Jan Verweij

Synthesis of Penicillin N and Isopenicillin N

Abstract Enantiomeric 2-(N-allyloxycarbonyl)aminoadipic acid 1-allyl esters were obtained from the corresponding 2-(N-trityl)aminoadipic acid diallyl esters following selective hydrolysis of the allyl 6-ester group and subsequent exchange of the trityl group by the allyloxycarbonyl function. The resulting monoacids were used to acylate 6-aminopenicillanic acid allyl ester using a carbodiimide-mediated coupling. The products, the l - and d -isomers of 6-[6-(2-(N-allyloxycarbonyl) aminoadipyl)]aminopenicillanic acid diallyl ester were deprotected in one step by catalytic allyl transfer using tetrakis-(triphenylphosphine)palladium(0), to afford isopenicillin N and penicillin N, respectively. The presented straightforward route to penicillin N and isopenicillin N is uniquely compatible with the sensitive nature of the condensation products and gives entry to a new and high yielding procedure that is superior to existing approaches.

Cephalosporanic acid 7β-alkylideneammonio salts

Abstract Reaction of 7β-aminocephalosporanic acid derivatives 2 with ketones under acidic conditions leads to the unprecedented formation of alkylideneammonio salts 4. 3′-Halogenated cephalosporanic acid derivatives bearing an unprotected carboxylgroup are normally considered to be sensitive intermediates that can easily undergo lactonization. However, these compounds are suprisingly stable when transformed into their 7β-alkylideneammonio salts and can thus be elegantly used as versatile intermediates in cephalosporin chemistry.