D-Homo steroids

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-... 

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... 

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... 

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). ... 

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). 

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... 

A report mentions the synthesis of intermediates of type (68) and (69) for the preparation of c-nor-D-homo-steroids." Compounds of general formula (70)... 

The hydroxy-nitrone (26), the preparation of which from jervine was described earlier, was converted into the oxaziridine (27) on treatment with benzoic anhydride in pyridine. The alternative oxaziridine (28) was the sole product on irradiation of the nitrone at 285 nm. The oxaziridine (28) was reconverted into nitrone (26) in quantitative yield on standing at room temperature in the dark (Scheme 3). Studies continue on the chemistry of c-nor-D-homo-steroids derived by degradation of jervine. ... 

The reactions of bromohydrins in the cholestane series with Ag20 have been shown to depend markedly on the conformation of the bromine. Thus, for example, the 6a-bromo-7 -hydroxy-compounds (107) and (108), which have the equatorial bromine, gave the B-nor-aldehyde (110) whereas the 6/8-bromo-7/S-hydroxy-compound (109) gave the 7-oxo-compound (111) via a hydride shift. Hydrolysis of the dipotassium 5)3-pregnane-3a,20a-diyl sulphate in 3N-HC1 gave the D-homo-steroids (112) and (113) in addition to the expected... 

The C-nor-D-homo steroid alkaloids are formed from steroids by rearrangement of the ring system. The exact pathway is, however, still unknown. The alkaloids are poisonous to animals and act as feeding deterrents (E 5.5.3). They are effective insecticides. 

New synthetic approaches to the ABCD ring systems of C-nor-D-homo-steroids have also been devised (see Figure 12). An A- to D-ring sequence by Brown and Lebreton uses hydrazone 167 (accessible from the classical Wieland—Miescher ketone, structure not shown) as a starting material. The C-ring was introduced via the aUylation of the corresponding hydra-zone with chloride 168, ozonolysis, aldol condensation, and olefin... 

---