Symmetrical compounds, alcohols

The term acjdoin is commonly used as a class name for the symmetrical keto-alcohols RCOCH(OH)R, and the name of the individual compound Is derived by adding the suffix oin to the stem name of the acid to which the acyloin corresponds, e.g., acetoin, propionoin, butyroin, etc. 

Application of the bromine substitution reaction allows the synthesis of aminoamides, alkoxyamides of simple alcohols and sugars, depsipeptides and (NH) pseudopeptides, C2 symmetric compounds. 

Dyes for cellulose acetate are relatively simple molecules, typified by Cl Disperse Red 15 (6.39 X = OH), Cl Disperse Violet 4 (6.39 X = NHCH3) and Cl Disperse Blue 3 (6.40), the last-named being manufactured from leucoquinizarin and the appropriate amines. The unsymmetrically substituted product inevitably contains significant amounts of the related symmetrical compounds. The widely used Cl Disperse Blue 3 is known to cause skin sensitisation when on nylon [17] and can also provoke an allergic reaction [18]. Bright red 2-alkoxy-l-amino-4-hydroxyanthraquinones, such as Cl Disperse Red 4 (6.41), can be obtained from l-amino-2,4-dibromoanthraquinone by hydrolysis to give l-amino-2-bromo-4-hydroxyanthraquinone (Cl Disperse Violet 17), which is then condensed with the appropriate alcohol. 

It will be noted that the symmetrical compound carbon tetrachloride differs markedly in the ratio from the unsymmetrical methyl alcohol. 

Both (31)(Fig. 10.9b) and (32) (Fig. 10.11) bind to the HIV-P active site asymmetrically. However, after the X-ray studies of crystalline HIV-P apoenzyme revealed it to be a symmetrical dimer, C2 symmetric inhibitors were designed to take advantage of this structural feature (Fig. 10.12). Both alcohol diamines and diol diamines were examined. For example, the C2 symmetric compound (33) (A-77003) was synthesized at Abbott and entered clinical trials as an antiviral agent for intravenous treatment of AIDS (100). 

When X and Y are polar functions, they are made essentially from functional groups such as alcohols, amines, acids, amides, amidines, or guanidines (Figure 14.4). A classical representative of a difunctionalized, symmetrical compound is decamethonium. 

By protecting sensitive functional groups like ketones it becomes possible to make reagents that would otherwise be unstable. In a synthesis of the natural product porantherine, a compound based on the structure in the margin was needed. As it s a symmetrical secondary alcohol (see p. 216), a good way to make it is to add a Grignard reagent twice to ethyl formate. 

Carbohydrates and their derivatives. There are a great many simple carbohydrates available, but one of the most useful is mannose. Reduction to the alcohol gives the C2-symmetric compound mannitol, which can be converted to a useful aldehyde by selective protection as a bis-acetal with acetone and a Lewis acid. Cleavage of the remaining diol with sodium periodate gives two equivalents of a useful protected form of glyceraldehyde. 

As a symmetrical ketone, acetone is a reactive compound with many synthetic uses. Among the important chemicals based on acetone are methylisobutyl ketone, methyl methacrylate, ketene, and diacetone alcohol. 

The tvans alcohol (47) might be made by reduction of ketone (48). Oxidation of (45) would give (48), but an alternative is to add an activating group and disconnect as a 1,3-dicarbonyl compound - standard strategy ior a symmetrical ketone. 

Stockman and coworkers [329] developed a straightforward synthesis of a tricyclic compound 2-636 which has some resemblance to the spirocyclic portion of the natural product halichlorine (2-637) [330]. On treatment of the symmetrical ketone 2-633, accessible in five steps from alcohol 2-632, with hydroxylamine hydrochloride the spiro piperidine 2-636 could be obtained in 62% yield (Scheme... 

A systematic investigation of the free amino acids of the Leguminosae led to the isolation of a novel ninhydrin-positive compound from the leaves of Derris elliptica Benth. (Papilionidae) (93). This substance was analyzed as C6H,3N04 (microanalysis and high resolution mass spectrometry) and was shown to be an amino alcohol. The absence of a carbonyl in the 1R, the loss of 31 mass units in the mass spectrum, and a positive periodate cleavage reaction were best embodied into a dihydroxydihydroxymethylpyrrolidine structure. The relative simplicity of the NMR spectra (three peaks in the 13C spectrum four spin-system in the H spectrum) pointed out a symmetrical structure. Inasmuch as the material was optically active ([a]D 56.4, c = 7, H20), meso structures were ruled out, and the 2R, 3R, 4R, 5R relative configuration was retained (93). This structure (53) was further confirmed by an X-ray determination (94). 

Finally, Inanaga s contribution to the development of chiral 4-dialkylaminopyrid-ine based catalysts for enantioselective acyl transfer relied on the use of C -symmetric 4-PPY derivative 36 (Fig. 7) [130]. This compound was obtained in an enantiopure form by selective cleavage of a carbamate intermediate using Sml, and allowed the KR of various. yec-alcohols with selectivity factors ranging from y = 2.1 to 14. 

Hydrogen abstraction from the two optically active compounds 16 and 19 gives rise to the formation of symmetrical radicals from which only the racemic cis- and frans-alcohols in a ratio of 1 1 were formed. On the other hand, photosensitized oxygenation of 16 and 19 resulted... 

Chain elongation during polymerization of prenyl units can be terminated in one of a number of ways. The pyrophosphate group may be hydrolyzed to a monophosphate or to a free alcohol. Alternatively, two polyprenyl compounds may join "head to head" to form a symmetric dimer. The C30 terpene squalene, the precursor to cholesterol, arises in this way from two molecules of famesyl diphosphate as does phy-toene, precursor of the Qo carotenoids, from E,E,E geranylgeranyl diphosphate. The phytanyl groups of archaebacterial lipids (p. 385) arise rather directly from geranylgeranyl diphosphate by transfer of the poly-... 

Support-bound alcohols and thiols can be used to immobilize aldehydes and ketones as acetals. Mixed acetals of carbonyl compounds with support-bound alcohols can be prepared by transacetalization of a symmetric acetal under acidic conditions [719]. The formation of mixed acetals on solid phase is, however, not always easy to perform and control, and so prior preparation of a mixed acetal in solution followed by loading onto a support is often the preferred protocol [626,637]. Carbohydrates can be linked to resin-bound alcohols or thiols as glycosides (Table 3.40). 

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