Reduction of 2-Substituted Cyclohexanones by Saccharomyces Cerevisiae

An enzymatic reduction of 2-substituted cyclohexanones mediated by Saccharomyces cerevisiae was studied with respect to the stereochemical course and optical purity of the products. Reduction of ketones 1b-1f resulted in separable diastereoisomeric mixtures of cis- and trans-stereoisomers of 2-substituted cyclohexanols (2b-2f and 3b-3f) having the (S) absolute configuration at the chiral center bearing the hydroxyl functionality with high enantiomeric purity. Reduction of ketone 1a yielded mixture of cis-(1S, 2R)- and trans-(1R, 2R)-stereoisomers (2a and 3a) with lower enantiomeric purity. Changes in the nature of the C(2)-substituent affect the stereochemical course of the biotransformation. However, they significantly influenced the enantiomeric purity of the products. The diastereoselectivity of the process was studied as well; high diastereoselectivity was observed with the substrates 1a, 1e and 1f.     

Stereochemistry of the Enzymatic Reduction of 2-(4-Methoxybenzyl)-1-Cyclohexanone by Solanum Aviculare Cells in vitro

During the investigation of chemical properties of the dicyclic system of insect juvenile hormone analogues, biotransformation of 2-(4-methoxybenzyl)-1-cyclohexanone (1) by plant cell cultures was studied. Among other components, the cis-(1S, 2S)- and cis-(1R, 2R)-2-(4-methoxybenzyl)-1-cyclohexanol enantiomers 2a and 2b were found in the reaction mixture. Higher stereoselectivity of the biotransformation was observed for trans-(1S, 2R)-enantiomer 3a formation, which occurred in at least 60% of calculated enantiomeric excess.     

Enantioselectivity in the Rabbit Liver Microsomal Biotransformation of Styrene and Phenylpropenes

The rabbit liver microsomal P-450 catalyzed oxidation of styrene (1a) and isomeric phenylpropenes, trans-1-phenylpropene (1b), cis-1-phenylpropene (1c) and 3-phenylpropene (1d), was investigated and the enantioselectivity of the epoxidation of the olefinic double bond was determined by checking the enantiomeric excesses of the corresponding first formed epoxides (2). These enantiomeric excesses were always modest, ranging between 7% of (1S,2S)-(2b) and 22% of (1R,2R)-(2c). In the case of (1d) a nonenantioselective hydroxylation at the benzylic-allylic C(3) was also oberved. The ratio between this hydroxylation and olefin epoxidation of (Id) was 1:2.     

Microbial reduction of cyclohexanones

A Brazilian strain of the bacteria Serratia rubidaea CCT 5742 quantitatively reduced 4-tert-butylcyclohexanone and 4-methylcyclohexanone to the less thermodynamically stable diastereoisomeric alcohols cis-4-tert-butylcyclohexanol and cis-4-methylcyclohexanol with a diastereoisomeric excesses (de) of 96% and 44%, respectively. 2-Methylcyclohexanone was also totally reduced to the corresponding alcohols affording the trans-(+)-(1S, 2S)-2-methylcyclohexanol with 78% of de and an enantiomeric excess (ee) of 80%. The cis-(+)-(1S, 2R)-2-methylcyclohexanol was obtained in 98% ee.     

Reactions of the haloalcohols HO(CH2)nCl (n = 2, 3) with platinum(II) - alkynyl and -alkyne complexes. X-ray crystal structure of trans-[Pt(Me) {C(OCH2CH2Cl) (CH2Ph)} (PPh3)2] [BF4]

