Steroids derivative formation

Several of these steroid derivatives underwent elimination of phosphorodichloridate anion, giving hydrocarbon products, rather than ester formation when treated with methanolic pyridine. Pyrophosphoric acid itself has been used to phosphorylate (2-hydroxymethyl)pyridine. ... 

They developed a continuum elastic-free energy model that suggests these observations can be explained as a first-order mechanical phase transition. In other recent work on steroids, Terech and co-workers reported the formation of nanotubes in single-component solutions of the elementary bile steroid derivative lithocholic acid, at alkaline pH,164 although these tubules do not show any chiral markings indicating helical aggregation. 

Barton and co-workers have explored tertiary carbon atom functionalization by trifluoromethyl hypofluorite, mainly in chloroform, on various steroid derivatives however, the site of functionalization strongly depends on the structure of the steroid and the functional group.16-18 e.g. formation of 2. 

The method was subjected to a comparison between two different laboratories. Table 10.1 shows the results obtained and indicated that there was no significant difference between the values obtained in the two laboratories. The use of this method as opposed to some of the others reported in the literature deserves comment. Generally, most investigators describe derivatization as a necessary step in obtaining usable chromatograms. However, derivative formation is not always a reliable method, but appears necessary in biological samples with low steroid levels to increase sensitivity as well as selectivity. 

Method. 0.2 ml of an ethanolic solution of hydrochloric acid (0.65 ml of concentrated hydrochloric acid per litre of absolute ethanol) is added to the dry keto steroid in a small test-tube [103,104]. 0.2 ml of a solution of DNS-hydrazine (2 mg/ml in absolute ethanol) is then added. The contents of the test-tube are heated in a bath in boiling water for 10 min for hydrazone formation. The tube is cooled and 0.2 ml of sodium pyruvate (5 mg/ ml in absolute ethanol) is added to destroy the excess of DNS-hydrazine. The tube is permitted to stand at room temperature for 15 min. 6 ml of diethyl ether and 3 ml of Q.5-N aqueous sodium hydroxide are then added and the tube is shaken. The diethyl ether layer is removed and evaporated to dryness. The residue is dissolved in a small volume of chloroform (0.2-0.5 ml) for TLC analysis. The keto steroid derivatives are separated on layers of Alumina G (Woelm) (thickness, 250 fim) which have been activated at 120 °C for 30 min. The solvent consists of dioxane-chloroform (1 9). The separated derivatives are observed under UV light at 366 nm. The limits of detection are in the 1-2 nmole range for each steroid. 

Although steroid derivatives are in general remarkably reactive toward Mannich. synthesis, some cases of unexpected absence of activity of the. substrate, as well as the formation of methylene-bis-derivativcs R—CH2—R, " polyamipomethylated... 

These experiments were undertaken in a similar manner to those described by Brady and Sanders for measuring relative binding affinities of metals with steroid derivatives by ESI-MS. Titrations with zinc and copper solutions were carried out on patellamides C and A by sequential addition of 0.25 equivalents of the metal solutions to the peptides (cone. 0.02 mg/mL in MeOH). These titrations were monitored by measuring the formation of the metal species as well as the loss of the uncomplexed peptides, using both the full spectrum and the selected ion mode of the instrument in parallel, as the ionisation efficiency of these species were very different. Once fully complexed zinc species were obtained for each peptide, copper solution was then titrated into these at a rate of 0.25 equivalents to again observe the competition effects. 

Catalyzed reductions with ammonium formate proceed with retention of configuration, at least for the case of nitro compounds. Treatment of steroid derivative (12) with ammonium formate in methanolic solution and a catalytic amount of palladium on charcoal gave exclusively amino steroid (13), as shown in equation (13). A similar technique has been used to produce members of the ephedrine family. 

O, y6-Unsaturated ketones of the structure RR C=CHCOCH3 yield on treatment with sodium amalgam a mixture of products, including tetrahydrofurans (V) and dihydrofuran derivatives (VI), glycols (VII), e-diketones (VIII), and ketols (XI) [85-87]. The ratio between the products depends on R and R bulky groups as found in steroids favor formation of glycols rather than of e-diketones [88]. The reactions leading to these products are similar to those discussed in Chapter 10. 

