2- ethanols, from reductive ring

The earliest, and most complex, protocol is presented by Burgess and cowoikers [66]. Starting from aspartic acid dimethylester, the amino group is acylated by adamantyl carboxylic acid chloride (see Figure 6.26). Reduction of the two ester groups, but not the amide function, with NaBH in ethanol followed by ring closure yields an oxazolineto-sylate that is transformed into the iodide. 

Reduction with isolated enzymes avoids difficulties associated with diffusion limitations and also avoids the presence of many different enzymes, present in the whole cell, which can cause side reactions or reduced enantioselectivity. The main drawback, however, is the instability of the isolated enzyme and the requirement for added co-factor NAD(H) or NADP(H), which are the oxidized (or reduced) forms of nicotinamide adenine diphosphate or its 2 -phosphate derivative. These co-factors are expensive, but can be used as catalysts in the presence of a co-reductant such as formate ion HCOO or an alcohol (e.g. isopropanol or ethanol). The reduction of ketones occurs by transfer of hydride from the C-4 position of the dihydropyridine ring of NADH or NADPH (7.105). Only one of the two hydrogen atoms is transferred and this process occurs within the active site of the enzyme to promote asymmetric reduction. 

Hydrogenation of PDPB was best accomplished by chemical means, by the reduction of the stilbene type double bond of PDPB with potassium and ethanol. Quantitative reduction was achieved without affecting the saturation of the phenyl rings. Catalytic hydrogenation, primarily with noble metal catalysts under various conditions caused not only reduction of the chain double bond but also partial hydrogenation of the phenyl rings. The chemical reduction of the double bonds in PDPB was stereospecific as one would expect from a stilbene-type reduction and the structure of H-H PS consisted of about a 45% three and 55% erythro linkages in the polymer. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

A special technique was necessary to obtain good yields of ethyl pyrrole-3-acetate from ethyl pyrrole-3-glyoxalate. Reduction over W-7 Raney Ni in 50% aq ethanol was accompanied by major ring reduction and tarring. By use of a two-phase system, toluene and 50% aq ethanol, these side reactions could be curtailed. Apparently the desired product was removed effectively from the aqueous layer into the toluene as soon as it was formed (26). 

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