Asymmetric reduction of 2-substituted 2-butenolides with reductase from Marchantia polymorpha

A p68 reductase participating in the asymmetric reduction of the C–C double bond of 2-substituted 2-butenolides was isolated from Marchantia polymorpha. The enzyme reduced 2-substituted 2-butenolides to give (R)-butanolides, and the reduction of citraconic anhydride afforded (R)-methylsuccinic anhydride.     

Stereoselective reduction of chiral trans-3-acetyl-4-alkylpyrrolidin-2-ones

A number of trans-3-acetyl-4-alkylpyrrolidin-2-ones 8a–d and 11a,b were prepared and reduction of the keto group, carried out with KBH₄ in CH₃OH, led mainly to 3-hydroxyethylpyrrolidin-2-ones 13a–d and 19a,b with high stereoselection. Configuration of the newly formed stereogenic centre on the hydroxyethyl chain was assigned by ¹H NMR data supported by molecular mechanic calculations and eventually confirmed by X-ray diffraction analysis of p-iodobenzoate derivative 15.     

Stereoselective synthesis of enantiopure γ-aminoalcohols by reduction of chiral β-enaminoketones

The results of the reduction of chiral β-enamino ketones with sodium borohydride in acetic acid are reported. The reaction is convenient, stereoselective and high yielding and allows the preparation of enantiopure γ-amino alcohols in syn diastereoselectivity. The reaction is easy to perform and does not require expensive or hazardous chemicals. A mechanistic hypothesis is presented. The absolute configuration of the products obtained is attributed by correlating ¹H NMR spectral data with conformational analysis performed by molecular modelling, and confirmed by X-ray analysis.     

Stereoselective synthesis of (S)-dapoxetine: a chiral auxiliary mediated approach

An imidazolidin-2-one chiral auxiliary mediated acetate aldol reaction was explored in the enantioselective synthesis of (S)-dapoxetine (SSRI). The diastereoselective aldol adduct was transformed to highly enantiopure (S)-dapoxetine with overall good yield.     

Stereoselective synthesis of chiral 3,4,5-trisubstituted 1,5-dihydropyrrol-2-ones from azadienes

A new access to enantiopure 3-phthalimido-4-amino-5-(1-hydroxyalkyl) 1,5-dihydropyrrol-2-ones has been developed from 1,3-azadienes. Stereoselective Lewis acid catalyzed addition of a cyano group to an azadiene, followed by intramolecular ring closure, in a four-step one-pot synthesis, results in the formation of γ-lactams in satisfactory yields.     

Stereoselective aldol reactions of dihydroxyacetone derivatives catalyzed by chiral Zn2+ complexes

The direct aldol reaction between a protected dihydroxyacetone derivative and 4-nitrobenzaldehyde catalyzed by chiral Zn²⁺ complexes of 1-(n-carboxylalkyl)-7-aminoacyl-1,4,7,10-tetraazacyclododecane is reported. New Zn²⁺ complexes containing l-histidine and carboxylalkyl chains that mimic a class II aldolase, carboxypeptidase A and a serine protease were designed and synthesized. Syn-aldol products were mainly formed by an aldol reaction of acetonide-protected dihydroxyacetone with benzaldehydes and other benzaldehydes in N-methylpyrrolidone (NMP)/alcohol (MeOH, EtOH or 2-PrOH) in good yields with a high degree of diastereo- and enantioselectivity (56%～quant., 57～>99% ee). Mechanistic aspect based on ESI-HRMS, elemental analysis and pH titrations of model ligands is also discussed.     

Stereoselective |2+2| photocycloaddition of chiral 2(5H)-furanones to alkenes

The steric and stereoelectronic dependence of the diastereoselectivity in the photochemical |2+2| cycloaddition of chiral 2(5H)-furanones to alkenes is investigated to prepare eventually cyclobutanic natural products. It is shown that the alkenes approach to different chiral 5-substituted 2(5H)-furanones mainly by the less hindered side.     

