Enzymatic oxidation of thioanisoles: isolation and absolute configuration of metabolites

Dioxygenase-catalysed oxidation of alkylaryl sulfides: sulfoxidation versus cis-dihydrodiol formation

“…Biotransformations of the para-substituted- (8,10,12) and ortho-substituted-methyl phenyl sulfides (23)(24)(25)(26) yielded the corresponding cis-dihydrodiols (18)(19)(20)(31)(32)(33)(34) using P. putida UV4 (Schemes 4, 5 and Table 2) in addition to the corresponding sulfoxides (13-15, 17, 27-30, Table 2). The isolated yields of cis-dihydrodiols 18-20, 31-34 were generally low (1-24%), employing the standard extraction procedure.…”

“…cis-Dihydrodiol 20 has however recently been isolated from sulfide 10 in good yield (2.3 g L −1 ) by Hudlicky et al using the recombinant strain E. coli JM109(pDTG601). 33 Metabolites 18-20, in common with the unstable cis-dihydrodiol 7, 25,33 contain the electron-donating SMe group which has been found to facilitate spontaneous dehydration to yield the corresponding phenolic products. 34 The result of our first biotransformation run, using methyl para-tolyl sulfide 12 with P. putida UV4, was exceptional; it gave a higher yield (20%) of the corresponding cis-dihydrodiol sulfide 22 relative to the sulfoxide 17 (3%, Scheme 3).…”

“…In this article, the focus is on the dioxygenase-catalysed biotransformation of a range of methyl para- (8)(9)(10)(11)(12) and orthosubstituted phenyl sulfides (23)(24)(25)(26), where both the corresponding cis-dihydrodiol sulfide (18-20, 22, 31-34) and sulfoxide metabolites (13)(14)(15)(16)(17)(27)(28)(29)(30) were isolated. The ee values and absolute configurations of cis-dihydrodiols (18)(19)(20)22,(31)(32)(33)(34) were determined by a combination of chemoenzymatic synthesis, formation of chiral boronate derivatives prior to 1 H-NMR analysis, and circular dichroism (CD) spectroscopy. This study also provides an opportunity to evaluate the relative stereodirecting effect of the SMe group in comparison with other atoms and groups, in the context of TDO biocatalysis of cis-dihydroxylation of disubstituted benzene substrates.…”

Benefits of Unconventional Methods in the Total Synthesis of Natural Products

“…45 A highly selective reduction of vinyl iodide over vinyl bromide in 81 was also achieved, as was oxidation of the diene diol 82 to the syn epoxide 84 (via the intermediate bromohydrin 83 ). 45 Electrochemical reduction of the alkenyl bromide 85 derived chemoenzymatically from p -bromothioanisole was accomplished selectively using a mercury pool cathode to furnish diene diol 86 , 46 as shown in Figure 10. Such selectivity might not be attainable by using conventional reducing agents.…”

“…It should be noted that diol 86 was not available by enzymatic dihydroxylation of thioanisole (only the corresponding sulfoxide was obtained). 46…”