Carter-Franklin Jayme N, Butler Alison
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106-9510, USA.
J Am Chem Soc. 2004 Nov 24;126(46):15060-6. doi: 10.1021/ja047925p.
Marine red algae (Rhodophyta) are a rich source of bioactive halogenated natural products. The biogenesis of the cyclic halogenated terpene marine natural products, in particular, has attracted sustained interest in part because terpenes are the biogenic precursors of many bioactive metabolites. The first enzymatic asymmetric bromination and cyclization of a terpene, producing marine natural products isolated from red algae, is reported. Vanadium bromoperoxidase (V-BrPO) isolated from marine red algae (species of Laurencia, Plocamium, Corallina) catalyzes the bromination of the sesquiterpene (E)-(+)-nerolidol producing alpha-, beta-, and gamma-snyderol and (+)-3beta-bromo-8-epicaparrapi oxide. alpha-Snyderol, beta-snyderol, and (+)-3beta-bromo-8-epicaparrapi oxide have been isolated from Laurencia obtusa, and each have also been isolated from other species of marine red algae. gamma-Snyderol is a proposed intermediate in other bicyclo natural products. Single diastereomers of beta-snyderol, gamma-snyderol, and mixed diastereomers of (+)-3beta-bromo-8-epicaparrapi oxide (de = 20-25%) are produced in the enzyme reaction, whereas two diastereomers of these compounds are formed in the synthesis with 2,4,4,6-tetrabromocyclohexa-2,5-dienone (TBCO). V-BrPO likely functions by catalyzing the two-electron oxidation of bromide ion by hydrogen peroxide producing a bromonium ion or equivalent in the active site that brominates one face of the terminal olefin of nerolidol. These results establish V-BrPO's role in the biosynthesis of brominated cyclic sesquiterpene structures from marine red algae for the first time.
海洋红藻（红藻门）是生物活性卤化天然产物的丰富来源。特别是环状卤化萜类海洋天然产物的生物合成，一直备受关注，部分原因是萜类是许多生物活性代谢物的生物前体。本文报道了从红藻中分离得到的萜类化合物的首次酶促不对称溴化和环化反应，该反应生成了从红藻中分离得到的海洋天然产物。从海洋红藻（劳伦藻属、团扇藻属、珊瑚藻属）中分离得到的钒溴过氧化物酶（V-BrPO）催化倍半萜（E）-（+）-橙花叔醇的溴化反应，生成α-、β-和γ-斯奈德醇以及（+）-3β-溴-8-表卡帕拉皮氧化物。α-斯奈德醇、β-斯奈德醇和（+）-3β-溴-8-表卡帕拉皮氧化物已从钝形劳伦藻中分离得到，并且也从其他海洋红藻物种中分离得到。γ-斯奈德醇是其他双环天然产物中的一种推测中间体。在酶促反应中生成了β-斯奈德醇、γ-斯奈德醇的单一非对映异构体以及（+）-3β-溴-8-表卡帕拉皮氧化物的混合非对映异构体（de = 20-25%），而在与2,4,4,6-四溴环己-2,5-二烯酮（TBCO）的合成反应中形成了这些化合物的两种非对映异构体。V-BrPO可能通过催化过氧化氢对溴离子的双电子氧化反应，在活性位点生成溴鎓离子或其等价物，从而对橙花叔醇末端烯烃的一面进行溴化反应。这些结果首次确定了V-BrPO在海洋红藻溴化环状倍半萜结构生物合成中的作用。
