Functional groups hydroxyl/hydroxy

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

A number of ketones, pharmaceutical compounds, alcohols and hydroxy acids have also been resolved on this phase [724,765-767]. A chiral polysiloxane phase with tartramide substituents has been used for the separation of enantiomers capable of hydrogen bonding interactions with the stationary phase, such as enantiomers containing carboxylic, hydroxyl and amine functional groups [768]. 

Another chemically more interesting spin labeled B12 derivative involves coordinate attachment of the nitroxyl function to the cobalt atom of a cobinamide. Fig. 22 shows a reaction in which an alkyl cobin-amide is mixed with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. The nitroxide displaces water from the 6th coordination position very slowly and therefore this reaction is usually allowed to proceed for a few days with a large excess of nitroxide. From the properties of the coordinated nitroxide derivative discussed below, it is certain that the cobalt is coordinated by the N—O functional group. An analogous compound to that shown in Fig. 22 can be made with a similar nitroxide in which the 4-hydroxyl-group is missing. In this case the N—O-function is the only basic site on the molecule and therefore must be the position of attachment to the cobalt 119). 

Several assumptions were made in order to analyze kinetic data in terms of this expression (2). First it was assumed that k 2 m kj, k2 k 3, and kj/k j k /k ( - If). Second it was assumed that the rate constants were independent of the extent of reaction i.e., that all six functional groups were equally reactive and that the reaction was not diffusion controlled. The concentration of polymer hydroxyl functionality was determined experimentally using infrared spectroscopy as described elsewhere (7). A major unknown is the instantaneous concentration of methanol. Fits to the kinetic data were made with a variety of assumptions concerning the methanol concentration. The best fit was achieved by assuming that the concentration of methanol was initally constant but decreased at a rate proportional to the concentration of residual polymer hydroxy groups towards the end of the reaction. As... 

An alpha hydroxy acid is an organic carboxylic acid in which an additional hydroxyl functional group (-OH) is present at the alpha position, i.e., on the carbon adjacent to the carboxyl functionality, -COOH. Figure 13.10.1 presents the struc-... 

The bifunctional initiator 4-hydroxy-bulyl-2-bromoisobulyralc, HBBIB, promoted the ATRP of styrene as well as the cationic ring opening polymerization of THF [134], In the presence of Cu/CuBr2/PMDETA styrene was polymerized through the bromoisobutyrate function of HBBIB, to give PS chains end-functionalized with hydroxyl groups, PS-OH. The in situ... 

Acetyltransferases catalyze the acetylation of amino, hydroxyl, and thiol functional groups. Acetylation of hydroxy and thiol groups is comparatively rare and of much less importance in alkaloid metabolism than reactions with amino functional groups. The types of amines that are acetylated include arylamines (the major route of metabolism in many species), aliphatic amines, hydrazines, sulfonamides, and the a-amino group of cysteine conjugates. The purification, physical properties, and specificity of the N-acetyltransfereases have been reviewed (116-118). 

Allylic alcohols are interesting substrates for epoxidation because they produce epoxides with a hydroxyl group as additional functional group that is able to play an important role in the subsequent synthesis of complex molecules [105]. This synthesis aspect certainly benefits from the hydroxy-group directed selectivity of oxygen delivery. 

Therefore, the chiral cyanohydrins are valuable and versatile synthons as their single hydroxyl asymmetric centre is accompanied by at least one other chemical functionality. Thus with careful functional group protection, differential and selective chemical transformations can be performed. Such synthetic techniques lead to production of interesting bioactive compounds and natural products. These products include intermediates of j3-blockers 15 1117], j3-hydroxy-a-amino acids 16 [118],chiral crown ethers 17 [lll],coriolic acid 18 [120], sphingosines 19 [121], and bronchodilators such as salbutamol 20 [122] (Fig. 3). 

Derivatization of functional groups in a natural-product scaffold can also be effectively performed on the solid-phase. An example of this is the synthesis of a small compound collection (27-compounds) based on the tetrahydroquinoline scaffold. A chiral tetrahydroquinoline scaffold was synthesized in solution from 5-hydroxy-2-nitrobenzaldehyde (Scheme 4). The synthesis involved a key asymmetric aminohydroxylation step. This building block was anchored to the solid support with a Wang linker and diversity was introduced by selective deprotection and derivatization of the protected hydroxyl and amino substituents. 

The Fischer indole synthesis is quite tolerant of additional functional groups in the starting material. Thus reaction of 4-dimethylaminocyclohexanone (18-2) with phe-nylhydrazine (18-1) in acetic acid leads directly to cyclindole (18-3) [18], a compound described as an antidepressant. A shghtly different approach is used to prepare the fluorinated analogue. The tricyhc indole (18-5), in this case, is obtained by reaction of 2,4-diiluorophenylhydrazine (18-4) with 4-hydroxy-cyclohexanone. The hydroxyl... 

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