114763-28-9

Upstream product

• 100-42-5 styrene 
• 108-86-1 bromobenzene 
• 591-50-4 iodobenzene 
• 7486-35-3 tri-n-butyl(vinyl)tin 
• 67451-62-1 cis-(1S,2S)-1,2-dihydroxy-3-bromocyclohexa-3,5-diene 

Relevant academic research and scientific papers

Site-Directed Mutagenesis Studies on the Toluene Dioxygenase Enzymatic System: Role of Phenylalanine 366, Threonine 365 and Isoleucine 324 in the Chemo-, Regio-, and Stereoselectivity

Toluene Dioxygenase (TDO) enzymatic complex has been widely used as a biocatalyst for the regio- and enantioselective preparation of cis-cyclohexadienediols, which are very important starting materials for organic synthesis. However, the lack of regio- and stereodiversity of the dioxygenation process by TDO and related dioxygenases constitutes a clear drawback when planning the use of these diols in synthetic schemes. In this work, we developed three TDO mutants in residues phenylalanine 366, threonine 365 and isoleucine 324, with the aim to alter the chemo-, regio- and stereoselectivity of the biotransformation of arenes. While no changes in the regioselectivity of the process were observed, dramatic variations in the chemo- and enantioselectivity were found for mutants I324F, T365N and F366 V in a substrate-dependent manner. (Figure presented.).

Biocatalytic asymmetric dihydroxylation of conjugated mono-and poly-alkenes to yield enantiopure cyclic cis-diols

Dioxygenase-catalysed asymmetric dihydroxylation, of a series of conjugated monoalkenes and polyenes, was found to yield the corresponding monols and 1,2-dihydrodiols. The diol metabolites were obtained from monosubstituted, gem-disubstituted, cis-disubstituted, and trisubstituted alkene substrates, using whole cells of Pseudomonas putida strains containing toluene and naphthalene dioxygenases. Dioxygenase selection and alkene type were established as important factors, in the preference for dioxygenase-catalysed 1,2-dihydroxylation of conjugated alkene or arene groups, and monohydroxylation at benzylic or allylic centres. Competition from allylic hydroxylation of methyl groups was observed only when naphthalene dioxygenase was used as biocatalyst. The structures, enantiomeric excess values and absolute configurations of the bioproducts, were determined by a combination of stereochemical correlation, spectroscopy (NMR and CD) and X-ray diffraction methods. cis-1,2-Diol metabolites from arenes, cyclic alkenes and dienes were generally observed to be enantiopure (> 98% ee), while 1,2-diols from acyclic alkenes had lower enantiomeric excess values (2-symmetrical ketone.

Medium-scale preparation of useful metabolites of aromatic compounds via whole-cell fermentation with recombinant organisms

The whole-cell fermentation of aromatic coumpounds with Escherichia coli JM109 (pDTG601) on a medium scale (10-15L) produces enantiopure cyclohexadienediols. A detailed procedure for the fermentation is described, and yields for several metabolites are provided. A similar procedure using E. coli JM109 (pDTG602) affords catechols. The dienediols are useful for asymmetric synthesis, and several important targets originating from these metabolites are tabulated.

Enzymatic and chemoenzymatic synthesis and stereochemical assignment of cis-dihydrodiol derivatives of monosubstituted benzenes

Toluene dioxygenase-catalysed oxidation of mono-substituted benzene substrates (R = F, Cl, Br, I, Me, Et, CH2OAc, CH=CH2, C=CH, CF3, CN, OMe, OEt, SMe) in growing cultures of Pseudomonas putida UV4 yielded the corresponding cis-dihydrodiol metabolites. Palladium-catalysed cross-coupling of cis-(1S,2S)-1,2-dihydroxy-3-iodocyclohexa-3,5-diene with a range of tributyltin compounds provided a chemoenzymatic route to a further series of cis-dihydrodiol derivatives of monosubstituted benzenes (R = D, CH2CH=CH2, Bun, SEt, SPr1, SBu1, SPh, SC6H4Me-4). The enantiopurities and absolute configurations of the cis-dihydrodiols, obtained by both enzymatic and chemoenzymatic routes, were determined by several new methods including 1H NMR spectroscopic analysis of the bis-MTPA esters of the 4-phenyl-1,2,4-triazoline-3,5-dione cycloadducts, X-ray crystallography, circular dichroism spectroscopy and stereochemical correlation.

New Diol Metabolites Derived by Biooxidation of Chlorostyrenes with Pseudomonas putida: Determination of Absolute Stereochemistry and Enantiomeric Excess by Convergent Syntheses

The three isomers of chlorostyrenes were subjected to whole cell biooxidation by means of a mutant strain of Pseudomonas putida 39D.The metabolites were isolated and their absolute stereochemistry determined by conversion to known standards derived from 1-ethenyl-2,3-dihydroxycyclohexa-4,6-diene whose absolute configuration has been previously established.The extent of ring vs side chain oxidation of the chlorostyrene isomers was evaluated and the enantiomeric excess determined for all compounds.

Enzymatic and Chemical Syntheses of cis-Dihydrodiol Derivatives of Monocyclic Arenes

Metabolism of bromobenzene and iodobenzene by growing cultures of Pseudomonas putida UV4 gave the corresponding cis-dihydrodiol products 1 and 2 in high yields; subsequent direct chemical substitution of the halogen atoms in these metabolites provided a new range of enantiomerically pure cis-dihydrodiols of known absolute configuration.