The chloro complexes trans-[Pt(Me)(Cl)(PPh₃)₂], after treatment with AgBF₄, react with 1-alkynes HC---C---R in the presence of NEt₃ to afford the corresponding acetylide derivatives trans-[Pt(Me) (C---C---R) (PPh₃)₂] (R = p-tolyl (1), Ph (2), C(CH₃)₃ (3)). These complexes, with the exception of the t-butylacetylide complex, react with the chloroalcohols HO(CH₂)_nCl (n = 2, 3) in the presence of 1 equiv. of HBF₄ to afford the alkyl(chloroalkoxy)carbene complexes trans-[Pt(Me) {C[O(CH₂)_nCl](CH₂R) } (PPh₃)₂][BF₄] (R = p-tolyl, N = 2 (4), N = 3 (5); R=Ph, N = 2 (6)). A similar reaction of the bis(acetylide) complex trans-[Pt(C---C---Ph)₂(PMe₂Ph)₂] with 2 equiv. HBF₄ and 3-chloro-1-propanol affords trans-[Pt(C---CPh) {C(OCH₂CH₂CH₂Cl)(CH₂Ph) } (PMe₂Ph)₂][BF₄] (7). T alkyl(chloroalkoxy)-carbene complex trans-[Pt(Me) {C(OCH₂CH₂Cl)(CH₂Ph) } (PPh₃)₂][BF₄] (8) is formed by reaction of trans-[Pt(Me)(Cl)(PPh₃)₂], after treatment with AgBF₄ in HOCH₂CH₂Cl, with phenylacetylene in the presence of 1 equiv. of n-BuLi. The reaction of the dimer [Pt(Cl)(μ-Cl)(PMe₂Ph)]₂ with p-tolylacetylene and 3-chloro-1-propanol yields cis-[PtCl₂{C(OCH₂CH₂CH₂Cl)(CH₂C₆H₄-p-Me}(PMe₂Ph)] (9). The X-ray molecular structure of (8) has been determined. It crystallizes in the orthorhombic system, space group Pna2₁, with a = 11.785(2), B = 29.418(4), C = 15.409(3) Å, V = 4889(1) ų and Z = 4. The carbene ligand is perpendicular to the Pt(II) coordination plane; the PtC(carbene) bond distance is 2.01(1) Å and the short C(carbene)-O bond distance of 1.30(1) Å suggests extensive electronic delocalization within the Pt---C(carbene)---O moietry.     

Enantiomers of cis- and trans-3-(4-propyl-cyclopent-2-enyl) propyl acetate. A study on the bioactive conformation and chiral recognition of a moth sex pheromone component

The enantiomers of cis- and trans-3-(4-propyl-cyclopent-2-enyl) propyl acetate, which are conformationally constrained analogues of (Z)-5-decenyl acetate (1), a sex pheromone component of the turnip moth, Agrotis segetum, have been synthesized and tested using the electrophysiological single-sensillum technique. The analogues mimic a cisoid and transoid conformation of 1, respectively. In addition, the enantiomers of each of the cis- and trans-isomers are conformationally constrained analogues of enantiomeric cisoid and transoid conformations of 1. Thus, the compounds prepared and tested are well suited to investigate the nature of the bioactive conformation of the natural pheromone component 1 and the chiral sense of its interaction with the receptor. Electrophysiological single-sensillum recordings show that the activity of the most active cis-isomer, which has a (1S,4R)-configuration, is more than two orders of magnitude higher than that of the most active trans-isomer. Furthermore, the (1S,4R)-isomer is at least 100 times more active than its enantiomer. These results strongly support a previously proposed cisoid bioactive conformation of 1. Furthermore, the (1S,4R)-configuration of most active stereoisomer identifies the chiral sense of the interaction between the natural pheromone component 1 and its receptor.     

Validated chiral high-performance liquid chromatographic method for the determination of trans-(−)-paroxetine and its enantiomer in bulk and pharmaceutical formulations

A stereospecific high-performance liquid chromatography method for the determination of trans-(−)-paroxetine and its enantiomer in bulk raw material and pharmaceutical formulations was developed and validated. The enantiomeric separation was achieved, without any derivatization, on a carbamate derivative-based column (Chiralpak AD). The effect of the organic modifiers, 2-propanol and ethanol, in the mobile phases was optimised to obtain enantiomeric separation. Limits of detection and quantitation of 2 and 6 ng, respectively, were obtained for both of the enantiomers. The linearity was established in the range of 5–41 μg for trans-(−)-paroxetine and in the range of 10–160 ng for trans-(+)-paroxetine. The accuracy of the method was 102.3% (mean value) for trans-(−)-paroxetine and 99.9% (mean value) for trans-(+)-paroxetine. For the precision (repeatability), a relative standard deviation value of 1.5% (mean value) for trans-(−)-paroxetine and of 2.1% (mean value) for trans-(+)-paroxetine was found. The method is capable of determining a minimum limit of 0.2% of trans-(+)-isomer in commercial samples.     

