67451-62-1

Upstream product

• 108-86-1 bromobenzene 

Downstream Products

• 140210-12-4 (1S,2R)-3-Phenylethynyl-cyclohexa-3,5-diene-1,2-diol 
• 140210-13-5 (1S,2R)-3-Hex-1-ynyl-cyclohexa-3,5-diene-1,2-diol 
• 154097-67-3 (1S,2S,3S,4S)-5-bromo-5-cyclohexene-1,2,3,4-tetraol 
• 154013-20-4 (1R,2R,3S,4S)-5-bromo-5-cyclohexene-1,2,3,4-tetraol 
• 174817-06-2 cis-(1S,2S)-1,2-dihydroxy-3-bromocyclohex-3-ene 
• 380621-87-4 (2S,3aS,7aS)-4-bromo-3a,7a-dihydro-2-phenyl-1,3-benzodioxole 
• 172483-26-0 N-((3aS,4R,5R,7aR)-2,2-Dimethyl-3a,4,5,7a-tetrahydro-[5,5']bi[benzo[1,3]dioxolyl]-4-yl)-4-methyl-benzenesulfonamide 
• 393165-27-0 (1R,2R,3S,4S,5S,6R)-4,5-(isopropylidenedioxy)-3-[(tert-butyldimethylsilyl)oxy]-6-N-(3',4'-methylenedioxybenzyl)-N-(4'-methylphenylsulfonyl)-7-oxabicyclo[4.1.0]heptane 
• 393165-23-6 (1S,2R,3R,4R,5S,6S)-3,4-(isopropylidenedioxy)-5,6-dihydroxy-7-(4'-methylphenylsulfonyl)-7-azabicyclo[4.1.0]heptane 
• 393165-24-7 (1S,2R,3R,4S,5R,6S)-3,4-(isopropylidenedioxy)-5,6-O-sulfuryl-7-(4'-methylphenylsulfonyl)-7-azabicyclo[4.1.0]heptane 
• 393165-25-8 (1S,2R,3R,4S,5S,6S)-3,4-(isopropylidenedioxy)-5-hydroxy-6-benzoyl-7-(4'-methylphenylsulfonyl)-7-azabicyclo[4.1.0]heptane 
• 393165-26-9 (1S,2R,3R,4S,5S,6S)-3,4-(isopropylidenedioxy)-5-[(tert-butyldimethylsilyl)oxy]-6-hydroxy-7-(4'-methylphenylsulfonyl)-7-azabicyclo[4.1.0]heptane 
• 460731-73-1 N-[(1R,2R,3S,4S,5S,6S)-2-(1,3-benzodioxol-5-yl)-3,4-dihydroxy-5,6-(isopropylidenedioxy)cyclohex-1-yl]-4-methylbenzenesulfonamide 
• 460731-72-0 (1S,2R,3R,4S,5S,6S)-3,4-(isopropylidenedioxy)-5-[(tert-butyldimethylsilyl)oxy]-6-benzoyl-7-(4'-methylphenylsulfonyl)-7-azabicyclo[4.1.0]heptane 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 10-benzyloxy-Narciclasine

A chemoenzymatic convergent synthesis of 10-benzyloxy narciclasine from bromobenzene was accomplished in 16 steps. The key transformations included toluene dioxygenase-mediated hydroxylation, nitroso Diels-Alder reaction and intramolecular Heck cyclization. The unnatural derivative of narciclasine was subjected to biological evaluation and its activity was compared to other C-10 and C-7 compounds prepared previously.

Chemoenzymatic synthesis of hygromycin aminocyclitol moiety and its C2 epimer

This manuscript describes the enantioselective synthesis of the aminocyclitol moiety of the antibiotic hygromycin A in eight steps and 39 % overall yield from a non-chiral starting material. The sequence made use of an initial enzymatic step to transfer chirality to an aromatic ring and was followed by selective organic chemistry transformations (oxidation, pro-tection, azidation, hydrolysis) of the six-membered ring in order to achieve the target. The approach is also amenable to the synthesis of other related unnatural analogues as exemplified by the synthesis of the C2 epimer of the natural aminocyclitol. All the intermediates were fully characterized, and the absolute stereochemistry assigned by spectrometric methods.

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.).

A chemoenzymatic route to chiral siloxanes

An approach employing two enzymes—toluene dioxygenase and immobilized lipase B from Candida antarctica (N435)—was explored as a potential biocatalytic method for the coupling of chiral diols with siloxane species. Analysis of reaction mixtures using1H NMR spectroscopy suggested that up to 66% consumption of the siloxane starting materials had occurred. Oligomeric species were observed and chiral products from the coupling of a cyclic diol with a siloxane molecule were isolated and characterized by MALDI-ToF MS and GPC. Immobilized lipases from Rhizomucor miehei and Thermomyces lanuginosus were also explored as potential catalysts for the coupling reactions, however, their use only returned starting material.

