School of Chemistry and Chemical Engineering, Queen's University Belfast, Belfast, UK.
Org Biomol Chem. 2012 Jan 28;10(4):782-90. doi: 10.1039/c1ob06678a. Epub 2011 Dec 1.
Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[b]thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[b]thiophene sulfoxide and 2-methyl benzo[b]thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b]thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca.: 25-27 kcal mol(-1). The absolute configurations of the benzo[b]thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring.
苯并[b]噻吩的不对称杂原子氧化反应可被存在于恶臭假单胞菌突变株和大肠杆菌重组全细胞中的甲苯双加氧酶（TDO）、萘双加氧酶（NDO）和苯乙烯单加氧酶（SMO）催化，生成相应的亚砜。TDO 催化氧化生成相对不稳定的苯并[b]噻吩亚砜；其二聚化，然后脱氢，导致分离出稳定的四环亚砜作为次要产物，顺式二氢二醇是主要代谢物。SMO 主要催化形成对映体富集的苯并[b]噻吩亚砜和 2-甲基苯并[b]噻吩亚砜，它们在环境温度下外消旋。使用 TDO 和 NDO 作为生物催化剂，对 2-和 3-甲基苯并[b]噻吩亚砜代谢物的三角硫翻转的能垒被发现约为：25-27 kcal mol(-1)。苯并[b]噻吩亚砜的绝对构型通过 ECD 光谱、X 射线晶体学和立体化学相关性确定。含有工程化形式的 NDO 的大肠杆菌突变株被发现改变了区域选择性，优先氧化噻吩环而不是苯环。
