Aldol condensations biological

Having identified the (+)-stereoisomer as the biologically active isomer, several independent enantioselective syntheses of this stereoisomer were developed. The initial synthesis developed in discovery chemistry employed the diastereoselective aldol condensation pioneered by Braun as the key component. Thus, treatment of aldehyde 13 from the racemic synthesis with the magnesium enolate of (5)-(+)-2-acetoxy-l,l,2-triphenylethanol at -70 °C, afforded 17 in 60% yield as a 97 3 mixture of the / ,5 5,5-diastereomers by HPLC (Scheme 3). Ester exchange employing sodium methoxide provided the methyl ester in quantitative yield. Reaction of this ester with three equivalents of lithio-f-butylacetate at -40 °C afforded the nearly enantiomerically pure r-butyl ester analog of racemic 14 in 75% yield. 

A stereocontrolled synthesis of the biologically active neolignan (+)-dehydrodiconiferyl alcohol, which was isolated from several Taxus species, was achieved via Evans asymmetric aldol condensation [58] using ferulic acid amide derived from D-phenylalanine. The reaction steps are shown in Fig. 9. This stereocontrolled reaction is also useful for preparing the enantiomer of (+)-dehydroconiferyl alcohol using chiral auxiliary oxazolidinone prepared from L-phenylalanine. This reaction also enables the syntheses of other natural products that possess the same phenylcoumaran framework. 

The simplest explanation of this result is that the chemical reaction has followed essentially the same course as the biological one. First, the hemiacetal is opened by the base to give the open-chain keto-aldehyde. Rotation about a C-C bond allows a simple aldol condensation between the enolate of the ketone as nucleophile and the aldehyde as electrophile. 

The interest in the mechanisms of SchifF base hydrolysis stems largely from the fact that the formation and decomposition of SchifF base linkages play an important role in a variety of enzymatic reactions, for example, carbonyl transfers involving pyridoxal phosphate, aldol condensations, /3-decarboxylations and transaminations. The mechanisms for the formation and hydrolysis of biologically important SchifF bases, and imine intermediates, have been discussed by Bruice and Benkovic (1966) and by Jencks (1969). As the consequence of a number of studies (Jencks, 1959 Cordes and Jencks, 1962, 1963 Reeves, 1962 Koehler et al., 1964), the mechanisms for the hydrolysis of comparatively simple SchifF bases are reasonably well understood. From the results of a comprehensive kinetic investigation, the mechanisms for the hydrolysis of m- and p-substituted benzylidine-l,l-dimethylethylamines in the entire pH range (see, for example, the open circles in Fig. 13) have been discussed in terms of equations (23-26) (Cordes and Jencks, 1963) ... 

Examples include acetal hydrolysis, base-catalyzed aldol condensation, olefin hydroformylation catalyzed by phosphine-substituted cobalt hydrocarbonyls, phosphate transfer in biological systems, enzymatic transamination, adiponitrile synthesis via hydrocyanation, olefin hydrogenation with Wilkinson s catalyst, and osmium tetroxide-catalyzed asymmetric dihydroxylation of olefins. 

The /3-hydroxy aldehydes and -hydroxy ketones formed in aldol reactions x U P can be easily dehydrated to yield conjugated enones. In fact, it s this loss of Biological water that gives the aldol condensation its name, since water condenses out Connection of the reaction when the enone product forms. 

The biological activity of the diterpenoids of the aphidicolin-stemodin series makes these compounds attractive targets. The total synthesis of stemodin (96) has been described.172 The key spiro-centre at C-9 was constructed by the internal aldol condensation of the keto-aldehyde (97) to afford (98). Several stereoselective syntheses of aphidicolin have been reported with different solutions to the problem... 

Claisen and aldol condensation are important in biological systems, with protein catalysts that enable reactions to lake place in aqueous solution at temperatures close to ambient. 

CoA and oxaloacetate. Actually, this is another biological example of an aldol condensation reaction. It is catalyzed by the enzyme citrate synthase. The product that is formed is citrate ... 

The unique structures and important biological activities of the streptovaricins have attracted considerable attention of synthetic chemists. There are several synthetic approaches to the streptovaricin ansa chains and also to the naphthoquinone nucleus. Several building blocks for the synthesis of the ansa chain of streptovaricin A (105) have been prepared by aldol condensations, [194] by ring-opening of epoxides [195] and by the strategy termed pyranosic homologation [196]. 

The treatment of saturated enolisable aldehydes and ketones with acids is known to result in aldol condensation [1]. In the case of arylethanoid derivatives, this treatment results concomitantly in aldol condensation followed by cyclisation and aromatisation. Furthermore, when the acid used is known to promote the demethylation of methoxyphenyl derivatives into phenols, this reaction appears to lead to a great structural diversity of biologically active natural and synthetic polyphenols. In this review, I will focus on the reaction of arylpropanoid and arylethanoid derivatives with acids, mainly boron tribromide but also simple protic acids. The former allows, in a one-pot procedure, aldol condensation, cyclisation, aromatisation and demethylation. The latter may be used... 

Neopentyl glycol and isobutanol are separated by distillation. Some of the recovered isobutanol is used to extract the aqueous phase formed in the aldol condensation, and the remainder is used to produce synthesis gas. The isobutanol extract contains hydroxypivalaldehyde and starting materials. It is therefore recycled to the aldol condensation reactor. The isobutanol transferred into reactor 1 then enters reactor 2 via the organic phase. This leads to an increase in the amount of isohutanol so that, after separation by distillation, some of the isobutanol can be used to produce synthesis gas. Wastewater from the bottom of the extraction column is fractionated. The low-boiling compounds formed as overhead products are also used to produce synthesis gas (Fig. 25). Wastewater from the fractionating column is treated in the biological waste-water treatment plant. 

Enolate ion formation allows coenzyme A-bound acyl groups to serve as nucleophiles and to react at electrophilic centres. This permits thioesters to participate in the formation or degradation of carbon—carbon linkages by mechanisms analogous to the aldol condensation or more specifically the Qaisen type ester condensation. There are few available mechanisms for carbon—carbon bond formation or deavage which can be employed under biological reaction conditions, and pathways which depend on coenzyme A thioesters for this purpose are widespread. 

Kendrew SG, Deutsch E, Madduri K, Hurchinson CR. Aklanoic acid methyl ester cyclase An intramolecular aldol condensation in the biosynthesis of daunorubicin. Bloomington, Indiana Abstracts, Sixth Conference on the Genetics and Molecular Biology of Industrial Microorganisms, 1996 P4. 

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