Carboxyl groups, protection reduction

Thus, according to Scheme 28, (-)-shikimic acid 169 was converted to cyclohexadiene derivative 170 via esterification of carboxyl group, protection of the m-disposed hydroxyls, and elimination of the remaining carbinol moiety. Catalytic dihydroxylation of 170 gave unsaturated esters 171 and 172 as a separable 1 1 mixture. The 5,5a-unsaturated isomer 171 was finally elaborated into the desired (-)-MK7607 (174) via simple protection-reduction-deprotection sequence. 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

Nucleosides of glycuronic acids have been examined356 by 1H-n.m.r., o.r.d., and i.r. spectroscopy as suitable, model compounds of the rotamer states about the nucleosidic C-N bond. The carboxylate group on C-4 of an oxidized nucleoside has also been used357 as a protecting device its production from the nucleoside (by oxidative methods), and regeneration therefrom (by reduction with sodium... 

The enantioselective synthesis (51) of the side chain 30 of taxol had been achieved by way of stereospecific Sharpless epoxidation of cij-cinnamyl alcohol (29a), giving 29b (see Scheme 6). Following oxidation of the alcohol group, protection of the resulting carboxylic acid, regioselective opening of the epoxide with azide, benzoylation, and reduction, a suitably substituted moiety (28) was available which, after protection and deprotection of the acid function to form 30, was coupled to baccatin III. 

As illustrated, the major steps in the conversion of 140 to 139 correspond to non-isohypsic transformations of functional groups the reduction of an aldehyde to a primary alcohol, the oxidation of a secondary alcohol to a ketone, and the oxidation of a primary alcohol to a carboxylic acid. The introduction and removal of the isopropylidene protecting groups and the use of the bacterium Aeetobacter suboxydans (a non-typical oxidizing agent) ensures selectivity in the reactions of the polyfunctional intermediate compounds. 

According to the bioassay carried out on S. aureus Smith, the reduction of the carboxyl group brought about a decrease in antimicrobial activity, e.g. the MIC values are 3-6/u,g/ml for (77al-a3) vs. 0.031 /xg/ml for ampicillin. The azide derivative (78a) proved to be effective only against S. aureus 209 (12 /xg/ml) [135], whereas (78c and d) were ineffective in vitro. In vivo, (78b) in a dose as high as 50 mg/kg was able to protect mouse infected with S. aureus Smith when administered subcutaneously, but was ineffective orally. 

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