Polymerization of N-carboxy anhydrides (NCAs) is the primary process used to prepare polypeptides. The synthesis of various pure NCAs is key to the efficient synthesis of polypeptides. The only practical method that can be used to synthesize NCAs requires harsh acidic conditions that make acid-labile substrates unusable and results in an undesired ring opening of NCAs. Basic-to-acidic flash switching and subsequent flash dilution technology in a microflow reactor was used to demonstrate the synthesis of NCAs. It is both rapid (0.1 s) and mild (20 °C) and includes substrates containing acid-labile functional groups. The basic-to-acidic flash switching enabled both an acceleration of the desired NCA formation and avoided the undesired ring opening of NCAs. The flash dilution precluded the undesired decomposition of acid-labile functional groups. The developed process allowed the synthesis of various NCAs which cannot be readily synthesized using conventional batch methods.
Peptide drugs have garnered much attention in recent years. However, conventional peptides ynthesis requires an excessa mount of expensive reagents of low atom economy,a nd the large amount of waste produced by these reagents complicates the purification of desired peptides. Solid-phase approaches simplify the purification of these peptides, but these requiree xpensive solid-phase, excess amounts of reagents,s ubstrates, and solvents. This makes it important to develop high-yielding, cost-effective, andl ess wasteful synthetic approaches. Micro-flow technology (reac-tion space 1mm) has produced manya dvantages over conventional batch synthesis. Thea dvantages include precise control of short reactiont ime and temperature, high levels of light penetration efficiency,l oweredr isks of handling dangerous compounds, and ready scale-up withh igh reproducibility.M icro-flow peptides yntheses using these advantages have been reported in recent years. This review summarizes the solid-phase and solution-phases yntheses of a-a nd b-peptides and of cyclic peptidesu sing micro-flow technology.[a] Dr.
Bayesian optimization (BO) is regarded as an efficient approach that can identify optimal conditions using a restricted number of experiments. Despite demonstrated potential of BO, applications of BO‐based approaches in synthetic organic chemistry remain limited. Herein, we achieved the first rapid and mild (5.1 s, 20 °C) one‐flow synthesis of unsymmetrical sulfamides from inexpensive sulfuryl chloride. Undesired reactions were successfully suppressed and the risk in handling sulfuryl chloride was minimized by the use of micro‐flow technology. The reaction conditions producing ≥75 % yield were identified by a machine learning approach based on BO. It was demonstrated that BO produced the desired reaction conditions with a small number of experiments (19 and 10 experiments) in the entire search space (10,500 combinations of reaction conditions). Gaussian process (GP) models produced by BO provided the relationships between combinations of reaction parameters and outputs (RCRPO).
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