4- butyric acid synthesis steps

These compounds yield, on hydrolysis, the free acids, which, like all acids containing two carbo.xyl groups attached to the same carbon atom, lose COj on heating. Thus, ethyl malonic acid yields butyric acid. In this way the synthesis of monobasic acids may be readily effected. Malonic ester, moreover, may be used in the preparation of cyclic compounds as well as of tetrabasic and also dibasic acids of the malonic acid series ( Perkin). To give one illustration malonic ester, and ethylene bromide in presence of sodium alcoholate, yield triniethyleiic dicarbo.xylic ester and tetramethylene tetracarbo.xylic ester. The first reaction takes place in two steps,... 

The initial step in the metabolism of short-chain fatty acids, w hether In cells of the gut lining or in the liver, is conversion to the coenzyine A derivative. For example, acetate is converted to acetyl coeuzyme A (acetyl CoA). The acetyl Co A formed in the cytoplasm can be used for the synthesis of fatly acids, w hereas that formed In the mitochondria can be used for immediate oxidation. Propioriyl CoA can be metabolized as shown in Figure8.7 in Chapter 8. Butyric acid can enter the mitochondria for conversion to butyryl CoA and oxidation in the pathway of fatty acid oxidation. 

An attractive feature of this two-step one-pot reaction is that it not only incorporates an innovative technique for site-isolation but also produces enantiomerically enriched useful intermediates. Indeed the Michael adducts that are produced represent precursors to y-amino acids, allowing access to y-amino butyric acid analogues. Pregabalin (145) is one such analogue that is approved for the treatment of both epilepsy and neuropathic pain. Following this one-pot synthetic strategy there is no need for nitroalkene isolation and byproduct formation can be avoided. Scheme 3.42 depicts the total synthesis of pregabalin. 

After the basic mechanism of fatty acid oxidation was established, it was generally assumed that fatty acid synthesis would occur by a reversal of the oxidative pathway, except of course for those steps concerned with the transfer of electrons to molecular oxygen. This assumption was readily verified in the case of C. kluyveri where the synthesis of butyrate occurs by reversal of those steps shown in Fig. 1. However, subsequent studies in the laboratories of Wakil, Lynen, Brady and Vagelos demonstrated that the synthesis of long-chain fatty acids occurs by a different mechanism in which malonyl-CoA rather... 

A quite different approach to the pyrrolizidine nucleus starting with pyrrolidine has led to a synthesis of the alkaloids isoretronecanol (19) and trachelanthamidine (20) (Scheme 52). A novel synthesis of A -dehydropyrrolizidinium perchlorate from a-butyrolactone has been reported. The key step is the synthesis of the 2-pyrroline (21) from the butyric acid derivative (Scheme 53). 

FIGURE 7.1 Chemical synthesis of butyric acid using different precursors as a starting material using one step and a high yield. 

FIGURE 7.2 Chemical synthesis of butyric acid to butanol using different one-step synthetic routes. 

Ishii s synthetic sequence could not initially be applied to the synthesis of phenolic benzo[c]phenanthridines such as fagaronine (3), because the steps involving the hydrogenolysis of the y-oxobutyric acids to the butyric... 

The preparation of butyric-4-C acid (50% yield) involves a two-step synthesis starting viuth glutamic-l,2-C acid (Mosbach et at., 195i). The procedure requires a deamination to succinaldehydic acid which is followed by a modified Wolff-Kishner reduction. In the first step the doubly labeled glutamic acid loses one labeled C moiety to become a singly labeled aldehyde. The unstable intermediary succinaldehydic acid is prepared as needed. Coon and Abrahamsen (1952) and Zabin and Bloch (1951) prepared butyric-3-C add from ethyl-l-G iodide in yields of 41 and 51%, respectively. 

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