Probing conformations of the glycerol backbones of triacyglycerols in the active site of lipase by 1,2-cyclopentane-carbamates: The meso effect for the enzyme inhibition

The aim of this study is to probe the glycerol backbone conformation of the substrate (or inhibitor) in the active site of Pseudomonas species lipase by the 1,2-cyclopentandiol analogues of the ethylene glycerol carbamate inhibitors. Cyclopentane-carbamates, cis-1,2-di-N-n- butylcarbamyl-cyclopentane (1) and trans-1,2-di-N-n-butylcarbamyl-cyclopentane (2), are the conformationally constrained analogues of 1,2-di-N-n-butylcarbamyl ethane (3). All carbamates are synthesized and characterized as the pseudo-substrate inhibitors of the enzyme. Cis-cyclopentane-di-carbamate (1) is a more potent inhibitor than both ethane-di-carbamate (3) and trans-cyclopentane-di-carbamate (2) probably because the glycerol backbone conformations of cis-cyclopentane-di-carbamate (1) are constrained by the cyclopentane ring and cis-cyclopentane-di-cabamate (1) is a meso compound but trans-cyclopentane-di-carbamate (2) is a racemate.     

Syntheses and properties of organocyanamide, cyanoguanidine and dinitrogen complexes of rhenium. Crystal structure of mer-[ReCl2(NCNEt2) (PMePh2)3]

Treatment of a THF solution of trans-[ReCl(N₂)L₄] (L = PMePh₂) with a cyanamide, NCNR₂ (R = Me, Et or H) or with cyanoguanidine, NCNC(NH₂)₂ , yields mer-[ReCl(N₂)(NCNR₂)L₃] (1) or mer-[Re(N₂)[Re(N₂){NCNC(NH₂)₂}₂L₃]Cl (2), respectively, which, to our knowledge, are the first mixed dinitrogen-cyanamide-type complexes to be reported. The former products (1, R=Me or Et) can also be obtained from reaction of the benzoyldiazenido complex [ReCl₂(NNCOPh)L₃] with NCNR₂ in refluxing methanol; the Re(II) complex mer-[ReCl₂(NCNEt₂)L₃] (3) is also formed (conceivably via an unusual homolysis of the C---N bond of the benzoyldiazenido ligand) and its crystal structure is reported. It shows an unusual pyramidal conformation at the amine N atom of the diethylcyanamide ligand which also exhibits a significant structural trans influence on the phosphine, behaving as a stronger net electron donor than the latter ligand.     

Enhanced Resolution of a Secondary Alcohol by Hydrolysis of a Bichiral Ester Catalyzed by Lipase from Candida cylindracea

The effect of a chiral centre in the acyl group on the resolution of esters prepared from a racemic alcohol was investigated. R-2-chloropropionic acid afforded a higher enantiomeric ratio than S-2-chioropropionic acid in the hydrolysis of the corresponding esters of racemic 1-phenylethanol catalyzed by Candida cylindracea lipase. Even when a mixture of esters prepared from racemic acid and racemic alcohol was used for resolution of the alcohol, a noteworthy high enantioselectivity was observed. The hydrolysis of a bichiral ester offers an amplification in the resolution of enantiomers of alcohols by the combination of a chemical diastereoselectivity and an enzymatic enantio- and diastereoselectivity.     

Bioreduction of aromatic ketones: preparation of chiral benzyl alcohols in both enantiomeric forms

Substituted phenacyl chlorides are reduced with whole-cell biocatalysts to give (R)- or (S)-chlorohydrines in high yields and to make them good for high enantiomeric excess. Yields and enantiomeric purity of the S-enantiomer could be increased by performing bioreduction in the presence of polymeric absorbing resins. With this methodology, 2-chloro-1(S)-(3,4-dichloro-phenyl)-ethanol of 98% e.e. and 2-(R)-(4-nitro-phenyl)-ethanol of 92% e.e. have been prepared and used respectively as precursors in the synthesis of (+)-cis-1(S),4(S)-sertraline and of the β-blocker (R)-nifenalol®.     

Bis(mercapto) and hydrido(thiolate) complexes of Ru(II)–dppm (dppm=Ph2PCH2PPh2)

From a mixture of cis- and trans-Ru(SH)₂(dppm)₂ (4), formed from reaction of H₂S with trans-Ru(H)Cl(dppm)₂ (2), a crystal of cis-4 has been isolated and its structure determined by X-ray analysis. The mercapto protons are located within the centrosymmetric structure, although the S-atoms are partially disordered (S–H1.06 Å). The thiolate complexes, trans-Ru(H)SR(dppm)₂ (R=Ph, 5a; C₆F₅, 5b), have been isolated from reaction of trans-2 with 1 equiv. of RSH. trans-Ru(H)SH(dppm)₂ (3) has been isolated from reaction of H₂S with a mixture of cis- and trans-Ru(H)₂(dppm)₂ (1). An improved synthetic route for 1 is presented.     

