Functional group activation carboxylic acids

Reaction of the side chain hydroxyacetone in flumethasone (27-4) with periodic acid leads to cleavage of that function to give carboxylic acid (29-1) with the loss of the carbon atom at C-21. Further reaction of the very hindered acid group requires prior activation. Thus, acylation with diphenyl chlorophosphate leads to the mixed anhydride (29-2) this is not isolated, but treated immediately with methyl mercaptan. The product, tibecasone (29-3), is a quite effective topical anti-inflammatory agent [24]. Cleavage of the ester side chain would lead back to the inactive starting acid (29-1). 

A cursory glance at the structure of DNA shows that it is composed of hydrogen-bonded units, the purine and pyrimidine bases, attached to sugars that are linked by phosphate groups. There is no chemical reason why the perfectly symmetric phosphates should bind in the orientation that they do. The same problem arises in when a synthetic analogue of a DNA-type replicator is considered. The most useful linkages are imine and peptide bonds. Both require a terminal amine the former results from a reaction with an aldehyde and the latter with an activated carboxylic acid. The problem that occurs is that if these functional groups are present within the same molecule self-polymerization may occur unless a substantial effort is made to avoid this. 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

Hypericin 1 is very poorly soluble in many solvents. In view of its potent antiviral activity especially against HIV this is a major drawback as it restricts the bioavailability of this compound. Researchers have tried many ways to find better soluble forms of hypericin 1 in both water and organic sovents e.g. by preparing esters, ethers, salts, amino acid complexes [26] or by preparation of ion pairs [27]. Other possibilities of solubility improvement included the introduction of polar functions such as carboxylic acid groups [28]. 

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