Steroidal esters, hydrolysis

A representative of the second group is the hydrolysis of 3,5-dinitro-benzoic acid esters of hydroxysteroids. The waves of the nitro-groups in the steroid ester are significantly smaller than those of 3,5-dinitrobenzoic acid, and the hydrolysis has been followed by the increase in the wave-height with time (18). 

Kll. Kohen, F., Kim. J.-B., Barnard, G., and Lindner, H. R., Antibody-enhanced hydrolysis of steroid esters- Biochim. Biophys. Acta 629, 328-337 (1980). 

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. 

The Leukart reaction has also been used in the conversion of dehydroepiandro-sterone into 17/3-formylamino-3/3-formyloxyandrost-5-ene, which on reduction with lithium aluminium hydride afforded 3/3-hydroxy-17/3-me thylaminoandrost-5-ene. Acylation with isocaproyl chloride then furnished the N-methyl-N-isocaproyl steroid (197), after selective ester hydrolysis of the initially formed ON-diacyl derivative. The amide (197) was further converted into its 3,5-cyclo-6-ketone via the 3,5-cyclo-6/3-alcohol and thence by reaction with hydrogen bromide into the corresponding 3/3-bromo-5a-6-ketone which upon dehydrobromination furnished a A2-5a-6-ketone and ultimately the 2-monoacetate of the 2/3,3/3-diol (198) after reaction with silver acetate and iodine. Hydrolysis to the 2/3,3/3-diol (198) gave a separable mixture of the 2/3,3/8-dihydroxy-5a- and -5/3-ketones.88... 

Further consequences of the distinction between axial and equatorial bonds lie in different rates of acylation of steroid alcohols, hydrolysis of esters, and oxidation of secondary alcohols, which were among the earliest steroid reactions to be interpreted in conformational terms. These reactions are discussed in Chapter 2. 

C and A are new bases from Stephanotis steroidal esters of y-methylanthranilic on spectral evidence, is assigned structure and sterochemistry represented by (95) (S. Terada et at.. Tetrahedron Letters, 1978, 1995). The latter on total hydrolysis affords the known steroid sarcostin (96), and a careful analysis of its pmr- and C-nmr-spectra, with appropriate comparisons with model esters derived... 

Our laboratory is concerned with targeting potential insecticides that disrupt normal development and metamorphosis in insects. Juvenile hormones (JHs), acting in concert with the steroid hormone ecdysone, are believed to control the timing of the larval-larval molts, larval-pupal and pupal-adult transformations of the insects. It has been demonstrated that the events leading to pupation are initiated by reduction of the JH titer in the hemolymph. In addition to a cessation of biosynthesis, this reduction in JH titer is controlled by degradative metabolism (16,17). Hydrolysis of the epoxide and ester functionalities present in active JH are two routes of degradation and subsequent inactivation of JH (18). The primary route of JH metabolism in the hemolymph of last stadium lepidopterous larvae is ester hydrolysis, and it is catalyzed by the enzyme juvenile hormone esterase (JHE). JHE has been shown to... 

The mechanism of catalysis for hydrolysis of steroid esters to steroid alcohols has not been elucidated in particular. In view of the nonspecific nature of esterases, however, it might be possible to carry over mechanistic conclusions from the studies with simpler esters. A favored formulation of this process by Bender and Kezdy is... 

The sulfates of saturated ketosteroids are readily split under the conditions of acid hydrolysis described above (Section III,1) which were found effective for the cleavage of glucosiduronates. However, their cleavage may also be accomplished under very much milder conditions, as was shown by Lieberman and Dobriner (79) and subsequently confirmed by Buehler et at. (14) (Table III, method A). Continuous extraction with ether at pH 0.7 for 24 to 48 hours gives a quantitative recovery of the free steroid. The hydrolysis of the sulfate esters takes place without inversion of stereochemical configuration (82). 

CHAllENGtl Show how you would carry out the following transformation in which the ester function at the lower left of the molecule is converted into a hydroxy group but that at the upper right is preserved. (Hint Do not try ester hydrolysis. Look carefully at how the ester groups are linked to the steroid and consider an approach based on transesterification.)... 

A very high sulfatase activity which permits the hydrolysis of the steroid ester. sulfates involved in estrogen biosynthesis. These ester sulfates arc mainlj dehydroepiandrosterone- and 16 -hydroxyde iydro-epiandrosterono-3 -sulfate. 

The hydrolysis of an ester moiety is regarded by many scientists as a most simple reaction, even sometimes armoying. This was also true for baker s yeast-mediated hydrolyses [307,308]. The first report of an ester hydrolysis has been published in the steroid field, and it was reported as an undesired side reaction [309]. Many different enzymes of baker s yeast may be responsible for the hydrolysis of ester moieties not... 

The asymmetric aUcoxycarbonylation of aUcenes is a reaction of particular interest, especially for vinylarenes, because it gives a two steps access (alkoxycarbonyla-tion, ester hydrolysis) to enantiomerically pure carboxylic acids from alkenes. For instance, a few arylpropionic acids such as (S j-Ibuprofen, (5)-Ketoprofen, and (5)-Naproxen, are popular non-steroidal anti-inflammatory agents [99]. Although good regio- and enantioselectivities have already been reported for asymmetric aUcoxycarbonylation, no systems, to the best of our knowledge, possesses both types of selectivities [100-104]. We tested ligands 7 in the asymmetric... 

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

Catalytic hydrogenation of the 14—15 double bond from the face opposite to the C18 substituent yields (196). Compound (196) contains the natural steroid stereochemistry around the D-ring. A metal-ammonia reduction of (196) forms the most stable product (197) thermodynamically. When R is equal to methyl, this process comprises an efficient total synthesis of estradiol methyl ester. Birch reduction of the A-ring of (197) followed by acid hydrolysis of the resultant enol ether allows access into the 19-norsteroids (198) (204). 

Replacement of halides with deuterium gas in the presence of a surface catalyst is a less useful reaction, due mainly to the poor isotopic purity of the products. This reaction has been used, however, for the insertion of a deuterium atom at C-7 in various esters of 3j -hydroxy-A -steroids, since it gives less side products resulting from double bond migration. Thus, treatment of the 7a- or 7j5-bromo derivatives (206) with deuterium gas in the presence of 5% palladium-on-calcium carbonate, or Raney nickel catalyst, followed by alkaline hydrolysis, gives the corresponding 3j3-hydroxy-7( -di derivatives (207), the isotope content of which varies from 0.64 to 1.18 atoms of deuterium per mole. The isotope composition and the stereochemistry of the deuterium have not been rigorously established. 

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