Lomustine is a widely used class of highly lipophilic alkylated anticancer drugs that produce chloroethyl carbon ions and carbamides

in the body. These electrophilic compounds attack the nucleophilic sites on DNA, forming alkylated products and exerting pharmacological

effects. Other categories of anticancer drugs, such as streptomycin, bleomycin, and anthracyclines, require biological activation to react with

cellular targets, while lomustine does not require pre activation. Unlike the N7 alkylating reagent that acts on guanine, lomustine forms a chloroethylated

adduct in O6, leading to cross-linking of DNA between strands. If DNA is not repaired, this cross-linking will cause double strand breakage during DNA

replication, leading to apoptosis and cell death. Lomostine, as an oral anti-tumor drug, should be taken every 6 weeks.

The David H. Thompson research group of Purdue University recently reported a new process of continuous flow synthesis of lomustine,

and used desorption electrospray ionization mass spectrometry (DESI-MS) to analyze and detect it to guide the optimization of the process.

The final process route involves two reactions connected in series, without separating intermediates. It has the characteristics of simple reactor

equipment and cheap raw materials, which can reduce production costs (the reaction process is shown in Figure 1). The relevant results were

published in the journal Org. Process Res. Dev.2019, 23, 3334-341 (DOI: 10.1021/acs. oprd. 8b00387).

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