Keto-4,9-diene Steroids

The y, 5-double bond of a conjugated keto-diene may be selectively hydrogenated over catalysts, offering useful synthetic applications. Hydrogenation of dienone 16 affords 17 as an intermediate in the total synthesis of steroids. The disubstituted double bond is reduced more readily than the tetrasubstituted double bond in a nonpolar solvent to prevent participation of the carbonyl groups ... 

Keto-l,4-Diene, 3-Keto-4,6-Diene, and 3-Keto-4,9(ll)-Diene Steroids... 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

Oxidation of the 3-hydroxy-A systenli with manganese dioxide in refluxing benzene affords a moderate yield of the corresponding 4,6-dien-3-one. These vigorous conditions also suffice to cleave the corticoid side chain (17a,21-dihydroxy-20-ketones) to give 17-keto steroids. ... 

Many a,/ -unsaturated keto steroids undergo conjugate addition and thereby provide a unique route to aziridines. Treatment of 3j5-hydroxypregna-5, 16-diene-20-one acetate (48) with methoxyl-or ethoxylamine in ethanol under... 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

Dehydrogenation of 3-ketosteroids.2 By use of this method for generation of the reagent, dehydrogenation of 3-keto-steroids to A1,4-diene-3-ones can be a catalytic process with respect to the diselenide. Use of m-iodosylbenzoic acid is experimentally convenient, since the m-IC6H4COOH formed is easily separated from the ketonic product. 

Dehydrogenation of 3-kelo steroids. The dehydrogenation of 3-keto steroids to l,4-diene-3-ones with benzeneseleninic anhydride (8, 31) can be carried out in comparable yield by use of a process in which the benzeneseleninic anhydride is used in catalytic amounts and is continuously regenerated from diphenyl diselenide by oxidation with iodylbenzene. In practice, m-iodylbenzoic acid is a more convenient reagent, since m-iodobenzoic acid is easily recovered. 12-Keto and 12-hydroxy steroids arc oxidized by the catalytic system to A9(1 - -keto steroids in high yield. In fact, methyl desoxycholate (1) can be oxidized in this way directly to the trienedione 2 in 64% yield.1... 

Double dehydrogenation and even complete aiomatization of the A-ring of 34iydroxy or 3-keto steroids can also be etiected the latter is of special interest in the preparation of estrogens, for example the conversion of the diene (60) to the a-estradiol derivative (61 equation 19) by Proactinomyces glob-erulaP ... 

Protection of keto groups. Fried and Nutile used the methoxyimino derivative (2) for protection of the A - -diene-3-one system of the steroid (1). Conversion to... 

Section 6.5). It should be noted that 1,4-diene-3-ketosteroids react much less readily with isonicotinic acid hydrazides than do 4-ene-3-keto steroids . 

Alkylation of the metallated enol derived from 52 with m-methoxy-phenylethyl-iodide to afford the tricyclic jj-keto ester 53, followed by cationic cydization of this to furnish the steroid derivative 54, warrants particular attention. Corey and colleagues have recently published another total synthesis of 40 [82], beginning with an enantioselective Diels-Alder reaction between Dane s diene 14 and dienophile 61. An oxazaborolidinium salt (see Section 1.3.2.3) was used as an efficient catalyst (Scheme 1-14). 

Steroidal 3-keto-4,4-dimethyl-5,7-dienes (3) also form 1 1 adducts (4) with PTAD, but of a different type. These are decomposed by ethanolic HCl or by BF3 etherate to 5,7,14-triene-3-ones (5) and tetrahydro-4-phenyltriazole-3,5-dione. 

Adducts of steroidal 5,7-dienes (3, 223-224). The adducts of steroidal 3-keto-5,7-dienes (1) are decomposed at 20 in benzene containing BF3 etherate to 4,6,8(14)-triene-3-ones (2) in unspecified yield. 

---