Esterification of steroids

The esterification of steroids is a step in the synthesis of modified hormones. H2PW 2O40 and 25% HjPW CWSiOz (1-9%) in CH3CN (at 313-353 K) give a quantitative yield (363). The activities of the heteropolyacids are close to that of HC104 and much greater than that of 5-sulfosalicylic acid. 

There are several naturally occurring androgens and probably thousands of synthetic androgens. Some of the more commonly used synthetic androgens are esters. Esterification of steroids bearing a hydroxyl group at the 17-position has been demonstrated to improve duration of biolo-... 

Pyridinotriazolides were used for esterification in the presence of DBU under mild conditions, and for the selective acylation of steroids. 1271... 

HDL particles extract cholesterol from peripheral membranes and, after esterification of cholesterol to a fatty acid, the cholesteryl esters are delivered to the liver (to make bile salts) or steroidogenic tissues (precursor of steroids). 

Glucocorticoids are available in a wide range of preparations, so that they can be administered parenterally, orally, topically, or by inhalation. Obviously the oral route is preferred for prolonged therapy. However, parenteral administration is required in certain circumstances. Intramuscular injection of a water-soluble ester (phosphate or succinate) formed by esterification of the C21 steroid alcohol produces peak plasma steroid levels within 1 hour. Such preparations are useful in emergencies. By contrast, acetate and tertiary butylacetate esters must be injected locally as suspensions and are slowly absorbed from the injection site, which prolongs their effectiveness to approximately 8 hours. 

Studies by Bell and coworkers have shown that DEHP also can alter sterologenesis in rodents, which may have an impact on steroid-dependent functions, such as reproductive functions. For example, feeding female rats DEHP at an estimated dose of 500 mg/kg/day for 13 days significantly inhibited sterologenesis from 14C-mevalonate in liver and adrenal minces (Bell 1980). DEHP also inhibited cholesterol synthesis in the liver from male rats and rabbits as well as in rats testes (Bell 1982). In a subsequent study, Bell and Buthala (1983) demonstrated that the inhibition of cholesterol synthesis in the liver was due to a reduction in the activity of microsomal acylCoA cholesterol acyltransferase, an enzyme responsible for the esterification of cholesterol. 

The combined action of lithium in liquid ammonia and carbon dioxide upon androst-4-en-3-one led to a synthesis of the /3-keto-ester (189), after esterification of the intermediate acid the reaction is one of reductive methoxycarbonyla-tion.82 Alkylation of the keto-ester (189) afforded a separable mixture of the 4/3-methyl steroid (190) as the major product (55%) and the corresponding 4a-methyl epimer. Reduction of the steroid (190) led to 4a-hydroxymethyl-4/3-methyl-5a-androstan-3/3-ol. Finally in this section, it has been noted that vinyl-magnesium bromide effects 1,4-addition to the a(3-unsaturated ketone 17/3-hydroxy-5a-androst-l-en-3-one to yield la-vinyl-5a-androstan-3-on-17/3-ol, which could be further reduced to the la-ethyl-3-ketone.83... 

The boronic acid binding site can also be used for interactions with monoalcohols. In the presence of an ort/zo-hydroxymethylene group (see entry 1), an intramolecular cyclic monoester is formed (boronophthalide). This compound still has one hydroxyl group left for the esterification of monoalcohols, a reaction that can be used in the imprinting procedure [46,47,72]. Recently this method has been revived for the binding of steroid alcohols [73,986,c]. 

N/Ac MeCN, or CH2C12 POM-acid catalyzed esterification and acetylization of steroids 40 °C (AmC0)20 was added as a reactant 538... 

Bertinotti, A., Carrea, G., Ottolina, G., and Riva, S., Regioselective esterification of polyhydroxylated steroids by Candida antarctica lipase B, Tetrahedron, 50, 13165-13172, 1994. 

