The preparation of a number of penicillins with 2-biphenylyl side chains is described. Some of the substituted 2-biphenylcarboxylic acids used as intermediates were synthesized for the first time or were prepared by new methods. These penicillins were active against penicillin G-resistant as well as penicillin G-susceptible staphylococci.The penicillin nucleus, 6-aminopenicillanic acid, which became available in quantity as a biosynthetic product in 1959,1 has been used as the starting material for the chemical preparation of a great number of "semisynthetic" penicillins.2 Previously, total biosynthesis had been the only commercially feasible method for making penicillins, and, out of the limited number so obtainable, only two, penicillins G and V (benzylpenicillin and phenoxymethylpenicillin, respectively), had found wide clinical use. These two antibiotics are active against many Gram-positive organisms, including "susceptible" staphylococci, but they are not effective against the increasing number of "resistant" strains of staphylococci which are being encountered clinically. In this paper the term "susceptible" is used for those staphylococci which are sensitive to penicillins G and V, and "resistant" for those which are unaffected by high levels (e.g. 500-1000 /ml.) of these antibiotics because they have the ability to produce a lactam-opening penicillinase.3The object of the work described in this and the following papers was to find a penicillin with good activity against both susceptible and resistant staphylococci as defined above. An early semisynthetic product, methicillin4 (2,6-dimethoxyphenylpenicillin), has approximately equal activity against these two classes of organism because it is stable to staphylococcal penicillinase.5 However, this activity is low, pre-(1) F.

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2‐Aminobenzimidazole reacts with α,β‐unsaturated carboxylic acid chlorides or esters to give only pyrimido [1,2‐a] benzimidazol‐2‐(1H) ones. β‐Ethoxymethylenemalonie acid derivatives or β‐ketocarboxylic acid derivatives give only pyrimido [1,2‐a] benzimidazol‐4‐(1H)ones. Structural assignments based on nmr and chemical manipulations are discussed.

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