High-Performance Pd/AC Catalyst for Meropenem Synthesis Based on Selective Surface Modification of Activated Carbon

Pd/N, S co-doped activated carbon as a highly-efficient catalyst for the one-pot synthesis of meropenem

“…The possible deprotection mechanism of meropenem synthesis is shown in Scheme 2. According to reported results, 32,60–63 the deprotection mechanism proceeds via the dissociation of H 2 and protected meropenem, which were later adsorbed onto a Pd/C catalyst at the active sites, accompanied by C–O bond activation. Thereafter, p -nitrobenzyloxycarbonyl and p -nitrobenzyl (PNB) were subject to hydrogenation to form –C–COOH and –N–COOH, eliminating PNB.…”

“…The meropenem synthesis method adopted for this study was based on the step-by-step synthesis method 32 established according to the characteristics of the reaction system of the industrial one-pot synthesis of meropenem. 9,10 Firstly, protected meropenem 4 (15 g) and tetrahydrofuran (200 mL, THF) were mixed and then placed in a steel autoclave (1000 mL).…”

“…N-doped/N, S co-doped AC preparation Based on the synthesis method 32 and the desired sulfur contents of 0 wt%, 1 wt%, 2 wt%, 3 wt%, and 4 wt%, 12 g urea, together with 0 g, 0.712 g, 1.424 g, 2.137 g, or 2.849 g thiourea, was added into distilled water (150 mL), followed by the addition of 30 g AC (CG1P, Norit). The resulting mixed solution was then stirred for 20 h at 25 °C, filtered, and dried for 4 h at 120 °C.…”

“…Our experience of finding it difficult to filter the Pd/C catalyst for the step-by-step synthesis of meropenem out of the hydrogenation reaction solution led us to believe that crude meropenem crystals could not be separated in the one-pot synthesis. 32 In addition, unlike in the step-by-step synthesis, the protected meropenem in the one-pot synthesis is not well-purified and may contain poisoning impurities, such as excess side chain 3, which contains a sulfur-containing species, thiol, causing significant metal catalyst deactivation. Considering this, we deduced that the amount of side chain 3 would affect the Pd/ C catalyst's catalytic performance.…”

“…31 More recently, we have reported a Pd-supported N-doped AC catalyst (5% Pd/C) that offered a greater meropenem yield and lower impurity levels during the step-by-step synthesis of meropenem. 32 Therefore, considering the studies discussed above and building on our previous research, a significant study on Pd-supported N, S co-doped AC catalysts in the one-pot meropenem preparation is necessary.…”