Frances M. Brown

(S)-α-methoxyphenyl acetic acid : a new NMR chiral shift reagent for the stereochemical analysis of sulfoxides

Abstract The use of ( S )- α -methoxyphenyl acetic acid (MPAA) as a general chiral 1 H NMR shift reagent for the stereochemical analysis of sulfoxides is demonstrated. Using this methodology, both the enantiomeric purity and the absolute configuration of a wide variety of sulfoxides can be determined.

Biotransformation of organic sulfides. Part 7. Formation of chiral isothiocyanato sulfoxides and related compounds by microbial biotransformation

Abstract The fungi Helminthosporium species NRRL 4671 and Mortierella isabellina ATCC 42613 have been used for the biotransformation of a series of isothiocyanatoalkyl methyl sulfides and their synthetic precursors, ω-(methylthio)alkylphthalimides. H . species gave predominantly ( S ) sulfoxides in all cases; M. isabellina gave ( R ) isothiocyanatoalkyl methyl sulfoxides, but in the case of two ω-(methylthio)alkylphthalimides substantial conversion of sulfoxide to sulfone resulted in the isolation of the former with predominat ( S ) configuration. A correction is made of the previously reported configurations of two biotransformation products (Tetrahedron: Asymmetry, 1994 , 5 , 1129).

Biocatalytic and chemical routes to all the stereoisomers of methionine and ethionine sulfoxides

Abstract Biotransformations of the N-phthaloyl derivatives of d - and l -methionine and of d - and l -ethionine by Beauveria bassiana ATCC 7159 or Beauveria caledonica ATCC 64970 produce the corresponding (SS) sulfoxides in good yield and diastereomeric excess. Pure (SSSC) diastereomers can be obtained from l -series substrates by crystallisation of the biotransformation extract, and the corresponding (SSRC) products obtained from d -series substrates by chromatography of the biotransformation extract. Hydrogen peroxide-catalysed oxidation of the N-phthaloyl derivatives of d - and l -methionine and of d - and l -ethionine gives diastereomeric mixtures from which the (SSSC) and (RSRC) diastereomers can be obtained by crystallisation, and the (SSRC) and (RSSC) diastereomers obtained by chromatography. N-Cbz- and N-t-Boc methionines are also converted to sulfoxides with predominant (SS) configuration by both B. bassiana and B. caledonica, but the isolated yields and d.e. of products were generally lower than those obtained from the N-phthaloyl substrates. Removal of the N-phthaloyl group from diastereomerically pure methionine and ethionine sulfoxides gave the corresponding amino acid sulfoxides in high yield; removal of N-Cbz and N-t-Boc groups from protected methionine sulfoxides was also achieved without loss of configuration at sulfur.

Biotransformation of organic sulfides—VII. A predictive model for sulfoxidation by Helminthosporium species NRRL 4671

Abstract The fungus Helminthosporium species NRRL 4671 converts a wide range of prochiral sulfides to the corresponding chiral sulfoxides, the majority of which have ( S ) configuration at sulfur. The formation of a series of chiral cyclopentyl alkyl, cyclohexyl alkyl, benzyl alkyl, and methyl alkyl sulfoxides by biotransformation of the corresponding sulfides using Helminthosporium species is described. The analysis of over 90 such biotransformations has resulted in the development of a model based on restrictive space descriptors that has been used to rationalize these reactions, and that is proposed as a predictor of the outcome of Helminthosporium -catalyzed sulfoxidations.

Biotransformation of organic sulfides-IV. Formation of chiral benzyl alkyl and phenyl alkyl sulfoxides by Helminthosporium species NRRL 4671

The fungus Helminthosporium species NRRL 4671 has been used for the biotransformation of a series of phenyl alkyl sulfides with alkyl groups ranging from methyl to n-hexyl, and benzyl alkyl sulfides with alkyl groups from methyl to n-nonyl. Several 2-phenylethyl and 3-phenylpropyl sulfides have also been examined as substrates, together with cyclohexyl methyl sulfide and 1- and 2-naphthyl methyl sulfides. For the majority of substrates, sulfoxide formation occurred in moderate yield and with predominant (S) chirality at sulfur; lesser amounts of sulfone product were also obtained in some cases. The data so obtained have been used to define the preparatively useful limits of S-oxidation of phenyl alkyl sulfides and benzyl alkyl sulfides by biotransformation using Helminthosporium.

