Carbon aldonolactones

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

New Aldonolactones by Stereoselective Isomerization at One or More Carbon Atoms... 

So far only a table of the 13C chemical shifts of aldonic acid salts and aldonolactones has been published in the literature (Table 5.20, [696]). The carbons of the carboxylate ion groups of all D-aldonic acid salts resonate at 180 + 0.7 ppm. Upon /-lactone formation an upfield shift for C-l and a downfield shift for the /-carbon is observed throughout. 

We thus investigated a range of such one-carbon electrophiles (Scheme 10). Formaldehyd, as the most reactive one, gave the desired product directly (28). Using benzaldehyde as the electrophile likewise lead to a C-2 branched aldonolactone in a high yield and stereospecificity. The two diastereoisomeric compounds obtained, due to the new chiral center formed in the side chain, were both isolated in a crystalline state (28). 

When the bromodeoxy lactones were boiled in water tetrahydrofurans were formed, whereas catalytic hydrogenation caused deoxygenation at C-2 and/or at the primary position, while the acetylated aldonolactones could also be reduced to 3-deoxylactones after elimination and stereospecific reduction. Substitution by azide introduced nitrogen functions at C-2 or at both bromo-substituted carbons, and these compounds could be converted into the corresponding amino acids. The new molecules could furthermore be reduced to the corresponding aldoses or alditols. 

In 1885, Heinrich Kiliani (Freiburg, Germany) discovered that an aldose can be converted to the epimeric aldonic adds having one additional carbon through the addition of hydrogen cyanide and subsequent hydrolysis of the epimeric cyanohydrins. Fischer later extended this method by showing that aldonolactones obtained from the aldonic acids can be reduced to aldoses. Today, this method for lengthening the carbon chain of an aldose is called the Kiliani-Fischer synthesis. 

Aldonolactones activated at the primary position very rapidly form a primary epoxide of the open aldonic acid when dissolved in aqueous base. Usually, 3 molar equivalents of potassium hydroxide are used to keep the pH above 14. This is a prerequisite for a Payne rearrangement and/or for opening of the epoxide by an intramolecular nucleophile. Using the weaker base potassium carbonate, no rearrangement will take place and hence the primary epoxide will be opened at the primary carbon by hydroxide. Pentonolactones activated at C-5 will isomerise stereospecifically at C-4 when treated with strong potassium hydroxide. This is due to the opening of the primary epoxide by the carboxylate... 

Stereoselective Inversion of Configuration at More Than One Carbon Atom in Aldonolactones by Payne Rearrangements... 

When o>-activated aldonolactones with six or more carbon atoms are treated with strong aqueous base, the primary epoxides of the polyhydroxy carboxylic acids first formed may rearrange to secondary epoxides, which can finally be opened at C-4 by the carboxylate in a five-membered transition state. The driving force, and thus the success of the stereoselective inversion at more carbon atoms in the polyhydroxy acids, is the final opening of an epoxide at C-4. The method has been used to prepare a number of less available aldonic adds/lac-tones, as illustrated in the following examples. 

As pointed out above, aldonolactones/adds may isomerise at C-2 in the presence of strong base. No isomerisations were detected in the reaction of the 2,3-0-isopropylidene-protected lactones 3 and 5 with strong aqueous potassium hydroxide. Likewise, unprotected 5-bromo-5-deoxy-D-lyxono- and -D-ribono-lactones give rearrangements to L-ribonic and L-lyxonic acids, respectively [19]. In these cases isomerisation at C-2 was not observed either. It has thus been confirmed that aqueous base requires higher temperatures in order to epimerise at the carbon center a to the carboxylate group. 

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