Steroids, 16,17-epoxy

Low-valent metal salts, such as chromium(II) acetate and samarium iodide, have been reported to be useful. With chromium(II) acetate, a steroid epoxy ketone is efficiently converted to a p-hy-droxy ketone (equation 26). 

Among interesting olefin syntheses with ester phosphonates are those with the allenic aldehydes (141) and with the steroidal epoxy-aldehyde (142). The yield of allenic carboxylic esters has been increased to... 

Ring-opening of Epoxides. Diversity of results from the reaction of HF with some steroidal epoxy-ketones seems to stem from a critical dependence of reaction path on solvent.A 4, 5) -epoxy-3-ketone (76) reacted with HF in anhydrous chloroform to give the 5a-fluoro-4a-alcohol (78), probably resulting from acid-catalysed epimerization of an initially formed 5a-fluoro-4) -alcohol (77), the... 

Sonication greatly helps in the reduction of C-0 single bonds by metals. An aromatic dioxolane ring reacts with lithium, sodium, or potassium with cleavage of the benzylic C-0 bond. The ring cleavage of epoxides by aluminum amalgam is effected in aqueous ethanol in the presence of sodium formate. Examples were studied with steroidic epoxy ketones (Eq. 25). 

The steroidal epoxy compound 205 was reported to undergo rearrangement to the ketone 206, which subsequently underwent an oxa-di-Jt-methane reaction to give the cyclopropyl compound 207 along with its stereoisomer and other compounds (Scheme 39). °°... 

The steroidal 4/3-acetoxy-5/J,6/l/-epoxy-2-en-l-one system 546 was converted at room temperature into the 6/3-hydroxy-2,4-dien-l-one 547 by reductive elimination of the vicinal oxygen function, and the reaction has been applied to the synthesis of withanolide[352]. 

A third type of reduction of a-substituted ketones is typified by the expulsion of the substituent and the reduction of the keto function to form an olefin. Wolff-Kishner reductions of a-hydroxy, a-acetoxy, " a-halo, °° and a-epoxy (see below) ketones are the most frequently encountered steroid examples of this general class. ... 

This approach has been useful in obtaining C-1 oxygenated steroids and rather inaccessible 15-keto compounds. 16a-Hydroxy-A °kpi-egnanes have been obtained from the readily available 16a,17a-epoxy-20-ketones It has been shown °° that the product is a mixture of comparable amounts of the cis- and /ran -isomers (145,146), the structures of which were assigned on the basis of NMR measurements (ref. 200, see also ref. 306). 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

The effect of an a-substituted oxirane group on the optical rotatory dispersion of steroidal ketones should be interpreted with caution an inverted octant rule for a-epoxy ketones has been proposed/although recent data indicate that the normal octant rule may still be valid. 

The preparation of other 6-aIkylated steroids has also been accomplished with 5,6-epoxides. Thus treatment of 3,3-ethylenedioxy-5a,6a-epoxy steroids (6) with acetylenedimagnesium bromide,propargylmagnesium bromide " or phenylmagnesium bromide, gives the corresponding 6 -ethynyl-, 6j5-propargyl- and 6/ -phenyl-3,3-ethylenedioxy-5a-ols. 

Keto steroids can be obtained in excellent yields via the Beckmann degradation of 17a-hydroxy-or 16a,17a-epoxy-20-ketopregnanes. In the case of the 17-hydroxy compounds, substituents at C-16 readily survive e.g., 16 -Br, 16jS-Cl, Iba-OAc). The 16,17-oxido-20-oximinopregnanes produce 16a-acetoxy-17-ketones. 

Photochemical processes provide an alternative approach to 10(54)n6eo-3,5-diketones. Thus, irradiation of saturated or l,2-unsaturated-4,5-epoxy-3-keto steroids such as (129) and (130) produces 3,5-dioxo-10(54)<3Z)eo-... 

