D-Nor steroids

Ring-contraction in a D-nor steroid to form a fused cyclopropane derivative J. Meinwald and J. Ripodl, J. Am. Chem, Soc., 89 (1967)... 

Interest in D-nor-steroids derives both from their biological activities, and also from their use as models for studies of carbonium ion rearrangements, since they possess cyclobutane rings which are held in fixed conformations by virtue of the fra s-fusion to ring c. Analyses of the stereoisomers (112a) and (112b) reveal that in both cases the cyclobutane rings are puckered. 

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-... 

The photochemistry of some isomeric D-nor-16-keto steroids has been reported by Quinkert and co-workers,1129)... 

Abb. 2. Die typischen Photo-Reaktionen eines Vierring-Ketons, aufgezeigt am Beispiel eines D-Nor-16-keto-Steroids 21> der eingeklammerte y.S-ungesattigte Alde-hyd wurde nicht aufgefunden... 

VII. 14(13 -> 12aH)y46eosteroids (C-Nor-D-Homo Steroids) / 400 By solvolysis of 12/ -methylsulfonyloxy steroids / 400 By fragmentation-rearrangement of 12-tosylhydrazones / 402... 

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... 

The mechanism of formation of the c-nor-D-homo-steroids from solanidanine alkaloids has been discussed63 and the toxic principles of V. album have been reviewed.64 The transformation of jervine into c/d-trans C-nor-D-homo-steroids has been described.65 The 13C n.m.r. spectra of four ceveratrum alkaloids have been recorded and interpreted.66... 

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... 

The Barton reaction" has been applied successfully to functionalize the methyl group C(18) in a D-homo-c-nor-steroid." (see Part II, Chapter 1, ref. 304). 

Various partial synthetic approaches to veratramine (456) have been reported.The full paper on the synthesis of (456) has now appeared. The route which was followed (Scheme 35) involves condensation of the D-homo-c-nor-steroid fragment (452) with the enamine (453), yielding, among others, the desired intermediate (454). Reduction of the carbonyl group in (454), mild hydrolysis, and separation of the correct isomer gave, after acetylation and... 

Angular alkylations of 1-decalone enolates provide important models for angular alkylations of 18-nor-D-homo steroids. The manner in which structural modifications influence cisUrans product ratios in alkylations of various enolates of 1-decalones containing blocking groups at C-2 has been thoroughly investigated and reviewed. ... 

Interest continues in the preparation of c-nor-D-homo-steroids from readily available Veratrum alkaloids. In this connection the jervine-derived enamine (14) gave the ketone (15) (40%) on sensitized photo-oxygenation. Similarly, enamine (16) gave the expected ketone (17) and the ring-contracted product (18). ... 

D-homosteroid (15) in 24% yield together with some of a double-bond isomer. Ozonolysis to a triketoaldehyde followed by acid cyclization gave the 19-nor-steroid. 

Jervine, one of the most readily available Veratrum alkaloids, was the starting material for the synthesis of C-nor-D-homo steroid hormone analogs. Kupchan and Abu El-Haj (31) degraded jervine to the 3 8-hydroxy-14(1312 8-H)-a6eo-androst-5-ene-ll,17-dione (28) and prepared 17a-hydroxy-14(13 12)3H)-a6eo-pregn-4-ene-3,ll,20-trione (29) and its 17(8-isomer (30). 

A synthetic approach to the alkaloids of C-nor-D-homo steroidal skeleton (veratramine, jervanine, and cevanine type) has been examined by Huffman and associates (57). They attempted to prepare compounds 75 and 76 from the exocyclic olefin 77. 

The configuration 8(S-, 9a-, 12a-, 14a-hydrogen in veramarine was inferred from the analogy with the other alkaloids of the cevanine group and from the consideration of biogenesis of the G-nor-D-homo steroidal skeleton (56). 

A number of modified steroids are known in which one of the rings is contracted by one carbon atom relative to the normal tetracyclic steroid nucleus via diazotization. Irradiation of diazoketones affords D-nor-, A-nor, and A-bis-nor-androstane carboxylic acids (22 9-231).20,46... 

Covey, D.F., W.F. Hood, and P.C. McMullan (1986). Studies of the inactivation of human placental aromatase by 17a-ethynyl-substituted lOP-hydroperoxy and related 19-nor steroids. Biochem. Pharmacol. 35, 1671-1674. 

In earlier work it has been found that the C-18 methyl group of the c-nor-D-homo-steroid (23) could be functionalized by photolysis in the presence of iodine, lead tetra-acetate, and sodium carbonate, when (24) was produced.The usefulness of the hypoiodite reaction " for the derivatization of c-nor-D-homo-steroids... 

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