•Dimerization, under Snider’s conditions, worked well with hydroxyanthracenones.•Mn-oxidation of hydroxynaphthalene carboxylates in benzene led to dimerization.•Mn-oxidation of hydroxynaphthalene led to oxidation or Wessely acetoxylation.•Wessely acetoxylation depends on reaction solvent and nature of substrates.Manganese-triacetate mediated oxidation of 1-hydroxy-2-napthalene carboxylates in benzene under anhydrous conditions delivers the dimerized product. However, acetoxylation on the ortho- or para-position, or oxidation to quinones occurs on the 1-hydroxy-3-substituted 2-napthalene carboxylates depending on the nature of the substituents when the reaction is carried out in a mixture of acetic acid/acetonitrile.Download high-res image (111KB)Download full-size image

The new 2-acetyl-8-methoxynaphthol (1) and five new “dimeric” napthopyranones, karwinaphthopyranones A1 and A2 (2 and 3) and karwinaphthopyranones B1–B3 (4–6), possessing a methoxy group at C-5′, were isolated together with four other known compounds from the dried fruits of Karwinskia parvifolia. The structures of compounds 2–6 were determined by spectroscopic data interpretation. Cell culture assays showed that some of these compounds possess antiproliferative activities in representative human cancer cell lines, with half-maximal growth inhibitory concentrations in the micromolar range.

Addition of both antipodes of 4-phenyl 1,3-oxazolidine-2-thione to 4-substituted N-crotonyl 1,3-oxazolidin-2-ones furnished Michael addition products. A perfect match occurred when both Michael donor and acceptor possessed the same stereochemistry and a mismatch when they had opposite stereochemistries. The newly created stereochemical center was shown to be governed by the Michael donor and not by the acceptor.

Conjugate addition of thiazolidinethiones and oxazolidinethiones to N-crotonylthiazolidinethiones and -oxazolidinethiones was observed in the presence of excess triethylamine in dichloromethane. The addition takes place by the nitrogen of the heterocycle with high diastereoselectivity. It was observed that the stereoselective addition occurs on the anti-s-cis conformation of the N-enoyl sulfur-containing heterocycle.

Addition of organocuprates, generated in situ using an excess of a 1:2 mixture of CuI·DMS and Grignard reagent, to N-enoyl oxazolidinethiones in the presence of excess TMSI gave preferentially the anti diastereomer where the addition took place when the conformation of the substrate was syn-s-cis. The reaction was investigated with indene-based and three different phenyl glycine derived oxazolidinethiones.

We have synthesized an analog of dehydroepiandrosterone (DHEA, 1) containing both a benzophenone (BP) and a biotin (Bt) group (DHEA–BP–Bt, 8). Compound 8 was prepared by functionalization on C-17 of 1. Biocytin was reacted with 4-benzoylbenzoic acid and the product was condensed with 1 containing a diamine–hexane linker. We detected specific protein bands of approximately 55, 80, and 150 kDa by SDS–PAGE analysis of vascular endothelial cell plasma membranes which had been photoirradiated in the presence of 8.A novel analog of DHEA, carrying both benzophenone and biotin groups, retains the biological activity of DHEA and can be used for analysis and isolation of cellular DHEA binding sites.

A green method for Baeyer–Villiger oxidation based on the chemo-enzymatic perhydrolysis of carboxylic acids and esters has been optimized using Novozyme-435, the immobilized form of Candida antarctica lipase B, and the complex urea–hydrogen peroxide (UHP) in ethyl acetate. This protocol previously employed for the chemo-enzymatic epoxidation of unfunctionalized olefins was shown to be effective for the Baeyer–Villiger oxidation of cyclohexanone and substituted cyclohexanones. The absence of water in the reaction media avoided any hydrolysis of the oxidized product. A minimum amount of enzyme was necessary to show the catalytic effect. The reaction yields of substituted ε-caprolactones varied depending on the nature of the substituent.

