Epimerisation

This looks a Diels-Alder product, but the stereochemistry is wrong. However, the centre next to the C=0 can be epimerised in base so ... 

The new /-hydrastine is considered to be /-a-hydrastine and natural hydrastine to be /- -hydrastine, which implies (1) that the latter differs from natural narcotine (/-a-narcotine) in stereochemical configuration (2) that since a-gnoscopine, but not -gnoscopine, can be resolved, the synthesis of natural hydrastine will involve the deracemisation of hydra-stine-b, to /-a-hydrastine, which can be epimerised to natural hydrastine (/- -hydrastine) by boiling with methyl-alcoholic potassium hydroxide. 

There is also for the quinidine ether oxide group (formula C) an im-expected third isomeride, possibly due to epimerisation about carbon atoms 9 and 10. These quinidine isomerides are no doubt convertible... 

The third and fourth isomerides, viz., the two aZZosolanidanols, were prepared from solanidone (A Solatubenone of Roehelmeyer A -solaniden-3-one), already deseribed (p. 663), by hydrogenation with platinised Raney niekel in an alkaline medium. The reaetion produet yielded aZZosolanidan-3(a)-ol and aZZosolanidan-3(jS)-ol. R probably also ineluded the two solanidanols sinee the unerystallisable residue on epimerisation by sodium in boiling xylene followed by preeipitation with digitonin, yielded some solanidan - 3( j8 )-ol. 

Fluorinated dithioester 39 has also been involved in thioacylation reaction of enantiopure aminoalcohols leading to the corresponding hydroxylated thioamides. The later, treated either by SOCVpyridine, CH3SO2CI, or PhjP/DEAD, cyclise into thiazolines 42 without epimerisation and in excellent yields. An interesting application of this reaction is the synthesis of a new type of modified nucleotides such as 43 and 44 by a one pot reaction simply by mixing the dihydroxy substituted thioamide (obtained from 39 and the 2-amino-l,3-... 

Neither chiral centre in (1) can be epimerised by acid orbase, but a reverse Michael reaction, which should happen in base, provides both a suitable disconnection and a way to epimerise one chiral centre. 

WANG H and HELLiWELL K (2000) Epimerisation of catechins in green tea infusions . Food Chem, 70, 337 4. 

Possible racemisation of imines, derivatives of amino acids and R(—)-myrtenal, has been examined by Dufrasne et al.1 After 72 h, no significant effect on chiral purity was observed. For imines being derivatives of chiral primary amines and the a-substituted 8-keto-aldehydes, no evidence of epimerisation has been indicated by the NMR measurements.3 For a series of imines, being derivatives of amino acids or amino acid esters and (R)-BINOL reagents, Chin et al.5 have tested the possibility of epimerization under experiment conditions. It was shown that R S ratio has changed only slightly, and after 24 h, the difference was lower than 10%. 

Brunner et al.98-100 have published a series of papers on epimerisation of chiral rhodium(III) and iridium (III) half-sandwich complexes [39]. 

The kinetic studies of epimerisation were based on the integration of the signals at —35, 50 and 65 °C. The activation enthalpies and entropies... 

Boehm et al.100 have synthesised and studied a series of half-sandwich rhodium (III) and iridium (III) complexes, derivatives of salicylaldehyde and L-amino acid esters. The diastereoselectivity has shown strong dependence on the type of metal as well as amino acid residue. The labile configuration of the metal atoms was suggested because of changes in the diastereomers ratio with increasing temperature. Fast epimerisation at the metal atom was suggested for some S-phenylalanine complexes. 

Titanium tetrachloride-catalysed Michael additions of trimethylsilyl enol ethers to artemisitene afforded a neat route to 14-substituted artemisinin derivatives of type 125 (eg. R = allyl) and to 9-epiartemisinin derivatives 126 some of these compounds were more active against Plasmodium falciparum than artemisinin <00BMCL1601>. A series of 11-azaartemisinins also have better activity than artemisinin <00BMC1111>. On the other hand, epiartemisinin, prepared by base-catalysed epimerisation of artemisinin, has been shown to have poor antimalarial activity <00HCA1239>. 

R2. Robichon-Szulmajster, H. de, Sur un nouveau mecanisme d oxydo-reduction, appliqu6 a la reaction d epimerisation uridine diphosphogalactose = uridine diphos-phoglucose. J. Mol. Biol. 3, 253-256 (1961). 

Coupling Activation method Solvent Reaction time % Epimerisation in product... 

Several, optically pure imino sugars have been synthesised by Fleet25 from simple mono-saccharides in a short, high yield synthetic sequences. The novelty of the presented approach involved an application of benzhydryl protecting group which allowed to avoid epimerisation at C-2 (Fig. 14). 

But when a molecule contains two or more asymmetric carbon atoms and the configuration of only one is inverted, the process is called epimerisation. 

NL Benoiton. Sometimes it is neither a racemisation nor an epimerisation but an enantiomerisation. A plea for preciseness in the use of terms describing stereomutations in peptide synthesis. Int J Pept Prot Res 44, 399, 1994. 

The enantioselectivity determining step. Above we learnt that the oxidative addition of hydrogen is the rate-determining step. This step is irreversible and it also determines the enantioselectivity. This complex could still epimerise via substrate dissociation, but apparently it does not and migratory insertion is faster than epimerisation. We remember that two diastereomeric intermediates are involved, the major and the minor species and the minor species is the... 

Many of the older bis-indenyl catalysts are less selective at higher temperatures, which was ascribed initially to a lower selectivity of the insertion reaction itself. More recent work by Busico, based on deuteration studies and again based on very detailed and elegant analysis of 13C NMR spectra of the polymers, has shown that in fact epimerisation of the growing alkyl chain occurs via a series of (3-hydride eliminations and re-insertion reactions [36] involving even tertiary alkyl zirconium species. 

The use of deuterium labels in propene can help to establish the epimerisation of the intermediate alkyl species. 

When the allyl group is part of a cyclic structure, a k-g reaction cannot take place to epimerise one of the chiral carbon atoms after having formed the k-g intermediate, the same Jt-face comes back-on to palladium. Thus, if we start from a racemic cyclic alkenyl acetate mixture, racemisation at the complex is blocked and the product will also be a racemate at 100% conversion. Kinetic resolution is still an option to obtain chiral product and starting material. Nevertheless high ee s were obtained when cyclic alkenyl acetates were used. 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

At this stage of the synthesis, it was necessary to resort to a second conformational control element (shifting the B ring from a chair-chair to a boat-chair conformation), which ensures the generation of the C(l)-C(2) enolate of a C(2) ketone and allows the epimerisation of the substituent at C(3)a (which will return the B ring to the chair-chair conformation). 

Barbas, one of the pioneers of enamine catalysis, has incorporated iminium ion intermediates in complex heterodomino reactions. One particularly revealing example that uses the complementary activity of both iminium ion and enamine intermediates is shown in Fig. 12 [188]. Within this intricate catalytic cycle the catalyst, L-proline (58), is actively involved in accelerating two iminium ion catalysed transformations a Knoevenagel condensation and a retro-Michael/Michael addition sequence, resulting in epimerisation. 

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