Efficient Synthesis of (S)‑1-Boc-3-aminopiperidine
in a Continuous Flow System Using ω‑Transaminase-Immobilized
Amino-Ethylenediamine-Modified Epoxide Supports
posted on 2022-04-15, 17:10authored byXiangxiang Wang, Youyu Xie, Zhicai Wang, Ke Zhang, Hualei Wang, Dongzhi Wei
We
developed a continuous flow system using ω-transaminase
covalently immobilized on an epoxy resin modified with ethylenediamine
(EDA) to synthesize (S)-1-Boc-3-aminopiperidine,
which is a key intermediate for several novel inhibitors. A second
functional group (−NH3+) was introduced
to rapidly adsorb ω-transaminase, which was further rigidified
by multipoint covalent attachment to the modified resin with high
binding efficiency (>95%) and activity recovery (75%). The resulting
immobilized ω-transaminase was stable with 90% residual activity
after 15 reuse cycles. We synthesized (S)-1-Boc-3-aminopiperidine
using this continuous flow system, and 95% conversion was obtained
within 10 min of residence. The system was continuously operated for
24 h and achieved a space–time yield of 930.73 g·L–1·day–1, indicating outstanding
reaction efficiency. This efficient continuous bioprocess has potential
for large-scale production of (S)-1-Boc-3-aminopiperidine.