Biocatalytic and chemical preparation of all four diastereomers of methionine sulfoxide

Abstract Biocatalytic or chemical oxidations can be used in a complementary manner for the preparation of all four diastereomers of methionine sulfoxide with high diastereomeric purity in overall isolated yields of 20–55% from methionine. The N-phthaloyl derivatives of L- and D-methionine were selectively oxidised to the ( S S S C ) and ( S S R C ) sulfoxides respectively by biotransformation using the fungus Beauveria bassiana ATCC 7159. Hydrogen peroxide oxidation of the same materials gave mixtures from which the ( S S S C ) and ( R S R C ) isomers can be readily isolated by crystallisation. Chromatography of the residual material then afforded the ( R S S C ) and ( S S R C ) isomers.

Preparation of (R)-sulforaphane by biotransformation using Helminthosporium species NRRL 4671

Abstract The fungus Helminthosporium species NRRL 4671 oxidizes 1-isothiocyanato-4-(methylthio)butane to (−)-1-isothiocyanato-(4R)-(methylsulfinyl)butane (sulforaphane). Helminthosporium also converts 1-methylthio-4-(N-phthalimidyl)butane to the (R) sulfoxide.

Biotransformation of sulfides by Rhodocoeccus erythropolis

A version of Rhodococcus erythropolis IGTS8 BKO-53, designed as a model system for the biodesulfurization of crude oil with a high conversion activity of dibenzothiophenes to the corresponding sulfoxides has been used for oxidation of a large number of simple sulfides. A large variety of sulfides were converted to chiral sulfoxides in good yield. Sulfoxide stereoisomers were generally formed as (R) configuration in moderate stereochemical purity, but the sulfoxide diasteromers of methionine amino acid derivatives were produced at >90% optical purity.

Biocatalytic oxidation of S-alkylcysteine derivatives by chloroperoxidase and Beauveria species

Abstract Treatment of N -methoxycarbonyl C -carboxylate ester derivatives of S -methyl- l -cysteine by chloroperoxidase (CPO)/hydrogen peroxide resulted in oxidation at sulfur to produce the ( R S ) sulfoxide in moderate to high diastereomeric excess (DE). The ( S S ) natural product sulfoxide chondrine was obtained via biotransformation of the N -t.boc derivative of l -4-S-morpholine-2-carboxylic acid using Beauveria bassiana or Beauveria caledonica .

Formation of 5α steroids by biotranformation involving the 5α-reductase activity of Penicillium decumbens

The biotransformation of a series of delta 4-3-ketosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the 5 alpha-dihydrosteroid was observed for several substrates of the androstene and pregnene series: the reaction is tolerant of non-polar substituents (Cl and CH3) at C-4 of the substrate, but does not occur in the presence of a 4-hydroxyl group, or with additional unsaturation at the delta 1 or delta 6 positions. A-nor-, B-nor-, 3-deoxy-, and 3,5-cycloandrostanes are not reduced, but 6-methylenetestosterone is converted to a 6-methylene-5 alpha-dihydro derivative. Several biotransformations are reported which involve oxidoreductase activity at C-3 and/or C-17, either concomitant or independent of delta 4 reduction: the substrate specificity of the oxidoreductase processes has been examined and defined by the use of 3 alpha-hydroxy, 3 beta-hydroxy, 3-keto, 17 beta-hydroxy and 17-keto substituted steroids. In this way, the existence in P. decumbens of 3 beta-hydroxy-3-keto and 17 beta-hydroxy-17-keto oxidoreductases has been demonstrated.