Penicillin derivatives, reaction with

The sulfonium ylide derived chemistry of penicillins continues to meet the interest of several research groups. It is well known that intermolecular carbenoid attack at the sulfur atom generates a sulfonium ylide which undergoes spontaneous opening of the thiazolidine ring to furnish a l,2-sm>-penicillin 326). Novel examples of this reaction type were found upon Rb2(0Ac)4-catalyzed decomposition of diazomalonic esters in the presence of various penicillins this transformation constituted the opening step of a synthetic sequence directed towards 2-alkoxycarbonyl-cephems 345 a) or modified penicillins 345 b). Similar to its reaction with 4-thio-2-azetidinone... 

The earliest reports of constrained Ugi adducts derived from bi-functional precursors appeared in the 1960s with the preparation of penicillin derivatives such as 68, involving sequential Asinger and Ugi four-component reactions (Scheme 11.13). As such, the synthesis represents the shortest preparation of a known penicillin derivative [65], The /Mactam ring is formed after isocyanide addition to the cyclic Schiff base, followed by carboxylate nitrilium ion trapping and acyl transfer to give the final penicillin core. In this example, the amine and carboxylic acid inputs may be considered tethered. 

E5.3 Reaction of this penicillin-derived carbene, a, with thiophene, b, gives at least three adducts. The H NMR properties of two of the adducts, summarized below, are consistent with addition of the carbene to the thiophene double bond. Use die observed NOEs to elucidate the stereochemistry of these adducts. 

The ene-type chlorination, specific with this halogen atom, of alkenes would account for a somewhat different mode of halogen addition, giving useful allylic chlorides. Efficient and convenient reagents and methods developed are dichlorine monoxide (CI2O equation 36), r-butyl hypochlorite, and electrochemical reactions with chloride ion (equation 37). llie ene-type chlorination proceeds smoothly with 1,1-disubstituted alkenes (74) and (76) to give (75) and (77). Especially, dichlorine monoxide is a potential reagent for complex molecules such as penicillin and cephalosporin derivatives. ... 

Penicillins should be avoided in any patient who gives a history of a skin reaction or anaphylaxis to any penicillin derivative. To prevent mild skin reactions becoming severe when they occur, it is advisable to withdraw the culprit antibiotic not only when a type I reaction is suspected but in aU kinds of common rashes, in view of a possible epider-moljdic process. A diet free of dairy products was curative in 30 of 70 patients with positive tests (170). 

Morin et al. showed that the reaction of penicillin sulfoxides (162) with refluxing acetic anhydride leads to formation of the ring-expanded cepham derivatives (165) and compound (166 Scheme 41). Although this transformation was effected under Pummerer conditions, it occurs by a different mechanism, hence the term Abnormal Pummerer reaction . 

The halogen-magnesium exchange of a-halo carbonyl compounds has been reported to afford magnesium enolates which react with aldehydes to yield aldol products [107, 108]. The application of this reaction to the synthesis of penicillin derivatives has been reported (Scheme 3.94) [109-111]. 

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