Synthesis of heterocyclic steroids—V

Biological activity in steroids possessing nitrogen atoms: recent advances

“…Apart from new aza-steroids and new homo aza-steroids in which a nitrogen function has been substituted for a ring methylene group (for example, Engel & Rakhit, 1962;Huisman, Speckamp & Pandit, 1963;Kutney, Johnson & Vlattas, 1963 ;Kutney, Vlattas & Rao, 1963 ;Mazur, 1963 ; Morisawa, Kishida & Tanabe, 1963 ;Shoppee, Lack & Roy, 1963;Shroff, 1963;Uskokovic, Toome & Gut, 1962) prepared since the field was last reviewed (Rosseels, 1961 ;TokCs, 1963), several diaza-steroids have been prepared. These embrace both the heteroannular type (Doorenbos & Singh, 1961 ;, giving an extension of the earlier work leading to a diazaequilenin-like molecule (Bhide, Tikotkar & Tilak, 1960), and the homoannular type in which a carbocyclic ring of the steroid nucleus can be considered to have been replaced by a pyrazole ring (Vida & Gut, 1963a), a pyrimidine ring (Caspi & Piatak, 1963a) or a pyridazine ring (Caspi, Grover & Piatak, 1963), thus extending earlier work in which ring A of the steroid nucleus was replaced by substituted pyridazine rings (Weisenborn, Remy & Jacobs, 1954). A further extension of this type of replacement of ring A of the steroid molecule is represented by the preparation of compounds in which an isoxazole ring is the replacing entity (Vida & Gut, 1963b).…”

Ab → Abc → Abcd

“…The tricyclic diester 160 was converted into the keto ester 161 in four steps. The latter was next transformed into the olefinic ketone 162 by a series of reactions, in which a three-carbon chain was added while the ketone group was protected as 166 167 168 Scheme 3-15 the ketal. Cyclization was effected by heating the ketone 162 at 350° C, when the 18-nor-17-methyl compound 164 was obtained in 69.5% yield.…”

“…As a part of the work directed toward the total synthesis of heterocyclic steroids, Tilak and co-workers [165,166] synthesized di-B-nor-6oxaequilenin (190), the furano analog of equilenin (Scheme 3-17). The starting material was resorcinol, which was converted into the ketone 189 via y-(2,4-dihydroxybenzoyl)-butyric acid 188.…”

Synthesis of the Indole Nucleus

“…"~~ This enehydrazine 341 is difficult to indolize, as might be expected on both steric and electronic grounds, and was unaffected by boiling acetic acid.2i4 In fact, when the phenylhydrazone of 4-0x0-9-methyl-I ,2,3,4-tetrahydrocarbazole was treated with concentrated hydrochloric acid or with boron trifluoride, only hydrolysis to the original 4-oxotetrahydrocarbazole occurred. 274 However, when 341 was heated under vacuum at 360°, it indolized and simultaneously dehydrogenated to form not the 3H-indole expected from structure 341, but the 1H-indole 94, thus showing that 341 rearranged to the tautomeric enehydrazine 342 which then indolized in preference to 341 (Scheme 26). Upon attempted indolization, the monoarylhydrazones of acyclic 1,3-diketones 343 (R = H, R' and R" = alkyl) do not provide indoles but instead 316 Chapter I1 form pyrazoles 344.l0.…”

“…206 Carlin's an10gy'~l between the o-Claisen rearrangement and the Fischer indole synthesis can be clearly seen when one considers structure 129 and the 274 Chapter II 169 corresponding structure 169 from the rearrangement of ally1 phenyl ether (Eq. 48).…”