A-Homo steroids

A conformational analysis of various substituted A-homo-steroids is reported. The preferred conformation of the amide group in some acetamido-substituted steroids is of the type (5), with anti-periplanar orientation of C—H and N—H bonds the eclipsing of the C—H and C=0 bonds is similar to that accepted for acetates of secondary alcohols. 

Conformational studies of some A-homo-steroids, including the novel a-homo-5a-cholestan-2-one and its derivatives, and of 4aa-bromo-A-homo-5a-cholestan-4-ones (17), have been reported. 

Levisalles and co-workers have prepared A-homo-5a-cholestan-4-one by the dibromocarbene procedure starting with 3-methoxy-5a-cholest-2-ene. Wieland and Anner have converted 19-mesyloxy-A -3-keto steroids into... 

Johnson s procedure can be used to prepare A-homo-4a-ene-3-keto steroids or, more generally, any 7-membered ketone having an olefinic linkage. For simple saturated 6-ring ketones, Parham s procedure offers an alternate approach to the preparation of cycloheptenones. 

In the course of synthetic efforts aimed at obtaining 6j5-fluoro steroids, Kirk and Petrow treated a 3)5-acetoxy-6-raethyl-5a,6a-epoxide with boron trifluoride etherate and unexpectedly obtained a fluorine-free acetoxy ketone." Later transformations established that the product was the A-homo-B-norsteroid (104). 

A-Nor-B-homo steroids with different substitution patterns than those described above may be prepared by acid catalyzed cyclization of 3)3-hydroxy-5(10)-seco-cholest-tra/w-l(l0)-en-5-one acetate (134a) formed in 30-40% yield by mercuric oxide-iodine sensitized irradiation of cholestane-3j3,5a-diol... 

A-nor-5a-cholestan-2-one, 419 B-norcholestenone, 430 19-Norcholestenone, 281 B-norcholesterol acetate, 429, 430 D-nor-11-dehydrocorticosterone acetate, 441 D-nordesoxycorticosterone acetate, 441 A-nor-B-homosteroids, 395 C-nor-D-homo steroids, 400 C-nor-1U- (a-hydroxyethyl) -pregnane-... 

A detailed examination of OSO4 reactions with A -steroids has been reported." The A-ring conformation of the reactant or derived complex is important in determining the stereoselectivity of these reactions, and the major role of the proximate substituents is to anchor the appropriate conformation favouring a- or /3-attack. Studies on the stereochemistry of electrophilic attack on cholest-5-en-3-one continue." As with bromine chloride," appreciable /3-attack occurs and the 5/3,6j8-epoxide was isolated along with the previously reported 5a,6a-epoxide and the Baeyer-Villiger product, the A-homo-enol lactone (58). Base-catalysed... 

V. 10(5 -> 6pH)Abeostero ds (A-Homo-B-Norsteroids) / 389 Solvolysis of 5a,6a-epoxy-6-methyl steroids / 389 Pinacol rearrangement of 5a-hydroxy-6a-tosylates / 392 Summary / 394... 

Methods have been reported for the conversion of jervine into C-nor-D-homo-steroids that are functionalized at C-18.57-58 The key intermediate, aldehyde (27a), was prepared from 11-deoxojervine (25a) via the hexahydro-derivative (26a), as summarized in Scheme l.57 Alternatively, JV,0-diacetyl-ll-deoxojer-vine (25b) was reduced sequentially with Pt/H2 and with Rh/Pt/H2 and the product (26b) was converted into the aldehyde (27b) by irradiation of a solution of (26b) in benzene, in the presence of mercuric oxide and iodine.58 Further studies have been reported on the chemistry of C-nor-D-homo-steroids that are derived from jervine.59 Details of the formal conversion of jervine into testosterone have been published.60... 

Some 2-deoxy-analogues of rubrosterone have been reported.73 The synthesis commenced with a Bamford-Stevens reaction upon 3/3,17/3-diacetoxyandrost-5-en-7-one tosylhydrazone to yield the corresponding 5,7-diene. Successive chromic acid and selenium dioxide oxidation of this diene furnished the 2-deoxyrubrosterones (177 R1 = OAc, R2 = H, R3 = OH, X= 17/3-0Ac,H 5a-H) and (177 R = OAc, R2 = R3 = H, X = 17/3-OAc,H 5a-H) respectively. Alkaline hydrolysis of the latter derivative afforded an A-homo-B-nor-steroid (178). The rubrosterone (177 R1 = R2 = R3 = OH, X = O 5/3-H), which possesses antidiabetic activity, has been prepared by oxidative degradation of the cholestene (179), itself obtained from ecdy-sterone.74... 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

The Barton reaction (photolysis of a nitrite) has been applied to the C(20)-alcoholic derivatives (490) and (491) in the c-nor-D-homo-steroid series, with the results indicated (Scheme 22). "" In the 20)3-series, attack upon C(15) also... 

It has been shown that 7j8-fluoro-B-homo-steroids are much more stable than their 7jS-chloro-analogues. Aromatization of ring a of such 7)S-fluoro-B-homo-androstanes and -pregnanes, under various conditions, occurred without rearrangement of the carbon skeleton and without loss of fluorine. Whereas... 

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