Synthesis of tritium labelled mecillinam

Abstract

SummaryThe potent b-lactam antibiotic mecillinam has successfully been labelled with tritium. 2,3,4,7-Tetrahydro-1H-azepin-1-carbaldehyde was formed in a ring-closing metathesis reaction and then condensed with trimethylsilyl protected penicillanic acid to give dehydro-mecillinam. Pd/C catalysed tritiation then gave [ 3 H 2 ]-mecillinam (6-b (([3,4-3 H 2 ]hexahydro-1H-azepin-1-yl)methyleneamino)penicillanic acid) with a radiochemical purity of 96% and a specific activity of 24 Ci/mmol.

28 Radiochemistry

“…The simplest ways to produce tritium labelled molecules are by hydrogen/tritium exchange using either tritiated water, as in the preparation of L-tryptophan, 57 tritiumlabelled at the a-C position, or tritium gas, used to make labelled co-enzymes. 58 In the latter method a catalyst such as palladium-on-charcoal is sometimes helpful, as in the labelling 59 of the potent b-lactam antibiotic mecillinam. A more precise way of placing the tritium atoms in a molecule is to use tritium gas to reduce a double bond, here again a catalyst such as Pd/C is required.…”