Nitrogen atom transfer and redox chemistry of terpyridyl phosphoraniminato complexes of osmium (IV)

Rapid reactions occur between [Os^VI(tpy)(Cl)₂(N)]X (X = PF₆⁻, Cl⁻, tpy = 2,2′:6′,2″-terpyridine) and aryl or alkyl phosphi nes (PPh₃, PPh₂Me, PPhMe₂, PMe₃ and PEt₃) in CH₂Cl₂ or CH₃CN to give [Os^IV(tpy)(Cl)₂(NPPh₃)]⁺ and its analogs. The reaction between trans-[Os^VI(tpy)(Cl)₂(N)]⁺ and PPh₃ in CH₃CN occurs with a 1:1 stoichiometry and a rate law first order in both PPh₃ and Os^VI with k(CH₃CN, 25°C) = 1.36 ± 0.08 × 10⁴ M⁻ s⁻¹. The products are best formulated as paramagnetic d⁴ phosphoraniminato complexes of Os^IV based on a room temperature magnetic moment of 1.8 μ_B for trans-[Os^IV(tpy)(Cl)₂(NPPh₃)](PF₆), contact shifted ¹H NMR spectra and UV-Vis and near-IR spectra. In the crystal structures of trans-[Os^IV(tpy)(Cl)₂( NPPh₃)](PF₆)·CH₃CN (monoclinic, P2₁/n with a = 13.384(5) Å, b = 15.222(7) Å, c = 17.717(6) Å, β = 103.10(3)°, V = 3516(2) ų, Z = 4, R_w = 3.40, R_w = 3.50) and cis-[Os^IV(tpy)(Cl)₂(NPPh₂Me)]-(PF₆)·CH₃CN (monoclinic, P2₁/c, with a = 10.6348(2) Å, b = 15.146(9) ÅA, c = 20.876(6) Å, β = 97.47(1)°, V = 3334(2) ų, Z = 4, R = 4.00, R_w = 4.90), the long Os-N(P) bond lengths (2.093(5) and 2.061(6) Å), acute Os-N-P angles (132.4(3) and 132.2(4)°), and absence of a significant structural trans effect rule out significant Os-N multiple bonding. From cyclic voltammetric measurements, chemically reversible Os^V/IV and Os^IV/III couples occur for trans-[Os^IV(tpy)(Cl)₂(NPPh₃)](PF₆) in CH₃CN at +0.92 V (Os^V/IV) and −0.27 V (Os^IV/III) versus SSCE. Chemical or electrochemical reduction of trans-[Os^IV(tpy)(Cl)₂(NPPh₃)](PF₆) gives isolable trans-Os^III(tpy)(Cl)₂(NPPh₃). One-electron oxidation to Os^V followed by intermolecular disproportionation and PPh₃ group transfer gives [Os^VI(tpy)Cl₂(N)]⁺, [OS^III(tpy)(Cl)₂(CH₃CN)]⁺ and [Ph₃=N=PPh₃]⁺ (PPN⁺). trans-[Os^IV(tpy)(Cl)₂(NPPh₃)](PF₆) undergoes reaction with a second phosphine under reflux to give PPN⁺ derivatives and Os^II(tpy)(Cl)₂(CH₃CN) in CH₃CN or Os^II(tpy)(Cl)₂(PR₃) in CH₂Cl₂. This demonstrates that the Os^VI nitrido complex can undergo a net four-electron change by a combination of atom and group transfers.     

Reactivity of {(Ph3P)Pt[μ-η-H---SiH(Ar)]}2 (Ar=2-isopropyl-6-methylphenyl) with phosphines. X-ray crystal structure of trans-{(dppe)Pt[μ-SiH(Ar)]}2

