Hydroxymethyl ketones carboxylic acids

Metallation of TTF (5) has been accomplished at — 78°C by either lithium diisopropylamide or by -butyllithium (Scheme 82) <77CC161,79JOC1476>. It has been found that strict temperature control is essential for the success of these reactions, since at — 20°C a redistribution of product formation is observed <79J0C1476>. 1-Lithio-TTF (426) reacts at —70°C with a series of electrophiles to afford the corresponding alcohols, aldehydes, ketones, carboxylic acids, and esters as well as monoalkylated TTF <77CCi6i, 79JOCi476>. Improvement of this procedure allowed the synthesis of carboxy-TTF (427), formyl-TTF (428), and hydroxymethyl-TTF in 80-92% yield (Scheme 83) <94S489>. 

Substitution can vary at the R position. A variety of R groups, including a carboxylic acid, a hydroxymethyl group, a ketone, or a benzimidazole ring, are present in currently available ARBs and are thought to interact with the AT 1 receptor through either ionic, ion-dipole, or dipole-dipole bonds. 

Selective oxidative degradation Carboxylic acids from hydroxymethyl ketones... 

The transformation of acid chlorides into hydroxymethyl ketones can be achieved in good yield under mild conditions using tris(trimethylsilyloxy)ethylene. a-Hydroxy-carboxylic acids, readily available from carboxylic acids, are decar-bonylated at room temperature on treatment with a benzoxazolium salt and triethylamine to give ketones in good yields [equation (7)]. ... 

C,3R,5- H2]mevalonic acid is [3Hi while lophenol is [ Hn, " 5]. It must be concluded that, contrary to earlier reports, the 4a-methyl group is lost first. This result is further substantiated by the incorporation of 4a-hydroxy-methyl-4j3-methylcholestan-3j8-ol but not the 4jff-hydroxymethyl isomer. Furthermore, 4j9-methylcholestan-3)S-ol is largely inert. The sequence of events would seem to be that the 4a-methyl is oxidised to a carboxyl group and the 3)3-hydroxyl to a 3-ketone. Decarboxylation of the jS-keto acid is followed by rapid reduction of the 3-ketone back to a 3/9-alcohol. In the presence of tritiated water C-3 and C-4 become radioactive. ... 

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