Steroids trans form

All rearrangements of 20-oximino steroids have thus far given only the product arising from migration of the large steroid residue rather than the smaller C-21 methyl group. This is a consequence of the fact that only the oxime with the hydroxyl furthest removed, and therefore trans, to the bulk of the steroid, is formed. 

Phenyliodosochloride-azide [C6H5l(Cl)N3] reacts with cholesteryl acetate to give a cis addition product, the 5a-chloro-6a-azido-derivative. Other A -unsaturated steroids gave products of both cis and trans addition the corresponding dichlorides were also formed. N-Chlorourethane adds on to olefinic steroids under free-radical conditions. 5o(-Cholest-2-ene (161) gave the 2p-chloro-3a-urethane (162), which reacted with base to form the N-ethoxycarbonyl-aziridine (163) and then 2a,3a-aziridino-5a-cholestane (164). A -Unsaturated steroids similarly form the 5a-chloro-6/ -urethane derivatives, from which the 5. 6/ -aziridino-steroids are available. 

Addition of hydride ion from the catalyst gives the adsorbed dianion (15). The reaction is completed and product stereochemistry determined by protonation of these species from the solution prior to or concurrent with desorption. With the heteroannular enolate, (13a), both cis and trans adsorption can occur with nearly equal facility. When an angular methyl group is present trans adsorption (14b) predominates. Protonation of the latter species from the solution gives the cis product. Since the heteroannular enolate is formed by the reaction of A" -3-keto steroids with strong base " this mechanism satisfactorily accounts for the almost exclusive formation of the isomer on hydrogenation of these steroids in basic media. The optimum concentration of hydroxide ion in this reaction is about two to three times that of the substrate. 

In very dilute base or, preferably, in the presence of weak bases, the homoannular enolate (16) is formed which can be adsorbed in either a cis (17) or a trans (18) manner. In this case the presence of a methyl group results in a slight favoring of trans adsorption, thus leading to the formation of a slight excess of the m-product as is observed on hydrogeneration of A" -3-keto steroids in the presence of triethylamine. ... 

An important stage in the synthesis has been reached. It was anticipated that cleavage of the trimethylsilyl enol ether in 18 using the procedure of Binkley and Heathcock18 would regiospecifically furnish the thermodynamic (more substituted) cyclopentanone enolate, a nucleophilic species that could then be alkylated with iodo-diyne 17. To secure what is to become the trans CD ring junction of the steroid nucleus, the diastereoisomer in which the vinyl and methyl substituents have a cis relationship must be formed. In the... 

Because the reactive intermediate 1277 and methanesulfenyl chloride 1278 are electrophiles, they can react with olefins [72-75]. Thus d -steroids give rise to 6-)9-methylmercapto-zl" -steroids [74]. trans-6-Phenylcyclohex-3-ene-3-carboxyUc add 1291 reacts with DMSO/MesSiBr 16 to form, via 1292, the lactone 1293 in 87% yield, whereas attempted bromolactonization of 1291 affords only 59% 1294 [75] (Scheme 8.29). 

With two y,8 double bonds, two a,/3 double bonds, and the possibilities of cis and trans ring fusions with syn and anti configurations, 20 isomeric dimers are possible. Surprisingly, only one product is formed in a head-to-tail fashion. The sole product of the irradiation of the 3,5-diene-7-ketosteroid (76), however, is the head-to-head dimer. The specificity and mode of addition arise presumably through the effect of the specific environment of the chromaphore. The dimerization of (75) is believed to involve the addition of the a,fi double bond of a photoexcited molecule to the less hindered y,8 double bond of a ground state molecule. The photocondensation of (76) with cyclopentene, in which steric hindrance should not be a controlling factor, was found to yield a cyclobutane product involving the a,/ bond of the steroid in contrast to dimerization across the y,8 bond. 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

The marked stereoselectivities and clean solid-state reactions of oxiranes were used for synthetic purposes in the steroid field. The stereospecifically obtained trans-chlorohydrins 147 ensue quantitatively from the crystalline 5a,6a-epoxides 146 with gaseous HCl [77]. Similarly, the crystalline 16a,17a-epoxide 148 reacts with gaseous HCl to yield exclusively the traws-chlorohydrin 149 which easily loses HCl to re-form the starting epoxide 148. Therefore, an equilibrium situation is reached in that case [77] (Scheme 16). 

Vitamin A is essential for proper functioning of the retina, for the integrity of epithelial tissue, for growth and bone development and for reproduction. For vision the active vitamin appears to be retinal as the chromophore of both rods and cones is 11-cis-retinal which, in combination with the protein opsin, forms the photoreceptor rhodopsin. Retinoic acid is the active form associated with growth, differentiation, and transformation. Both all-trans and 9-cis retinoic acid act as a steroid hormone to affect cellular differentiation, especially for morphogenesis, reproduction and for immune responses. At... 

These considerations apply to all cycloalkane derivatives, including steroids. However, the chair form of a ring is inherently more stable than the boat form. Moreover, the fnsed-ring natnre of the system lends it a very considerable rigidity, and cis-trans isomerization wonld necessitate the breaking and formation of covalent bonds. Therefore, steroid snbstitnents maintain their conformation at room temperature, whereas cyclohexane substituents usually do not. Steroids are classified according to their substituents in addition to their occurrence. 

Iodine azide, on the other hand, forms pure adducts with A2-, A5- and A16-steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the trans-diaxial adducts of the A2- and A5-olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction.114 Lithium aluminum hydride accomplishes aziridine formation from the A16-adducts, i.e., 16/ -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

Acetoxy-17a-ethynyl steroids rearrange to 21-acetoxy-17,20,21-allenes under the influence of Ag+ catalysis, with equal amounts of both possible isomers being formed.19 Acid or base hydrolysis then gives the trans-21-aldehyde in high overall yield. 

Numerous nanostructures such as nanorods, nanotubes, or nanorings have been obtained by this approach. In particular, the use of organoge-lators as directors to control the morphologies of the aggregates has been explored recently. Cholesterol- and phospholipid-thethered trans-styl-benes are able to gelate different organic solvents in which the steroid and the lipid units serve as templates to form one-dimensional stacks. 

In natural steroids, there are examples of the A/B ring fusion being trans or cis, or having unsaturation, either A4 or A5. In some compounds, notably the oestrogens, ring A can even be aromatic clearly there can then be no bridgehead substituent at C-10 and the normal C-10 methyl (C-19) must therefore be lost. All natural steroids have a trans B/C fusion, though cis forms can be... 

As an extension of this work, Mattay et al. have used this methodology for the construction of unnatural steroid analogues [41]. The polycyclic framework was build-up via a cascade cyclization of the silyl enol ether 32 using DCA as sensitizer (Sch. 19). The two major products 33 were formed with remarkable high trans, //-stereoselectivity. 

Figure 2-12B. The ring junction between rings A and B is trans in some steroids, cis in others. The junctions between B and C and C and D are normally trans. Substituents that lie above the plane, as drawn in Figure 2— 12C, are named p, those below the plane, a. The 3-OH group in cholesterol (Figure 2-12C) is the -configuration, and it is this group that may form ester linkages. The composition of the plant sterols is given in Figure 2-13. Part of the sterols in natural...

Electrophilic Addition.—rrans-Diequatorial diols are not readily prepared from olefins in the steroid series. The ring-opening of epoxides generally gives trans-diaxial products, whereas acyloxonium ions (65), formed during the Prevost... 

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