The dinuclear Pt---Si complex {(Ph₃P)Pt{μ-η²-H---SiH(IMP)]}₂ (trans-1a–cis-1b=3:1; IMP=2-isopropyl-6-methylphenyl) reacted with basic phosphines such as 1,2-bis(diphenylphosphino)ethane (dppe) and dimethylphenylphosphine (PMe₂Ph) to afford different dinuclear Pt---Si complexes with loss of H₂, {(P)₂Pt[μ-SiH(IMP)]}₂ [P=dppe, trans-2a (major), cis-2b (trace); PMe₂Ph, 3 (trans only)]. Complexes 2 and 3 were characterized by multinuclear NMR spectroscopy and X-ray crystallography (2a). In contrast, the reaction of 1a,b with the sterically demanding tricyclohexylphosphine (PCy₃) afforded {(Cy₃P)Pt{μ-η²-H---SiH(IMP)]}₂ (trans-4a–cis-4b 2:1) analogous to 1a,b where the central Pt₂Si₂(μ-H)₂ core remains intact but the PPh₃ ligands have been replaced by PCy₃. Complexes 4a and 4b was characterized by multinuclear NMR and IR spectroscopies.     

Geometrical configuration of monomethyl–platinum(II) complexes driven by the size of entering nitrogen ligands

The reaction of the monoalkyl complex trans-[Pt(DMSO)₂Cl(CH₃)] with a large variety of heterocyclic nitrogen bases L, in chloroform solution, leads to the formation of uncharged complexes of the type [Pt(DMSO)(L)Cl(CH₃)], containing four different groups coordinated to the metal center. Only two out of the three different possible isomers were detected in solution. These two trans(C,N) and cis(C,N) species can be unambiguously identified through ¹H NMR spectroscopy. For the trans(C,N) isomers, average values of ²J_PtH=75±4 Hz and ³J_PtH=36±4 Hz have been observed for the coordinated methyl and DMSO ligands, respectively. In the case of the cis(C,N) isomers, these values increase to ²J_PtH=83±2 Hz, and decrease to ³J_PtH=26±3 Hz due to the mutual exchange of ligands in trans position to CH₃ and DMSO. In the case of bulky asymmetric ligands, such as quinoline, 2-quinolinecarboxaldehyde, 2-methylquinoline, 5-aminoquinoline, 2-phenylpyridine and 2-chloropyridine, slow rotation of the hindered group around the Pt---N bond makes the coordinated DMSO ligand prochiral. NMR experiments have shown that the first reaction product is the trans(C,N) isomer as a consequence of the very fast removal of one DMSO ligand by the nitrogen bases from the starting complex trans-[Pt(DMSO)₂Cl(CH₃)]. This trans kinetic product undergoes a geometrical conversion into the more stable cis(C,N) isomer through the intermediacy of fast exchanging aqua-species. The rate of isomerization and the relative stability of the two isomers depends essentially on the rate of aquation and on the steric congestion imposed by the new L ligand on the metal.     

Enzymatic synthesis of optically active 2-methyl- and 2,2-dimethylcyclopropanecarboxylic acids and their derivatives

Catalyzed by Rhodococcus sp. AJ270 microbial cells under very mild conditions, racemic 2,2-dimethylcyclopropanecarbonitrile (1) and its amide (2), and trans- and cis-2-methylcyclopropanecarboxamides (4) and (7) underwent enantioselective hydrolysis to give the corresponding optically active amides and acids.     

Effect of 4-hydroxytamoxifen isomers on growth and ultrastructural aspects of normal human breast epithelial (HBE) cells in culture

In the search for a breast cancer prevention strategy which would avoid undesirable effects of orally administered tamoxifen, the percutaneous administration of the highly active metabolite 4OHTamoxifen (4OHTam) has been proposed. Percutaneous 4OHTam penetrates the skin to reach breast tissues. It, thus, avoids the hepatic first pass effect, and offers an optimal local/systemic effect. However, trans-4OHTamoxifen can spontaneously isomerize into the cis-isomer, which may have estrogen agonist action. The aim of this study was to examine the effect of cis-4OHTam on normal human breast epithelial (HBE) cells in culture.

Spontaneous isomerization of trans- into cis-4OHTam occurred within 24–48 h, but stabilized rapidly at a trans/cis ratio of 70/30, whether in stock solution, culture medium or cultured cells. The cis-4OHTam did not stimulate HBE cell growth according to histometric cell counts and scanning electron microscopy analysis, but inhibited E₂-induced cell growth, albeit two to three times less than trans-4OHTam.

In conclusion, spontaneous isomerization of trans- to cis-4-OHTam is limited and 4OHTam retains a marked antiestrogenic effect. It may prove to be a useful alternative to tamoxifen in breast cancer prevention, especially if administered percutaneously.     

