Mother nature's gifts to diseases of man OH cne16明R In order to give extra 'medicinal life'to B-lactams that were no longer resistant to the common B-lactamases.in the late 1960s and earlv 1970s efforts were made,particularly by Beecham(now part of GlaxoSmithKline) and Pfizer to find molecules that would have similar pharmacokinetics to the B-lactams but would inhibit the 'regular'B-lactamases that were part of the pathogenic microbe's defense systems.Beecham discovered the clavulanate family with clavulanic acid(9)being incorporated into the combination known as Augmentin a 1:1 mixture of amoxicillin and clavulanic acid(9)launched in 1981,thus extending the franchise of this particular B-lactam well beyond its original patent date. Along with the search for the B-lactamase inhibitors,efforts were under- way to produce the simplest B-lactam,the monobactam.Following many years of unsuccessful research at major pharmaceutical houses,predomi- nately in the synthetic areas,came the reports from Imada et al.in 1981 [18] and a Squibb group led by Sykes [19],who both demonstrated the same basic monobactam nucleus(10).What is important to realize is that no molecules synthesized before the discoveries of these NPs had a sulfonvl group attached to the lactam nitrogen,which is an excellent method for stabilizing the sin- gle ring.Since that time a significant number of variations upon that theme have been placed into clinical trials and in some cases,into commerce 7Mother nature’s gifts to diseases of man 7 In order to give extra ‘medicinal life’ to `-lactams that were no longer resistant to the common `-lactamases, in the late 1960s and early 1970s, efforts were made, particularly by Beecham (now part of GlaxoSmithKline) and Pfizer to find molecules that would have similar pharmacokinetics to the `-lactams but would inhibit the ‘regular’ `-lactamases that were part of the pathogenic microbe’s defense systems. Beecham discovered the clavulanate family with clavulanic acid (9) being incorporated into the combination known as Augmentin® a 1:1 mixture of amoxicillin and clavulanic acid (9) launched in 1981, thus extending the franchise of this particular `-lactam well beyond its original patent date. Along with the search for the `-lactamase inhibitors, efforts were under￾way to produce the simplest `-lactam, the monobactam. Following many years of unsuccessful research at major pharmaceutical houses, predomi￾nately in the synthetic areas, came the reports from Imada et al. in 1981 [18] and a Squibb group led by Sykes [19], who both demonstrated the same basic monobactam nucleus (10). What is important to realize is that no molecules synthesized before the discoveries of these NPs had a sulfonyl group attached to the lactam nitrogen, which is an excellent method for stabilizing the sin￾gle ring. Since that time a significant number of variations upon that theme have been placed into clinical trials and in some cases, into commerce