Acetone cholesterol synthesis

As shown in Figure 26-9, the first product, acetoacetyl-CoA, condenses in the mitochondria with a third molecule of acetyl-CoA to yield HMG-CoA. This pool of HMG-CoA is distinct from that in the cytosol that is an intermediate in cholesterol synthesis. The HMG-CoA produced in the mitochondria is then cleaved enzymatically to yield acetoacetate and acetyl-CoA. Some of the acetoacetate formed in liver cells is usually reduced to p-hydroxybutyrate. Because acetoacetate is unstable, a further portion decomposes to form carbon dioxide and acetone, the third ketone body found in... 

Another pathway of cholesterol synthesis must be considered. Triterpenoid compounds bear a formal resemblance to steroids and, indeed, acetate and acetone have been found to stimulate rubber production in guayule leaves. The following reactions (Fig. 5) are hypothesized in the... 

Another appHcation of 4-chlorophenol is in the synthesis of a dmg, ethyl a, a-dimethyl-4-chlorophenoxy acetate [637-07-0] (60), used as a cholesterol-reducing agent. This synthesis involves reaction with acetone and chloroform, followed by ethanol esterification. 

The resolution of racemic FTC butyrate (34) was required for the synthesis of the antiviral drug emtricitabine (Emtriva) (Scheme 7.15) a nucleoside reverse transcriptase inhibitor targeted for treatment of human immunodeficiency virus (HIV) and hepatitis infections [35]. The racemic FTC butyrate ester (34) was treated with immobilized cholesterol esterase, which cleaved the required isomer to the corresponding alcohol (-) 35 with 91% and 52% conversion [36]. The product was isolated as the hydrochloride salt to give 31% yield (98% ) from the 8 kg demonstration. The esterase was immobilized by precipitation onto an accurel polypropylene support using acetone followed by cross linking with glutaralde-... 

In addition to restoring the clinical appearance of xerotic skin, lanolin can also accelerate the restoration of normal barrier function to normal skin that has been acutely perturbed. Elias and colleagues have demonstrated that lanolin accelerated epidermal barrier recovery following perturbation with acetone.41 Three percent lanolin not only significantly (p < 0.001) decreased the TEWL at 45 min, but also after 4 h compared to vehicle-treated sites (Table 25.1). However, the rate of barrier recovery of lanolin-treated sites between 45 min and 4 h was not significantly different compared to vehicle treatment. This indicates that lanolin has an immediate effect on restoring a permeability barrier and does not interfere with the process of lamellar body extrusion and lipid synthesis, which are required for continued recovery. The effect of 3% lanolin on barrier recovery was very similar to that of the optimized ratio of stratum corneum lipids (ceramides, cholesterol, and fatty acids).42,43... 

The stereoisomeric mixture of -hydroxyalkyl selenides resulting from the reaction of the a-selenoalkyllithium and the carbonyl compound has been often cleanly and easily separated into its constituents by liquid chromatography on silica gel (Schemes 124,133,134, and 170 172).200.206.222,226,229,258 59 jj,jg has, therefore, allowed the synthesis of each of the two stereoisomers of various di- and tri-substituted alkenes (Schemes 124,170 and 171 Scheme 172, a) and epoxides (Scheme 124 Scheme 172, b), which are otherwise obtained as intractable mixtures of stereoisomers through the conventional phosphorus or sulfur ylide methods. Last but not least, 2-lithio-2-methylselenopropane can be used as the precursor of various compounds bearing gem dimethyl substituted carbons, such as squalene, oxido-squalene, lanosterol and cholesterol. Use of commercially available perdeuterated or Ci or — 2 acetone allows the straightforward synthesis of the corresponding labelled compounds... 

HMG-CoA is also synthesized in mitochondria by the same sequence of reactions but yields the ketone bodies acetoacetate, D(—)- 8-hydroxybutyrate, and acetone (Figure 19-10). Mitochondrial HMG-CoA also arises from oxidation of leucine (Chapter 17), which is keto-genic. Although HMG-CoA derived from leucine is not utilized in mevalonate synthesis, the carbon of leucine can be incorporated into cholesterol by way of acetyl-CoA. Thus, two distinct pools of HMG-CoA exist one... 

---