Dienes participate in the Vilsmeier-Haack reaction as illustrated by formation of aldehydes (40) and (41) from steroid derivatives (42) and (43) respectively. Carbon-carbon bond migration also occurs in these two reactions and the corresponding aldehydes (44) and (45) are produced as by-products. 1,3,5-Trienes also yield aldehyde derivatives in the Vilsmeier-Haack reaction. ... 

In the C -C bond formation of more complex cyclic systems, such as the steroid derivative ethyl 3/J-(/tTt-butyldimethylsiIyloxy)-20-phenylseleno-5-pregnen-21-oate, 1.2-induction is also effective 10. Reaction with tributyl(2-propenyl)stannane yields the diastcrcomeric steroids in a ratio of 90 10. 

The reductive amination of ketones with a steroid structure makes possible the formation of an amino or substituted amino function on various carbon atoms of the steroid skeleton. In this case, different oxo functions are simultaneously present in the same steroid skeleton and selective reductive amination can frequently occur, because of the differences in steric hindrance of the carbonyl groups. Thus, the reductive amination of steroid derivatives often takes place with high stereoselectivity. The catalyst commonly used for the reductive amination is palladium on charcoal35 38. 

Prior to GC-MS analysis, the steroid fractions require derivatization. Ketosteroids are usually converted to oximes using methoxylamine, benzylamine, or hydroxylamine hydrochloride in pyridine. Two epimers of the oxime are formed (E and Z). Hydroxyl groups are then derivatized as trimethylsilyl (TMS) ethers. After formation of the TMS derivative, the extract is further purified by chromatography on a small column of Lipidex 5000. An alternative to TMS is the use of t-butyldimethylsilyl (t-BDMS) ethers, but although conferring desirable mass spectrometric properties, namely an intense M — 57 ion, the t-BDMS group is 42 U heavier than TMS and the formation of poly t-BDMS ethers may increase the relative molecular mass of the steroid derivative beyond the mass range of small quadru-poles. 

In the context of the proposed steroid methodology, the ability to alter the nature of the Michael donor or acceptor would permit access to synthetically useful steroid derivatives that could not be achieved by semisynthetic means. The variation in the structure of the Michael acceptor for the reactimi with the six-membered p-ketoester was investigated first (Scheme 6). Craisistent with the results obtained for the H-catalyzed formation of 14a, comparably high yields and high selectivities were achieved for the formation of structurally similar adducts 14b and 14c. Altering the remote p-substitution of enone 13 did not affect the selectivities, as the reaction of ( )-oct-3-en-2-one also resulted in highly selective formation of the corresponding Michael adduct 14d. 

Extraction and derivative formation. The analytical procedures used for the recovery and purification of the steroids from urine have been described previously (2). Trimethylsilyl (TMS) ethers were prepared of the steroids prior to gas chromatographic analysis. 

Any kind of biological response due to the compound, either in vivo or in vitro systems, is associated with the interaction of the appropiate receptor and the compound. This is one of the most important steps. 3 in the case of the steroidal hormones, formation of the receptor - hormone complex is essential. So the polymeric derivative needs to be hydrolyzed... 

An illustrative example of a stereoselective reduction with diimide is the conversion of the steroid derivative 82 into 83 as the only observed isomer (Equation 19) [61]. This transformation was used as a convenient stereo-and regioselective method for isotopic labeling of 83. Use of diimide avoided the formation of diastereomeric mixtures and prevented partial unwanted isotopic labeling at the allylic position, both of which had otherwise been observed with use of standard heterogeneous catalytic hydrogenations. 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

The stabilization reactions of alkylcarbenes were used preparatively in some cases. The diazirine derived from adamantanone gave the dehydroadamantane (2l7) thermally in 96% yield 73ZOR430). Alkene formation was reported for a steroid with its C-3 atom part of a diazirine ring. At 140 °C a A-2-unsaturated steroid was formed 65JA2665). 

---