Stereoselective synthesis of 3-substituted tetrahydroisoquinolines from phthalan and chiral N-sulfinylimines

The reaction of the dianionic intermediate [resulting from the reductive opening of phthalan (1) with lithium] with chiral N-tert-butylsulfinyl aldimines 3 in the presence of ZnMe₂ gives, after hydrolysis, N-tert-butylsulfinyl amino alcohols 4 with high diastereoselectivity. Successive treatment of compounds 4 with hydrogen chloride in methanol, thionyl chloride in chloroform and sodium hydroxide yields 3-substituted tetrahydroisoquinolines 6.     

Polyketides produced by Daldinia loculata cultured from Northern Manitoba

The fungus present in a soil sample collected from Northern Manitoba was cultured. The natural products produced by this organism were isolated and identified as the polyketides (1), (2), (3). A trace amount of the aromatic alcohol tyrosol (4) was also isolated. This organism was identified as Daldinia loculata by sequencing of the internally transcribed spacer region of the nuclear ribosomal DNA. The polyketides 1-3 were assayed against E. coli and it was observed that 1 displayed mild antibiotic activity.     

Stereoselective synthesis of oxiranes using oxazolidines derived from 2-amino-2-deoxy-d-allose as chiral auxiliaries

The synthesis of 2,3-epoxyamide derivatives of 2-amino-2-deoxy-d-allose is described. Epoxidation of the corresponding α,β-unsaturated amides with m-CPBA took place with better stereoselectivity when an oxazolidine ring was fused to the 2,3-positions of the sugar molecule. In most cases, both stereoisomers could be isolated and characterized. The stereochemistry of the new stereogenic centers was then determined by cleavage of the oxirane moiety from the chiral auxiliary, which was also recovered.     

Stereoselective Mannich-type reaction of chiral aldimines with 2-silyloxybutadienes by using trifluoromethanesulfonic acid

Novel stereoselective Mannich-type reaction of chiral aldimines with 2-silyloxybutadienes in the presence of trifluoromethanesulfonic acid has been carried out to give the corresponding products, which are not obtained by general Lewis acid-promoted methods, with 70-92% de in 62-74% yield. No cycloadducts were detected in the crude product by ¹H NMR.     

Stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucines

A stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucine is disclosed. The key step of the reaction sequence involves, stereo- and regioselective bromohydration of 7, using a brominating agent derived in situ from N-bromosuccinimide and 2,6-lutidine, via intramolecular sulfinyl group participation.     

Stereoselective synthesis of (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin

A stereoselective approach for the synthesis of (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin from l-ascorbic acid has been described. The key steps are highly stereoselective nucleophilic addition reaction on aldehyde 8 and also a single pot transformation of 15 to (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin. The later tandem reaction which involves the hydrogenation of double bond, debenzylation, MOM deprotection and bicyclic ketal formation was carried under Pd/C, H₂ followed by acid treatment.     

Stereoselective reduction of C=X by a chiral 1,4-dihydropyridine (NADH-MIMIC) in a self-immolative process

A series of prochiral ketones and a prochiral imine was reduced with high absolute stereoselectivity using an optically active 4-methyl-1,4-dihydropyridine in the presence of Mg(ClO₄)₂.     

Stereoselective electrogeneration of (E)-4-alkoxy-2-phenyl-5-chloro-2-oxazolines by cathodic reduction of N-(1-alkoxy-2,2,2-trichloroethyl)benzamides

The first method for the synthesis of the title compounds has been established. Quantitative reactions of benzamides with chloral hydrate provided chloralbenzamides which were efficiently converted to N-(1,2,2,2-tetrachloroethyl)amides by treatment with phosphorus pentachloride. These compounds reacted selectively with alcohols under mild conditions to give N-(1-alkoxy-2,2,2-trichloroethyl)benzamides in high yields which were stereoselectively transformed to (E)-4-alkoxy-2-aryl-5-chloro-2-oxazolines in fair to good yields by electrochemical reduction under constant cathodic potential in an aprotic medium.     

