Penicillin sulfoxide 6-methyl

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... 

Mata et al. also described a new and robust protocol for the solid-phase synthesis of 2(3-methyl substituted penam derivatives using Merrifield resin as support [210]. The work begins with immobilization of 6,6-dibromopenicillanic acid (171) onto Merrifield resin followed by oxidation with m-chloroperbenzoic acid (MCPBA) to obtain the resin-bound sulfoxide (173). The key-step involves the thermal rearrangement of the corresponding penicillin sulfoxide (Scheme 49). 

Rearrangement of a penicillin sulfoxide having the sulfonylurea side chain (230) produced a different spectrum of products (R. D. G. Cooper, 1970, unpublished results), namely, the thiazolinone (231) and the 2-methoxythiazoline (232). Presumably, these arose from intermediate 233 when, instead of the normal elimination of water to produce the thia-zoline, toluene sulfonamide was eliminated to yield 231. The 2-meth-oxythiazoline was then formed by methylation of 231 with trimethyl-phosphite. 

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. 

Section 5.10.3.2). Treatment of methyl 6-phthalimido penicillinate (jR)-sulfoxide (40) with JV-chlorosuccinimide in refluxing carbon tetrachloride gives an epimeric mixture of sulfinyl chlorides (41) which are ring closed to epimeric 3-methylenecepham sulfoxides (42a) using tin(IV) chloride. Reduction with phosphorus tribromide gives the desired methyl 7-phthalimido-3-methylenecepham 4-carboxylate (42b). 

It must be stressed, however, that the methyl alkyl sulfoxide rule is not valid for alkyl benzyl and alkyl allyl sulfoxides (222-224), where the electronic, steric, and solvent effects exert influences on the chiroptical phenomena in a way that is difficult to rationalize. This rule was found to be satisfactory and was used for the assignment of absolute configurations of steroidal (200,201,225), penicillin (226), and amino acid (227-230) sulfoxides. 

Winterfeldt has shown that the reaction of dimethyl sulfoxide with DMAD gives tetramethyl furantetracarboxylate (345), and it was suggested that this reaction may proceed through the intermediates 342, 343, and.344 (Scheme 52). The reaction of /-butylsulfenic acid with methyl propiolate, however, gives /3v -bis(/ra/is-carbomethoxy)divinyl sulfoxide (348) (Scheme 53). The penicillin S-oxide (349) is known to react with DMAD to give the adduct 352, and this reaction has been assumed to proceed through the sulfenic acid intermediate 350 (Scheme 54). ... 

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