Aza and oxo Diels-Alder reactions using cis-cyclohexadienediols of microbial origin: Chemoenzymatic preparation of synthetically valuable heterocyclic scaffolds

Aza and oxo Diels-Alder reactions using enantiopure cis-cyclohexadienediols were studied. These dienediols were obtained from the biotransformation of monosubstituted arenes using bacterial dioxygenases (toluene and benzoate dioxygenases). Ethyl glyoxylate and its N-tosyl imine were used as dienophiles to afford the corresponding hetero Diels-Alder bicyclic adducts with excellent regio- and stereoselectivities. Quantum chemical calculations at the B3LYP/6-31+G(d,p) level of theory were performed to rationalize the observed selectivities especially the stereochemical aspects of the cycloadditions. The synthetic importance of these adducts is highlighted for the preparation of enantiopure 2,2,3,4,5,6-hexasubstituted piperidine and tetrahydropyran from toluene.

Antifungal activity of a library of cyclitols and related compounds

The antifungal activity of a library of 32 cyclitols and derivatives, including 6 previously unreported cyclitol amino acid conjugates, was studied against the clinically important yeasts Candida albicans, Candida tropicalis and Cryptococcus neoformans along with Saccharomyces cerevisiae. Bioautography followed by standardized microbroth dilution methods were used and allowed to identify an azidoinositol glycoside (11) and an azidoconduritol linked to an aromatic aldehyde (18) as promising compounds. The results suggest the relevance of exploring synthetic cyclitolic structures as potential antifungal leaders.

Chemoenzymatic synthesis of trans -tetrahydrofuran cores of annonaceous acetogenins from bromobenzene

Two types of trans-THF cores, present in acetogenins, have been synthesized by an intramolecular iodoetherification reaction. The starting alkenol was obtained in a few steps from a chiral cis-diol resulting from microbial oxidation of bromobenzene. The cyclization gave complete stereoselectivity for trans-THF cores with either (S,S) or (R,R) configurations at the THF chiral carbons.

Chemoenzymatic preparation of (6R)-5,6-dihydro-2H-pyran-2-one: A ubiquitous structural motif of biologically active lactones

A chemoenzymatic synthesis of an enantiopure 6-substituted 5,6-dihydro-2H-pyran-2-one using bromobenzene as a starting material is presented. This important structural motif is found in a large number of chiral lactones that present a wide range of biological activities. The key features of the preparation include enzymatic dioxygenation of bromobenzene using Escherichia coli JM109 (pDTG601), microwave-assisted acyloin cleavage, and tin mediated lactonization. The stereochemical assignment for the alcohol was confirmed by NMR analysis of Moshers derivatives.

Chemoenzymatic synthesis of a mixed phosphine-phosphine oxide catalyst and its application to asymmetric allylation of aldehydes and hydrogenation of alkenes

The chemoenzymatic synthesis of a Lewis basic phosphine-phosphine oxide organocatalyst from a cis-dihydrodiol metabolite of bromobenzene proceeds via a palladium-catalysed carbon-phosphorus bond coupling and a novel room temperature Arbuzov [2,3]-sigmatropic rearrangement of an allylic diphenylphosphinite. Allylation of aromatic aldehydes were catalysed by the Lewis basic organocatalyst giving homoallylic alcohols in up to 57% ee. This compound also functioned as a ligand for rhodium-catalysed asymmetric hydrogenation of acetamidoacrylate giving reduction products with ee values of up to 84%.

Development of oseltamivir phosphonate congeners as anti-influenza agents

Oseltamivir phosphonic acid (tamiphosphor, 3a), its monoethyl ester (3c), guanidino-tamiphosphor (4a), and its monoethyl ester (4c) are potent inhibitors of influenza neuraminidases. They inhibit the replication of influenza viruses, including the oseltamivir-resistant H275Y strain, at low nanomolar to picomolar levels, and significantly protect mice from infection with lethal doses of influenza viruses when orally administered with 1 mg/kg or higher doses. These compounds are stable in simulated gastric fluid, liver microsomes, and human blood and are largely free from binding to plasma proteins. Pharmacokinetic properties of these inhibitors are thoroughly studied in dogs, rats, and mice. The absolute oral bioavailability of these compounds was lower than 12%. No conversion of monoester 4c to phosphonic acid 4a was observed in rats after intravenous administration, but partial conversion of 4c was observed with oral administration. Advanced formulation may be investigated to develop these new anti-influenza agents for better therapeutic use.