternative synthesis of the sulhlimine by reaction of the penicillin (383) with ethyl azidoformate resulted in the azetidinone (384) in low yield (Numata et al., 1972). This product was probably the result of an electrocyclic rearrangement of the intially formed sulfilimine (385). Conversion of 385 to a deacetoxycephem (290) was accomplished by heating in the presence of an acid catalyst. An analogous ring opening reaction was also observed on thermal treatment of the penicillin ester with dimethyl diazomalonate in the presence of cupric sulfate as catalyst. The initially formed ylide (386) proceeded to rearrange in an electrocyclic manner to afford the azetidinone (387) in good yield (Numata et al., 1972). 

The Cl spectra of all the penicillin esters gave an MH ion and showed a base peak at m/e 174 arising from a 2+2 / cycloreversion reaction (Fig. 5). These two peaks provide ready... 

Acyclic sulphides handled during a continuing study of the reactions of penicillins and cephalosporins are the result of reaction of methyl fluorosulphonate, methyl chloroformate, and acetyl chloride with penicillin-derived thiazine S -oxides. 4-Methylthioazetidinones formed by treatment of penicillin esters with Mel and strong base suffer replacement of the MeS group by acetoxy on treatment with Pb(OAc)4. The MeS group turns up unexpectedly on the... 

A simple and direct preparation of novel 6-a-acylamino-penicillins has been reported. The reaction of a penicillin ester (1 b,v) with A -chloro-A -sodio-urethane gave (30 b,v) in 80—90% yield. Oxidation of (30) to its sulphoxide and... 

Sulphenyl Halides.—Sulphenyl chlorides are readily available by chlorinolysis of disulphides, and this remains the most commonly used method of synthesis. Chlorinolysis of penicillin esters gives the sulphenyl chloride, and a route to an azetidinone sulphenyl chloride has been devised in which the relatively unstable sulphenic acid produced by penicillin sulphoxide pyrolysis is treated with SOCh in CCl, to give [43 R =C1, R =CH(C02Me)CMe=CH2]. Sulphenyl iodides may be important intermediates in reactions at disulphide bridges in peptides and proteins, and a report of the preparation of a stable sulphenyl iodide is notable. The observation that methanesulphenyl chloride dimerizes (in SO2 in the presence of a Lewis acid) to give MeSSMeCl Cl MeS=SMeCl Cl may be useful in explaining the course of certain electrophilic reactions of sulphenyl chlorides, and should stimulate a search for new reactions of aliphatic compounds of this series. 

ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTTiERS] (Vol 3) -esters of pSTERS, ORGANIC] (Vol 9)... 

Spectral Characteristics. The iafrared stretching frequency of the penicillin P-lactam carbonyl group normally occurs at relatively high frequencies (1770 1815 cm ) as compared to the absorptions for the secondary amide (1504-1695 cm ) and ester (1720-1780 cm ) carbonyl groups. 

The pharmacology of penicillins differs markedly from compound to compound but has been well reviewed (57). The majority of derivatives, including penicillin G and the antipseudomonal penicillins, ate unstable in gastric acid and ate not available orally. The isoxazolyl penicillins ate relatively acid stable but not consistendy well absorbed by the oral route. Nafcillin and oxacillin ate poody absorbed orally cloxacillin, dicloxacillin, and ducloxacillin ate more teUable. Penicillin V, ampicillin, and patticulady amoxicillin ate relatively well absorbed orally. Esters of ampicillin such as bacampicillin, pivampicillin, and talampicillin improve the level of oral absorption of ampicillin to that achieved by amoxicillin. Absorption can be diminished by food after oral adruinistration, however, and peak blood levels, usually achieved after 1 to 2 h, ate somewhat delayed after ingestion of food. 

Worldwide retail antibiotic sales in 1986 were approximately 11 biUion of which penicillins comprised approximately 2.5 biUion (66). Preparations containing ampicillin are estimated at 800 million whereas those containing amoxicillin are estimated at 1,020 million. Total sales include sales of ampicillin esters and the iireidopenicillins derived from ampicillin. Total sales of penicillins, including semisynthetic penicillins in the United States in 1987, were 25 million (67). Sales of amoxicillin, the largest single selling penicillin, were approximately 350 million. 

In an unusual application of the Wittig reaction, treatment of clavulanic acid derivatives and esters of penicillin V with methoxycarbonylmethylenetriphenylphosphorane afforded the corresponding exo-alkylideneazetidines. Thus penicillin V benzyl ester (104) gave (lOS) as a mixture of E and Z isomers. The /3-lactam could be regenerated by low-temperature ozonolysis (81CC929). 

The fragmentation patterns of relatively volatile derivatives of penicillins (e.g. benzyl-penicillin methyl ester) under electron impact (B-72MI51101) and chemical ionization (75MI51100) conditions have been described. For both techniques the primary fragmentation is that shown in Scheme 1. 

The following trivial names have been assigned to the penicillin transformation products shown (6), benzylpenicilloate (7), benzylpenaldic acid (8), D-penicillamine (9), a-methyl D-a-benzylpenicilloate (10), benzylpenillic acid (11), benzylpenillamine (12), benzyl-isopenillic acid (13), benzylpenilloic acid (14), benzylpenilloaldehyde (15), benzylpenicil-lenic acid (16) benzylpenillonic acid methyl ester and (17), dethiobenzylpenicillin methyl ester. 

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