Side-chains, in steroids

Ti complexes have been extensively used for the stereoselective introduction of side chains in steroidal molecules, e.g. pregnenolone acetate and the steroidal C-22 aldehyde (73 equation 29). In these cases satisfactory results are only obtained by using Ti reagents, like methyl, ds-methyl and allyl derivatives, due to the strong steric hindrance that affects the position to be attacked. 1,3-Anti dia-stereoselecdon in the addition of alkyltitanium reagents to chirally -substituted aldehydes having a dithioacetal group at the a-position (75) was also observed (equation 30). ... 

Other stmctural variations in both series are the stereochemistry at C3 and the degree of oxidation on the nucleus and side chains. Cardiac steroids probably exert their inotropic effects by acting as specific, noncompetitive inhibitors of — ATPases, known as sodium pumps, and thus... 

B. Characteristic Fragment Ions The most characteristic cleavage is the loss of carbons 15,16, and 17, together with the side chain and one additional hydrogen. It is possible to determine the elemental composition of the side chains of steroids by the difference in the mass between the molecular ion and an intense ion more than 15... 

Bjorkemd, I., 1992, Mechanism of degradation ofthe steroid side chain in the formation of bile acids, 7. Lipid Res. 33 455-471. 

Oliveto EP (1972) Synthesis and degradation of the pregnane side-chain. In Fried J, Edwards JA (eds) Organic reactions in steroid chemistry, vol 2. Van Nostrand Reinhold, New York, p 127... 

Stereocontrolled functionalization of steroidal side chains in nature is closely related to the function of steroids in living organisms. The regio- and stereochemistry of functional groups exert strong influence on the biological activities of steroids. Due to their multi-functional nature, the homoenolates provide an effective tool for synthetic efforts in this field. 

A further example is the ready assignment of an olefinic resonance which appears in the spectrum of ruberoside G in addition to the H-ll signal at 5.3 ppm, common to asterosaponins. Its low-field chemical shift of 6.2 ppm (solid frame in Figure 5.1.4, and Figure 5.1.5) indicates the presence of a double bond in the steroidal side-chain in proximity to a deshielding functional group such as a carbonyl. 

Several sulfated polyhydroxysterols have been recently isolated from sponges. Most of these natural products are characterized by the 2p,3a,6a-tri-0-sulfate functions together with additional alkylation in the side chain. These steroids are of interest not only because of their structures but... 

Using this reaction, the steroidal alkynyl side chain in 419 is extended with allylic alcohol to afford 420 with the Ru complex without phosphine [164], However,... 

Generally speaking the classical alkaline hydrolysis reaction followed by back-titration could be used to determine steroid esters. The results for 21-acyloxycortico-steroids (where R = H, OH) are however quite unsatisfactory. The reason behind the unacceptable result is the auto-oxidation of the a-ketol side-chain in an alkaline medium. Because of the formation of acidic products in side reactions, there is an over consumption of base in the titration and a corresponding over determination of the amount of steroid. 

Schouten S., Sephton S., Baas M., and Sinninghe Damste J. S. (1998b) Steroid carbon skeletons with unusually branched C-3 alkyl side chains in sulphur-rich sediments. Geochim. Cosmochim. Acta 62, 1127-1132. 

This disease is caused by an autosomal recessive gene mutation (localization on chromosome 2) and leads to an enzyme defect in mitochondrial steroid-27 hydroxylase. The enzyme itself is responsible for the breakdown of cholesterol side-chains in bile acid synthesis. Such a defect results in the formation of cholestanol, a reduction product of cholesterol. It is deposited in various organs, particularly in the tendons and in the nervous system, because the substance cannot be broken down adequately. Deposition takes place conjointly with cholesterol. (209, 210)... 

Examples are found for the selective hydroxylation, dehydrogenation and oxidative removal of side chains of steroids, and for the selective oxidation of sorbitol into L-sorbose in the vitamin C synthesis. 

A. The enzyme sterol 27-hydroxylase catalyzes the hydroxylation of carbon 27 of the steroid side chain in the conversion of cholesterol to the primary bile acids. It is a mitochondrial, cytochrome P450 enzyme that has a broad specificity and can act on cholesterol as well as its reduced and hydroxylated metabolites. A deficiency in this enzyme leads to decreased bile acid synthesis and increased conversion of cholesterol to cholestanol. 

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