Evans’ anti reduction

Syn selective reductions Anti selective reductions The Evans-Tishchenko reduction Kinetic diastereoselection of 1,3-diols Aldol revisited... 

SCHEME 2.145 Saksena-Evans reduction and Menche one-pot anti-reduction. 

The final C—C bond forming step turned out to be a mismatched boron enolate aldol reaction. Nevertheless, the use of (-l-)-DIPCl as a stereochemical inducer guaranteed the disposition for reagent control versus substrate control. Required product 324a was isolated in approximately 60% yield after chromatography on reverse-phase silica gel. The Evans group anti-reduction of the newly obtained aldol product gave substance 325, which was totally deprotected... 

Diastereoselective reduction by chemical methods For the preparation of both enantiomers of dihydroxy ester sy -5a Prasad s [19] sy -selective borohydride reduction was applied, giving dihydroxy esters syn-5a in a diastereomeric ratio of dFsy a ti = 28 1 to 45 1. The enantiomers of dihydroxy ester anti-Sa were synthesized according to Evans method [20], which resulted in dr = 14 1 to 18 1... 

Fig. 13.1 Cytoprotective action of adenosine in a quantitative model of mouse hindlimb ischemia and reperfusion (I/R) injury. Adult wild type mice were injected with (a) sterile vehicle (0.1% DMSO in phosphate-buffered saline, pH 7.4) or various adenosine receptor agonists (b, c) or antagonist (d, f). (a) Following ischemia and reperfusion, skeletal muscle showed a significant uptake of Evans Blue dye (EBD) in vehicle-treated mice (first part of (a), representative of 7 mice). The contra-lateral leg not subjected to ischemia-reperfusion showed virtually no EBD uptake. In the second part of (a), the same section was stained with rabbit polyclonal anti-skeletal muscle actin antibodies followed by staining with goat anti-rabbit IgG conjugated with FITC. (b) The nonselective adenosine agonist R-PIA caused a large reduction in the EBD-stained area (see both first and second parts to this figure, representative of six mice)...

In 1986, Evans and colleagues introduced tetramethylammonium triacetoxyboro-hydride, a mild reducing reagent for the highly diastereoselective synthesis of 1,3-anft-diols from acyclic (3-hydroxy ketones1 (Scheme 4.2a). The reaction, commonly called the Evans-Chapman-Carreira reduction, is typically carried out in a 1 1 mixture of anhydrous acetic acid and acetonitrile, as the reaction needs to be run at low temperature in the presence of acetic acid. An important observation is that the anti -diastereoselectivity is realized regardless of the stereochemistry of the a-alkyl substituent Both anti - and. vvn-a.-methyl-(3-hydroxy... 

To explain the high levels of anti-selectivity, Evans and Hoveyda proposed that the reduction occurs through a hydride-bridged six-membered transition... 

The stereoselective reduction of the ketone function of 9 leads to a direct entry to selectively protected aldopentoses ( inversion strategy ) (Borysenko et al. 1989), which greatly expand the potential of this new protocol (Scheme 5). Following Evans protocol the tetramethylammo-nium triacetoxyborohydride-mediated reduction provides the yyn-diol 15 constituting a protected D-ribose (95%, >96% de). The anti-selective reduction to 17 was obtained after silyl protection of the free hydroxyl group of 9 to the OTBS-ether 16 using L-selectride. The aldopentose 18 was then accessible via chemoselective acetal cleavage followed by in situ cyclization (47% over two steps, >96% de). 

Evans, D. A., Hoveyda, A. H. Samarium-catalyzed intramolecular Tishchenko reduction of 3-hydroxy ketones. A stereoselective approach to the synthesis of differentiated anti 1,3-diol monoesters. J. Am. Chem. Soc. 1990, 112, 6447-6449. 

We referred above to a synthesis of bryostatin that contained a reduction controlled by a 1,3-relationship. Evans synthesis34 contains a 1,3-selective aldol as well as a 1,3-controlled reduction The aldehyde 202, made by an asymmetric aldol reaction, was combined with the double silyl enol ether of methyl acetoacetate to give, as expected, the anti-aldol 203. However, the only Lewis acid that gave this good result was (<-PrO)2TiCl2 and not BF3 thus emphasising the rather empirical aspect of this type of control. Evans s own 1,3-controlled reduction gave the anti,anti-triol 204 that was incorporated into bryostatin. 

C-8 was controlled by Evans reduction (58) of the 3-hydroxyketones 236 giving the anti 1,3-diols 237. The y-silyloxyallenes 238 were then subjected to a one-pot procedure already developed by... 

Heparin causes a reduction in mitotic index and a decrease in tumour volume for Ehrlich ascites tumours in mice . Polyethylene sulphonates having molecular weights between 15,000 and 35,000, also have antineo-plastic activity in mice against ascites tumours, carcinomas and leukaemias . Heparin has been found to reduce markedly the number of pulmonary metastases in rats receiving intravenous Walker 256 carcinoma cells . Evans blue in the presence of a sulphated pectin entered tumour cells but not normal tissue cells s. The anti-immunochemical action of heparin has been used successfully for tumour heterografts Ass. 

The Evans aldol reaction using chiral p-keto imide 23 as a dipropionate building block is also very effective for the construction of polypropionate segments in polyoxomacrolides (Scheme 2) [8]. The diastereoselective aldol reaction of 23 via different metal enolates (Ti, Sn, and B enolates) afforded three kind of aldols, syn-syn-24, anti-syn-25, and anti-anti-26, with high diastereoselectivity, respectively. The subsequent stereoselective reduction of the resulting p-hydroxy ketones 24-26 provides various types of dipropionate units. Based on this strategy, the... 

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