An ester is a chain composed primarily of carbon and hydrogen atoms. This chain is typically attached to the parent steroid hormone at the 17th carbon position (beta orientation), although some compounds do carry esters at position 3 (for the purposes of this article it is not crucial to understand the exact position of the ester). Esterification of an injectable... 

Long-range substituent effects of unknown mechanism influence the esterification of 5-en-3)3-ols by racemic a-phenylbutyric anhydride. Hydrolysis of the resulting esters gave a-phenylbutyric acid with modest optical activity, the sign depending upon the nature of C-17 substitution in the steroid employed. "... 

A review of the synthesis and chemistry of nitroxide spin labels includes a number of steroid derivatives. Novel spin-labelled steroids have been prepared by esterification with the nitroxyl carboxylic acid derivative (17),for use in spin immunoassays (SIA) as an alternative to radioactive labelling. The prednisolone ester (18), for example, exhibits an e.s.r. spectrum with narrow lines when it is in a free state in solution, but when bound to antibody the rate of tumbling is reduced, and linewidths are broad. Signals from bound and unbound derivatives are easily distinguished and measured, so SIA of antibody-bound prednisolone provides a potentially useful serum assay method. 

Excess cholesterol can also be metabolized to CE. ACAT is the ER enzyme that catalyzes the esterification of cellular sterols with fatty acids. In vivo, ACAT plays an important physiological role in intestinal absorption of dietary cholesterol, in intestinal and hepatic lipoprotein assembly, in transformation of macrophages into CE laden foam cells, and in control of the cellular free cholesterol pool that serves as substrate for bile acid and steroid hormone formation. ACAT is an allosteric enzyme, thought to be regulated by an ER cholesterol pool that is in equilibrium with the pool that regulates cholesterol biosynthesis. ACAT is activated more effectively by oxysterols than by cholesterol itself, likely due to differences in their solubility. As the fatty acyl donor, ACAT prefers endogenously synthesized, monounsaturated fatty acyl-CoA. 

Protection of the oxo-group in 2a-cyano-3-oxo-steroids (420) by acetal formation (421) permits alkaline hydrolysis of the cyano-group. After esterification of the carboxylic acid (422), the 3-oxo-group could be regenerated (423). Alternatively, protection of the ketone could be achieved by forming a 3-enol ether. Other routes to esters of 2-carboxy-3-oxo-steroids and to the derived 3-alkoxy-, 3-amino-, and 3-chloro-A -unsaturated derivatives have also been devised. ... 

Esterification of the carboxylic acid decreases the number of hydrogen-bond donor group at the steroidal side chain, leading to a reduction of their inclusion... 

Since the beginning of enzyme catalysis in microemulsions in the late 1970s, several biocatalytic transformations of various hydrophilic and hydrophobic substrates have been demonstrated. Examples include reverse hydrolytic reactions such as peptide synthesis [44], synthesis of esters through esterification and transesterification reactions [42,45-48], resolution of racemic amino acids [49], oxidation and reduction of steroids and terpenes [50,51], electron-transfer reactions, [52], production of hydrogen [53], and synthesis of phenolic and aromatic amine polymers [54]. Isolated enzymes including various hydrolytic enzymes (proteases, lipases, esterases, glucosidases), oxidoreductases, as well as multienzyme systems [52], were anployed. 

Important reactions of free steroids include esterification, where esters and glycosides of steroid compounds are easily hydrolysed. These reactions in food raw materials are catalysed by sterol esterases and glycosidases, respectively. Other important reactions of steroids include elimination and substitution reactions and oxidation. Hydrogenation of steroids is of industrial importance. 

Miilunpohja, M., Uphoff, A., Somerhaiju, R, Tiitinen, A., Wahala, K. and Tikkanen, M.J., Fatty acid esterification of hpoprotein-associated estrone in human plasma and follicular fluid. J. Steroid Biochem. Mol Biol, 100, 59-66 (2006). 

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