Enantioselective reduction of 2-substituted tetrahydropyran-4-ones using Daucus carota plant cells

Enzymatic reduction of 2-substituted tetrahydropyran-4-ones with Daucus carota, plant cells as biocatalyst occurred in water under extremely mild and environmentally benign conditions giving a 1:1 mixture of diastereoselectively (2R,4S)- and (2S,4S)-2-aryl- or 2-alkyl-tetrahydropyranols in high yields.     

Stereoselective reduction of alkyl 3-oxobutanoate by carbonyl reductase from Candida magnoliae

The enantioselective reduction of alkyl 3-oxobutanoates by carbonyl reductase (S1) from Candida magnoliae was investigated. S1 reduced alkyl 4-halo-3-oxobutanoates to the corresponding enantiomerically pure (S)-3-hydroxy esters. Escherichia coli HB101 transformant co-overproducing the S1 and glucose dehydrogenase from Bacillus megaterium, produced optically pure alkyl 4-substituted-3-hydroxybutanoates in a two-phase water/organic solvent system.     

Stereoselective determination of allethrin by two-dimensional achiral/chiral liquid chromatography with ultraviolet/circular dichroism detection

A two-dimensional achiral/chiral HPLC method with circular dichroism (CD) detection was optimized for the stereochemical resolution and determination of the elution order of the eight stereoisomers of synthetic allethrin. A monolithic silica HPLC column (Chromolith, Merck, 100 mm x 4.6 mm i.d.) was put orthogonally to an enantioselective OJ Daicel column (250 mm x 4.6 mm i.d.) by means of a switching valve. The resolution of cis and trans diastereoisomers on the silica column was obtained by using a mobile phase consisting of n-hexane:tert-butyl methyl ether (96:4) (v/v) at a flow rate of 1 ml min(-1). The cis and trans peaks were then switched to the enantioselective OJ column separately in two subsequent injections. The resolution of the four trans stereoisomers was accomplished by using n-hexane:tert-butyl methyl ether (90:10) (v/v), while the mobile phase composition for the four cis stereoisomers consisted of n-hexane:isopropanol (99.3:0.7) (v/v). The CD based detection system allowed the determination of the elution order on the basis of the CD signals of the single stereoisomers, together with the injection of pure stereoisomers. Under the final conditions, the validated method was applied to the determination of stereoisomeric composition and absolute configuration of the prevailing stereoisomers of real samples, i.e. commercial batches of different sources of d-allethrin.     

Diastereoselective reduction of β-keto carbonyl compounds by cultured plant cells

The diastereoselective reduction of β-keto carbonyl compounds such as 2-benzamidomethyl-3-oxobutanoates and 2-methyl-2-(2-propenyl)cyclopentan-1,3-dione by cultured cells of higher plants was investigated. The reduction of the 2-benzamidomethyl-3-oxobutanoates by Parthenocissus tricuspidata diastereoselectively produced the (2R,3S)-2-benzamidomethyl-3-hydroxybutanoates, whereas the reduction by Gossypium hirsutum gave the (2S,3S)-2-benzamidomethyl-3-hydroxybutanoates. The (2R,3S)/(2S,3S) predominance in the reduction with Nicotiana tabacum, Glycine max, and Catharanthus roseus was reversed by the change in the structure of the alkoxyl group in the substrate. On the other hand, the reduction of 2-methyl-2-(2-propenyl)cyclopentan-1,3-dione by P. tricuspidata produced (2R,3S)-3-hydroxy-2-methyl-2-(2-propenyl)cyclopentan-1-one, whereas the reaction by N. tabacum, G. max, C. roseus, and G. hirsutum gave (2S,3S)-3-hydroxy-2-methyl-2-(2-propenyl)cyclopentan-1-one.