Methyl penicillanate

Beside redox reactions, the S-l atom of penams can also be alkylated or chlorinated. On the one hand, by using Meerwein s salt or methyl fluorosulfonate, a series of methyl penicillanates have thus been S-methylated and their corresponding sulfonium salts 7 isolated and characterized (Figure 2) <1977TL71>. On the other hand, the use of sulfuryl chloride in carbon tetrachloride on the 6-unsubstituted methyl penicillanate led to the chlorosulfonium... 

P-Carbamoyloxy - methyl penicillanic acid sulfone derivatives... 

Substitution of the -methyl group of penicillanic acid sulfone has also been extensively investigated. The cyclopropyl sulfone (25, R = R = H,... 

Halogen atoms in the 6-position of penicillanic acid are readily removed under reducing conditions (Scheme 33). Methyl 6,6-dibromopenicillanate is converted first to the 6a-bromo... 

Chloro-6-fluorobenzaldoxime Methyl acetoacetate 6-Amino-penicillanic acid Sodium hydroxide... 

Common Name 6-(5-methyl-3-phenyl-2-isoxazoline-4-carboxamido)penicillanic acid, sodium salt 5-methy -3-phenyl-4-isoxazolylpenicillin, sodium salt... 

An internal alkylation via a nitrogen ylide has also been reported7. Thus, the bromide salt of methyl 6-[dimethyl(2-propenyl)ammonio]penicillanate gives a 75% yield of methyl 6/J-dimeth-ylamino-6oi-(2-propenyl)peniciHanate (see Table 2). 

Isonitriles 6, formed by dehydration of 6-(formylamino)penicillanates, can be alkylated by stabilized nucleophiles such as (bromomethyl)benzene and methyl 2-bromoacetate (see Table 2)8-9. In this case alkylation also takes place preferentially from the least hindered a-side of the enolate8,9. The corresponding cephalosporin isonitriles decompose on attempted alkylation8. 

SCHEME 6. Schering-Plough method for the preparation of methyl (6S, 1R, SR) 6-(l-trichloroethoxycarbonyloxyethyl) penicillanate (X). 

Azole approach. The /8-lactam ring in penicillanic acid derivatives can be expanded to a pyrimidine ring. Thus methyl 6/8-phthalimidopenicillanate (506) is transformed by CSI into the corresponding fused pyrimidine (507) with retention of the stereochemistry (78JCS(P1)817). Treatment of penicillanate S-oxides (508) with acyl isocyanates in a similar manner yields fused pyrimidines which subsequently eliminate water from the rearranged sulfoxide (74USP3850933). 

Penicillanate Methyl 6a-Allyl- -S,S-dioxid E21c, 2209 (Br - Allyl)... 

SEMI-SYNTHETIC yff-LACTAMASE INHIBITORS Clavulanic acid derivatives Penicillanic acid sulphone 6- -Halopenicillanic acid derivatives 6-Acetylmethylene penicillanic acid 6-Methoxymethylene penicillanic acid 6-Heterocyclylmethylene penam sulphones 2-y8-(Substituted methyl) penam sulphones 6-(Substituted methylene) penems... 

Methyl 6a-(2-Propenyl)penicillanate (Table 1) Typical Procedure3 ... 

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