Penicillin oxides

β-Lactam Antibiotics: Structure-Activity Relationships

“…The design of chemical procedures to permit the synthesis of Sources: GUDDAL et al 1962;WOLFE 1976;HUFFMAN et al 1978;DE KONING et al 1977;CAMA et al 1974;HAMASHIMA et al 1978;BRYAN et al 1977;DOUGLAS et al 1978. many analogs of this type and to provide promise of commercial applicability is a remarkable chemical accomplishment.…”

Chemical Manipulations of the Penicillin Nucleus: A Review

“…Removal o f the sulphur atom from the thiazolidine ring is known to destroy the biological activity of penicillin (K aczka and Folkers, 1949); later work (Guddal, M orch and Tybring, 1962) has shown that the sulphur atom may be oxidised, to the sulphoxide and sulphone, without completely destroying the activity. Cavallito and Harley (1950) found that the sulphoxide o f penicillin is considerably more acid-stable than the unoxidized compounds.…”

“…Cavallito and Harley (1950) found that the sulphoxide o f penicillin is considerably more acid-stable than the unoxidized compounds. Methods of preparing penicillin sulphoxides have been given by Guddal et al (1962) Sheehan and Laubach (1951) discovered that penicillins sub stituted in the C5 locus (the so-called "bridgehead" carbon atom) were devoid o f activity. The 5-phenylpenicillins studied by these and other authors (see Bose and A njaneyulu, 1966) are important intermediates in the total synthesis of the penicillin molecule.…”

Recent chemistry of the β-lactam antibiotics

“…Such a transformation requires an oxidation of the methyl groups of penicillin and a ring expansion of the thiazolidine function. These stringent requirements were fulfilled as a result of a novel process originally described by Morin and coworkers.18 Oxidation of the penicillin ester 6 with sodium metaperiodate in aqueous dioxane,19 or other oxidants, [20][21][22] formed the sulfoxide 7. Treatment with acetic anhydride, under normal Pummerer conditions (a reaction used to convert sulfoxides bearing -hydrogen atoms to -acetoxy sul-fides23) left the sulfoxide 7 unaffected. In refluxing acetic anhydride, however, two major products (ratio 2:1) formed in 60% yield.…”

“…Methods for overcoming the directing influence of the secondary amide group in the 60 position have been developed. Since substitution at tervalent sulfur proceeds with inversion of configuration 33 it was argued that chlorination of the sulfur atom in the ester 22 (Scheme III) would give the chlorosulfonium ion 23 and that subsequent hydrolysis would produce the hitherto unknown (R)-sulfoxide 24. This scheme was realized SCHEME III OH' I by use of iodobenzene dichloride in aqueous pyridine,31•34 a reagent known to react by such a two-step mechanism. 35 Two alternative methods have also been invented.…”