Stereoselective Transaminase-Mediated Synthesis of Serotonin and Melatonin Receptor Agonists
Stereoselective Transaminase-Mediated Synthesis of Serotonin and Melatonin Receptor Agonists
复制标题
立体选择性转氨酶介导的血清素和褪黑激素受体激动剂的合成
DOI：
10.1002/adsc.202200146
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发表时间：
2022
影响因子：
5.4
通讯作者：
Baud D
中科院分区：
文献类型：
--
作者：
Baud D
转氨酶在药物或药物前体的立体选择性合成中具有重要的潜力。在这里，从一种前手性β-四氢萘酮开始，已经开发了四种5-羟色胺/褪黑激素受体激动剂的短而有效的化学酶促合成。关键步骤是立体选择性转胺的前手性酮，以高产率和对映体过量产生两种对映体的8-甲氧基-2-氨基四氢萘。随后进行酰胺化，得到8-甲氧基-2-乙酰亚胺基四氢化萘，或通过几个简单的化学步骤得到8-羟基-2-氨基二丙基四氢化萘。
Transaminase enzymes have significant potential for the stereoselective synthesis of drugs or drug precursors. Here, starting from one prochiral β‐tetralone, a short and efficient chemoenzymatic synthesis of four agonists of the serotonin/melatonin receptors have been developed. The key step is the stereoselective transamination of the prochiral ketone to produce both enantiomers of 8‐methoxy‐2‐aminotetraline in high yields and enantiomeric excesses. This was followed by either amidation to give the 8‐methoxy‐2‐acetimidotetralines or several facile chemical steps to the 8‐hydroxy‐2‐aminodipropyltetralines.