A green method for alkene epoxidation based on the chemo-enzymatic perhydrolysis of carboxylic acids and esters has been optimized using Novozyme 435, the immobilized form of Candida antarctica lipase B, and the complex urea–hydrogen peroxide (UHP). UHP, an anhydrous form of hydrogen peroxide, has the potential of releasing hydrogen peroxide in a controlled manner and thus avoids the need to add the aqueous hydrogen peroxide slowly to the reaction mixture. The absence of water in the reaction media was also beneficial, because it minimized undesired reactions of the oxidized products. A minimum amount of enzyme was necessary to show the catalytic effect. On recycling, the enzyme maintained its activity up to six rounds of epoxidations. A range of alkenes was epoxidized by this method providing yields ranging from 75 to 100 percent.

A highly enantioselective oxidation of benzhydrylsulfanyl acetic acid to the corresponding (S)-sulfinyl carboxylic acid was achieved employing the fungus Beauveria bassiana in very good yield. This product was amidated using the bacteria Bacillus subtilis to afford (S)-modafinil in good yield.(+)-(S)-(Diphenylmethanesulfinyl)acetic acidC15H14O3S[α]D22 = +38.3 (c 1.0, CH3OH)Ee: 99% (chiral HPLC)Absolute configuration: SsSource of chirality: microbial oxidation(+)-(S)-(Diphenylmethanesulfinyl)acetamideC15H15NO2S[α]D22 = +79 (c 1.0, CHCl3)Ee: 100% (chiral HPLC)Absolute configuration: SsSource of chirality: [(4R)-Phenyl-2-thioxo-thiazolidine-3-yl]-(S)-(diphenylmethanesulfinyl)acetamide

Both enantiomers of modafinil, adrafinil, modafinic acid and ethyl modafinate were prepared from the diastereomers formed by reacting racemic β-sulfinyl carboxylic acid with (4R)-phenyl-thiazolidinethione. The absolute stereochemistry of the sulfoxide group was confirmed via X-ray analysis of one of the thiazolidinethione diastereomers.(−)-[(4R)-Phenyl-2-thioxo-thazolidine-3-yl]-(R)-(diphenylmethanesulfinyl)acetamideC24H21NO2S3[α]D22=-230.4 (c 0.99, CHCl3)Source of chirality: chromatographic separation of diastereomersAbsolute configuration: 4R,R(−)-[(4R)-Phenyl-2-thioxo-thazolidine-3-yl]-(S)-(diphenylmethanesulfinyl)acetamideC24H21NO2S3[α]D22=-216.5 (c 1.0, CHCl3)Source of chirality: chromatographic separation of diastereomersAbsolute configuration: 4R,S(+)-(S)-(Diphenylmethanesulfinyl)acetamideC15H15NO2S[α]D22=+81 (c 1.0, CHCl3)Source of chirality: synthesis from (−)-[(4R)-phenyl-2-thioxo-thazolidine-3-yl]-(S)-(diphenylmethanesulfinyl)acetamideAbsolute configuration: S(+)-(R)-(Diphenylmethanesulfinyl)acetohydroxamic acidC15H15NO3S[α]D22=+14 (c 0.85, CH3OH)Source of chirality: synthesis from (−)-[(4R)-phenyl-2-thioxo-thazolidine-3-yl]-(R)-(diphenylmethanesulfinyl)acetamideAbsolute configuration: R(−)-(R)-(Diphenylmethanesulfinyl)acetic acidC15H14O3S[α]D22=-41.7 (c 1.0, CH3OH)Source of chirality: synthesis from (−)-[(4R)-phenyl-2-thioxo-thazolidine-3-yl]-(R)-(diphenylmethanesulfinyl)acetamideAbsolute configuration: R(−)-(R)-Ethyl (diphenylmethanesulfinyl)acetateC17H18O3S[α]D22=-58.5 (c 0.85, CHCl3)Source of chirality: synthesis from (−)-[(4R)-phenyl-2-thioxo- thazolidine-3-yl]-(R)-(diphenylmethanesulfinyl)acetamideAbsolute configuration: R

Chemo-enzymatic oxidation of cyclopentanones and substituted cyclopentanones to the corresponding δ-valerolactones was investigated employing catalytic amount of Candida antarctica lipase-B in ethyl acetate and employing urea–hydrogen peroxide as the oxidant. In contrast to the smooth oxidation of cyclohexanones to the corresponding ɛ-caprolactones, the δ-valerolactones reacted further with the lipase delivering trans-esterified products and also acetylated alcohols, depending on the structural nature of the cyclopentanones.