Slippage of η-allenyl/propargyl to an η structure and tautomerization of η-propargyl to η-allenyl in ligand addition and substitution reactions of platinum(II) complexes

Reactions of [(PPh₃)₂Pt(η³-CH₂CCPh)]OTf with each of PMe₃, CO and Br⁻ result in the addition of these species to the metal and a change in hapticity of the η³-CH₂CCPh to η¹-CH₂CCPh or η¹-C(Ph)=C=CH₂. Thus, PMe₃ affords [(PMe₃)₃Pt(η¹-C(Ph)=C=CH₂)]⁺, CO gives both [trans-(PPh₃)₂Pt(CO)(η¹-CH₂CCPh)]⁺ and [trans-(PPh₃)₂Pt(CO)(η¹-C(Ph)=C=CH₂)]⁺, and LiBr yields cis-(PPh₃)₂PtBr(η¹-CH₂CCPh), which undergoes isomerization to trans-(PPh₃)₂PtBr(η¹-CH₂CCPh). Substitution reactions of cis- and trans-(PPh₃)₂PtBr(η¹-CH₂CCPh) each lead to tautomerization of η¹-CH₂CCPh to η¹-C(Ph)=C=CH₂, with trans-(PPh₃)₂PtBr(η¹-CH₂CCPh) affording [(PMe₃)₃Pt(η¹-C(Ph)=C=CH₂)]⁺ at ambient temperature and the slower reacting cis isomer giving [trans-(PPh₃)(PMe₃)₂Pt(η¹-C(Ph)=C=CH₂)]⁺ at 54 °C . All new complexes were characterized by a combination of elemental analysis, FAB mas spectrometry and IR and NMR (¹H, ¹³C{¹H} and ³¹P{¹H}) spectroscopy. The structure of [(PMe₃)₃Pt(η¹-C(Ph)=C=CH₂)]BPh₄·0.5MeOH was determined by single-crystal X-ray diffraction analysis.     

Enzymatic evaluation of different Aspergillus strains by biotransformation of cyclic ketones

The potential of different Aspergillus strains in carrying out the biotransformation of cyclic ketones was investigated. All the strains employed showed alcohol dehydrogenase and Baeyer–Villiger monooxygenase activities. trans-2-Methylcyclohexanol and trans-4-methylcyclohexanol were prepared in a single isomeric form by the use of Aspergillus terreus SSP 1498 and the corresponding ketones. Baeyer–Villiger oxidation of cyclic ketones by all the fungi Aspergillus led to chiral lactones in good enantioselectivity.     

Conjugated linoleic acids: are they beneficial or detrimental to health?

Conjugated linoleic acids (CLAs) comprise a family of positional and geometric isomers of linoleic acid (18:2n − 6; LA) that are formed by biohydrogenation and oxidation processes in nature. The major dietary sources of these unusual fatty acids are foods derived from ruminant animals, in particular dairy products. The main form of CLA, cis-9, trans-11-18:2, can be produced directly by bacterial hydrogenation in the rumen or by delta-9 desaturation of the co-product vaccenic acid (trans-11-18:1) in most mammalian tissues including man. The second most abundant isomer of CLA is the trans-10, cis-12-18:2 form. Initially identified in grilled beef as a potential anti-carcinogen a surprising number of health benefits have subsequently been attributed to CLA mixtures and more recently to the main individual isoforms. It is also clear from recent studies that the two main isoforms can have different effects on metabolism and cell functions and can act through different cell signalling pathways. The majority of studies on body compositional effects (i.e. fat loss, lean gain), on cancer and cardiovascular disease attenuation, on insulin sensitivity and diabetes and on immune function have been conducted with a variety of animal models. Observations clearly emphasise that differences exist between mammalian species in their response to CLAs with mice being the most sensitive. Recent studies indicate that some but not all of the effects observed in animals also pertain to human volunteers. Reports of detrimental effects of CLA intake appear to be largely in mice and due mainly to the trans-10, cis-12 isomer. Suggestions of possible deleterious effects in man due to an increase in oxidative lipid products (isoprostanes) with trans-10, cis-12 CLA ingestion require substantiation. Unresponsiveness to antioxidants of these non-enzymatic oxidation products casts some doubt on their physiological relevance. Recent reports, albeit in the minority, that CLAs, particularly the trans-10, cis-12 isomer, can elicit pro-carcinogenic effects in animal models of colon and prostate cancer and can increase prostaglandin production in cells also warrant further investigation and critical evaluation in relation to the many published anti-cancer and anti-prostaglandin effects of CLAs.