Penicillin sulfoxide methyl ester

Treatment of 107 and 108 with triethylamine resulted in the cyclized product (113). Use of the penicillin sulfoxide methyl ester (114) gave the same mixture of sulfoxide epimers which could then be separated (115 and 116). Base treatment of the separated isomers showed that 115 cy-... 

Barton et a/.618-818 have shown that the sulfenic intermediates produced thermally from penicillin sulfoxides can be added across acetylenic esters to produce conjugated sulfoxides in good yields. For example, the methyl ester 95 with DMAD afforded the isomeric... 

To determine which carbon atom of the isopropenyl functionality in the azetidinone sulfinyl chloride participates in the ring closure, the above sequence of steps was repeated starting with the penicillin sulfoxide ester deuterated at the C-2 methyl position. The stereochemistry of this compound (70) had been previously established (Cooper, 1970). The NMR spectrum of the final product, methyl phthalimido-2-dideutero-3-methy-lenecepham-4-carboxylate (71), showed clearly a selective incorporation of deuterium at the C-2 position. It was, therefore, concluded that the olefinic carbon in the intermediary sulfinyl chloride was involved in the S—C-2 bond formation. 

The Hatfield protocol was used for the synthesis of 6p-acylamino-2-methylpenems, where a natural penicillin is the substrate and acetic anhydride is the reagent isobutyric anhydride was also employed with success [48]. In particular, esters of penicillin V sulfoxide and its 6a-methoxy and 6a-methyl derivatives 138a c were converted to the corresponding azetidinyl-4-thio-esters of formula 137, isomerized to the conjugated AT-butenoates of general formula 127, and thence oxidatively cleaved to 1 if-4-thioesters 139a c [48, 87, 88] without problems, apart from the competing formation of thiazoline-azetidin-ones 140. 

The metamorphosis of penicillin V sulfoxide ester (XIII) into a de-acetoxy cephalosporin (XIV) has been reported in detail by Morin and co-workers. The introduction of the acetoxy function into the 3-methyl group of XIV generating a cephalosporanic acid (XV) has now been accomplished . ... 

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