Diketo steroids have been prepared by air oxidation of 3-keto-5i5-steroids in potassium /-butoxide-t-butanoF or by hydrolysis of 4,5-epoxy-3-ketones followed by dehydration. However, the most general synthesis is that used by Camerino et al. to prepare Vketo-A-norandrostanes and pregnanes. Hydroxylation of 17a,20.20,21-bismethylenedioxypregn-... 

Enolate trapping, 97 Epoxidation of steroidal dienes, 7 Epoxidation of steroidal monoenes, 2 4, 5/3-Epoxycholestan-3 -ol, 27 5a,6a-Epoxy-5a-cholestan-3 -ol, 82 5a,6a-Epoxy- 17-cy anoandr ost-16-en-3 jS-ol acetate, 20... 

Rearrangement of a,/B-epoxy ketones to ftdicarbonyl isomers, 307 Reductive alkylation, 97 Reductive cleavage of halo ethers, 264 Reductive degradation of 19-substitutional steroids, 277, 278 Reformatsky reaction, 139 Removal of the C-10 substituent in steroids. 272... 

To approximately 1.3 g of hydrogen fluoride contained in a polyethylene bottle and maintained at -60°C was added 2.3 ml of tetrahydrofuran and then a solution of 500 mg (0.0012 mol) of 6a-fluoro-9/3,11/3-epoxy-16a-methyI-17a,21 -dihydroxy-1,4-pregnadiene-3,20-dione-2T acetate in two ml of methylene chloride. The steroid solution was rinsed in with an additional 1 ml of methylene chloride. The light red colored solution was then kept at approximately -30°C for 1 hour and at -10°C for 2 hours. At the end of this period it was mixed cautiously with an excess of cold sodium bicarbonate solution and the organic materiai extracted with the aid of additional methylene chloride. 

During synthesis of the hormone rf-aldosterone, 20,21-dihydroxy-lip,18-epoxy-5a-pregnan-3-one diacetate was oxidised to the 3-oxo acid by stoich. RuOy CCl [78, 79], Oxidation of a substituted pyrrolidine to a pyroglutamate, part of the total synthesis of the antibiotic biphenomycin B, was effected by RuO /aq. Na(lO )/ EtOAc [102], Oxidation of a number of A-5 steroids to enones was effected by RuClj/TBHP/cyclohexane [391] safety aspects of these large-scale reactions were examined, as in the preparation of the antibacterial squalamine [186],... 

The first synthesis of 15-oxygenated-14/3-A -steroids employed the BF3-catalysed rearrangement of a 14a, 15a-epoxy-A -compound (252) to the 15-oxo-14/3-A -compound (253) which on hydride reduction gave the epimeric 15-... 

Sodium toluene dispersion of, 55, 65 Sodium p-toluenesulfinate, 57, 103 Spiro[4 n] alkenones, 58, 62 Spiro[cyclopentane-l,l -indene] 55, 94 Squalene, 56, 116 Squalene, 2,3-epoxy, 56, 116 Stannic chloride, 56, 97 Steroids synthesis, 58, 85 E Stilbene, 55, 115,58, 73 z-Stilbene, 58, 133 Styrene, 56, 35,58, 43 Styrene glycol, 55, 116 Styrene glycol dimesylate, 55, 116 Succinic acid, 58, 85 Succinic anhydride, 58, 85 Sucunimide, 56, 50, 58, 126 Succimmide, Vbromo, 55, 28, 56, 49 SULFIDE CONTRACTION, 55, 127 Sulfide, dimethyl-, 56, 37 SULFIDE SYNTHESIS, 58, 143,58, 138 SULFIDE SYNTHESIS ALKYL ARYL SULFIDES, 58, 143 SULFIDE SYNTHFSIS DIALKYL SULFIDES, 58, 143 SULFIDE SYNTHESIS UNSYMMETRI-CAL DIALKYL DISULFIDES, 58, 147 SULFONYL CYANIDES, 57, 88 Sulfur tetrafluoride, 57, 51... 

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