Lengthening reaction

Due to an interest in studying their unusual reactivity (vide infra), several attempts were made to maximize yields of the strained dimers 74. Lengthening reaction times and decreasing substrate concentrations in the cyclooligomerization experiments proved fruitless. In response to this situation, a stepwise synthesis of the tetrahexyl-substituted dimer was developed as shown in Scheme 18. Surprisingly, Hay coupling of 77 resulted in an improved yield of the tetramer (45 vs 8 %) and a substantial decrease in the yield of dimer (13 vs 30%). This product distribution was unexpected, since intramolecular reactions are typically much faster than intermolecular reactions. 

In this section, the subject is subdivided into three parts. These are, first, chain lengthening reactions, second, cyclizations and last, ring expansion processes. These processes may be either chain or nonchain reactions. However, in this review, only the more common chain reactions will be discussed. The reader is referred to the reviews of Curran665 667,669 for details about the less common nonchain processes, and to the chapter by J. Green concerning metal-mediated reactions of halides in the present volume. 

Palladium on barium sulfate, Pd/BaS04 Acts as a hydrogenation catalyst for nitriles in the Kiliani-Fischer chain-lengthening reaction of carbohydrates (Section 25.6). 

More recently, the use of high pressure with tetra-n-butylammonium fluoride as catalyst allowed these reactions to be accomplished with cyclic ketones. Thus, the Henry reaction of nitroalkanes with 3- and 4-methylcyclohexanones in THF at 30 C and 9 kbar (1 bar = 100 kPa) afforded fair to high yields (60-90% after 4 d) of the corresponding nitro alcohols, while with 2-methyIcyclohexanones it was possible to obtain addition products, although in moderate yields. These facts explain the modest utility of the Henry reaction as a chain-lengthening reaction when the carbonyl component is a ketone, but also show the difference in reactivity of aldehyde and ketone C==0 groups with respect to nitromethane, primary and secondary nitroalkanes in the presence of a base as catalyst. Such a difference in reactivity can be considered as the most evident chemoselectivity of this reaction. 

Several additional reactions are required for the elongation of fatty-acid chains and the introduction of double bonds. When mammals produce fatty acids with longer chains than that of pahnitate, the reaction does not involve cytosolic fatty-acid synthase. There are two sites for the chain-lengthening reactions the endoplasmic reticulum (ER) and the mitochondrion. In the chain-lengthening reactions in the mitochondrion, the intermediates are of the acyl-GoA type rather than the acyl-AGP type. In other words, the chainlengthening reactions in the mitochondrion are the reverse of the catabolic reactions of fatty acids, with acetyl-GoA as the source of added carbon atoms this is a difference between the main pathway of fatty-acid biosynthesis and these modification reactions. In the ER, the source of additional carbon atoms... 

FIGURE 21.18 A portion of an animal cell, showing the sites of various aspects of fatty-acid metabolism. The cytosol is the site of fatty-acid anabolism. It is also the site of formation of acyl-CoA, which is transported to the mitochondrion for catabolism by the P-oxidation process. Some chainlengthening reactions (beyond Cjg) take place in the mitochondria. Other chain-lengthening reactions take place in the endoplasmic reticulum (ER), as do reactions that introduce double bonds. 

The utility of this methodology is illustrated by the stereoselective synthesis of ( + )-cer-ulenin (759), an antifungal antibiotic first isolated from the culture filtrate of Cephalosporium caerulens. Its ability to inhibit lipid biosynthesis in Escherichia coli by irreversibly binding P-keto-acyl-carrier protein synthetase, the enzyme responsible for the chain lengthening reaction in fatty acid synthesis, has attracted interest in its mechanism of action. D-Tartaric acid... 

Workers who used methylene chloride in making acetate film had sleepiness and fatigue and decreased digit symbol substitution scores and lengthened reaction time. Use of methylene chloride in closed spaces has been fatal with brain edema, elevated blood levels of carboxyhemoglobin and caused temporary right hemispheric paralysis and/or unconsciousness. Chronic exposure has been associated with dementia, headache, dizziness and disturbed gait. ... 

The over all chain-lengthening reaction can be shown in a single step (see Eq. 3.3). 

Chain-lengthening reactions can be applied to carbohydrates. As the term implies, the carbohydrate chain is extended by one carbon. One important method uses a transformation called the Nef reaction, after John U. Nef (Switzerland/ United States 1862-1915). When d-threose (13) reacts with nitromethane in the presence of sodium methoxide as a base, the enolate anion of nitromethane (90) reacts with the aldehyde unit of 13 (an enolate-aldehyde condensation reaction see Chapter 22, Section 22.2, for related reactions) to give two products 91 and 92. 

When, however, the chain-lengthening reactions with the pure Cj5 aldehyde isomers (349) and (350) were carried out using methyl 4-diethylphosphono-senecioate ( /Z = 1.3), conventional secondary reactions gave mixtures of the aldehydes (354) and (356) and of the aldehydes (355) and (356), and these mixtures were separated by chromatography (Asato and Liu, 1975 Ramamurthy and Liu, 1975 Ramamurthy et aL, 1975 Liu and Asato, 1982). ... 

Following activation of dopaminergic transmission after systemic injection ofd-amphetamine or intrastriatal injection of dopamine the rats showed premature responses and shortened reaction times. In contrast, blocking D2 receptors with raclopride the rats showed delayed responses and lengthened reaction times. 

Hienz et aL (1997) found cocaine reducing the reaction times in two baboons and not affecting it in one baboon whereas quinpirole, a relatively selective D2/D3 dopamine agonist, lengthened reaction time in a dose dependend manner. 

What is the junction between striatal dopamine and reaction time Either the striatum plays a role in the RT pathway or changing the striatal dopamine elicits a compensating reaction in the cortex dopamine. With this hypothesis the contradictions of dopamine effect do not exist any more subcortical dopamine depletion and cortical dopamine activation leads to lengthened reaction times, subcortical dopamine activation and cortical dopamine depletion causes prolonged reaction times. 

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