磺胺类和氨基磺酸类活性天然产物氮硫键生物合成研究进展

Research progress of nitrogen-sulfur bond biosynthesis in naturally occurring bioactive sulfonamides and sulfamates

磺胺类和氨基磺酸类天然产物是指生物体产生的含氮(-3价)硫(+6价)键的化合物,化学通式可以分别表示为RSO_(2)NR’R’’和ROSO_(2)NR’R’’。磺胺和氨基磺酸基团的化学结构和电子云密度分布与磷酸基团相似,在生物体内可能占据受体蛋白质(例如碳酸酐酶、环氧化酶-2和乙酰胆碱酯酶等)的活性位点,从而影响其生理功能。磺胺类和氨基磺酸类天然产物表现出各种各样的生物活性,包括抗菌、抗病毒、抗炎症、抗肿瘤和抗凝血等。目前磺胺类和氨基磺酸类天然产物的氮硫键形成的反应有4种类型,分别是:(1)磺酸基转移酶催化的磺酸基团转移反应;(2)氨基转移酶催化的氨基转移反应;(3)SbzM催化的氧化反应;(4)XiaH介导的自由基共聚合反应。本文将对这4种氮硫键形成机制进行综述。

Sulfonamide and sulfamate natural products are naturally occurring compounds containing nitrogen(-Ⅲ)-sulfur(+Ⅵ) bonds(N-S bonds), of which the chemical formulas can be expressed as RSO2NR’R’’ and ROSO2NR’R’’, respectively. Sulfonamide and sulfamate groups share similar structures and density distribution of electronic cloud with that of the phosphate group, so that they can occupy the active sites in some receptor proteins(such as carbonic anhydrase, cyclooxygenase-2, and acetylcholinesterase), and thus have an effect on their physiological function. Sulfonamide and sulfamate natural products show a wide range of biological activities, including antibacterium, antivirus, anti-inflammatory, antitumor, anticoagulation, and so on. Until now, four N-S bond biosynthetic pathways of naturally occurring sulfonamides and sulfamates have been characterized, including(1) sulfonic group transfer reactions catalyzed by sulfotransferases;(2) amino group transfer reactions catalyzed by aminotransferases;(3) oxidation reaction catalyzed by SbzM;(4) radical copolymerization catalyzed by XiaH. In this review, these four nitrogen-sulfur bond formation mechanisms will be summarized.