Stereoselective enzyme-catalysed oxidation–reduction reactions of thioacetals–thioacetal sulphoxides by fungi

Abstract

Enzymes present in the fungus Mortierella isabellina catalyse the transfer of an oxygen atom to the cyclic thioaceta 1,3-dithian and from 1.3-dithian 1 -oxide, 1,3,5-trithian 1 -oxide, and cis-l,3-dithian 1,3-dioxide. The oxidation of 1,3-dithian and the acyclic thioacetal bis-(p-tolylthi0)methane to form the corresponding monosulphoxides occurred in the presence of growing cultures of Aspergillus foefidus and a Helminthosporium species. The degree and preferred direction of stereoselectivity occurring during the asymmetric oxidation and reduction steps was deduced from the enantiomeric excess (e.e.) and absolute stereochemistry of the isolated lf3-dithian 1 -oxide and p-tolylthio-(p-tolylsulphinyl) methane.THIOACETAL derivatives of carbonyl compounds serve as protecting groups and also as a method of rendering the carbonyl group susceptible to both electrophilic and nucleophilic attack (umpolung l), Current interest in the potential of optically active thioacetal monosulplioxide groups as chiral acyl anion equivalent^,^-^ allied to a paucity of information concerning the stability or fate of thioacetal groups during metabolism has prompted the present report. This study also forms part of a programme from these laboratories concerned with the mechanism and stereochemistry of enzyme-catalysed oxygen atom-transfer processes in xenobiotic metabolism (in animal: b a~t e r i a l ,~ and fungal systems). Thioether substrates have previously been transformed into sulphoxide 6-8 and sulphone products 63779 by fungi. While this microbial oxidation process is very common, the reverse (deoxygenation) step has rarely been observed.1°Three fungi which had previously been used to produce figurations of the isolated sulphoxide (2) were determined by comparison with the results recently obtained from the chemical resolution of (2). While the preferred conformation of (2) (chair form with the oxygen atom equatorial) is indicated in the formula it is established that this conformer is in a rapid state of equilibration with the alternative form having an axial oxygen atom (84% equatorial : 16?(, axial at equilibrium).ll The optical purities of the isolated metabolite (2) were relatively low ( <25y0) in comparison with alkyl-aryl thioether oxidations by these fungi6+' Thus a preference for the (+)-(R)-enantiomer [17-2270 enantiomeric TABLE 1Peracid a and enzyme-catalysed asyninietric oxidation of (1) and (3) Yield of Yield of t hioace tal monosulphoxide [a1 689 ( ") Optical Absolute yield ( Y o ) configuration recovered (yo) (%) (EtOH) Substrate Oxidant (1) 0,-iM. isabellina 29.34 16, 38 0, 0 0, 0 R F ( 3 ) 0 , -A . foetidus b 2 O c 0 R g (1) O,-Helminthospoviiim 8, 5 12,27 -35, -29 15,13 (1) 0 , -A . foetidus 32, 19, 42 40, 23, 52 +45, +51, +39 20, 22, 17 R (1) (+)-PCA h > 90 4-0.9 0.4 R (3) O,-HeZminthosporium b 3 -1 5 c 20 S (3) (+)-PCA b > 90 + 2 3 (3) 0 , -M . isabellina b b * (+)-Peroxycamphoric acid (PCA) in CHC1, solution a t -5 "C. No product could be detected. c In acetone solvent.optically pure sulphoxides from the corres...

Dioxygenase-catalysed oxidation of monosubstituted thiophenes: sulfoxidation versus dihydrodiol formation

“…The enzyme-catalysed mono-and dideoxygenation of disulfoxides has previously been reported in the fungus Mortierella isabellina. 27 A trace metabolite (0.1% yield) was identified as dihydrodiol 9A cis /9A trans ; its structure and stereochemistry are presented in section (d).…”

Donor substituted sulfonyl carbenes, 2: Organothio sulfonyl carbenes

“…73.5 °C of 2f was identical with that of the one-pot procedure, the m.p. 138.5 °C of 2g corresponded to the literature 42 16 : According to the described procedure starting from DMSO and acetic anhydride, in situ formed methylthiomethyl acetate was converted with sodium arenesulfinates 23a, 23b to afford 2a, 2b in larger amounts and in a high purity.…”

Rapid Delivery of Diazepam from Supersaturated Solutions Prepared Using Prodrug/Enzyme Mixtures: Toward Intranasal Treatment of Seizure Emergencies

“…These studies likely reflect a putative stereoselectivity of A.O. protease, a common property of enzymes (25)(26)(27).…”