Heterocyclics steroids, heterocyclic

Dihydro-1-vinylnaphthalene (67) as well as 3,4-dihydro-2-vinylnaphtha-lene (68) are more reactive than the corresponding aromatic dienes. Therefore they may also undergo cycloaddition reactions with low reactive dienophiles, thus showing a wider range of applications in organic synthesis. The cycloadditions of dienes 67 and 68 and of the 6-methoxy-2,4-dihydro-1-vinylnaphthalene 69 have been used extensively in the synthesis of steroids, heterocyclic compounds and polycyclic aromatic compounds. Some of the reactions of dienes 67-69 are summarized in Schemes 2.24, 2.25 and 2.26. In order to synthesize indeno[c]phenanthrenones, the cycloaddition of diene 67 with 3-bromoindan-l-one, which is a precursor of inden-l-one, was studied. Bromoindanone was prepared by treating commercially available indanone with NBS [64]. 

In order to study heterocyclic steroid analogues, such as the 7,11-dithiaazasteroid analogues, Fravolini developed the synthesis of new heterocyclic ring systems tri- and tetracyclic 2,1-benzothiazines <82JHC1045>. Intermediate 137 was prepared from 1-methyl-4-oxo-lH-2, -bcnzothiazinc-4(3f/)-onc 2,2-dioxide 37 and thioglycolic acid and could be converted into 6-methyl-4-oxo-3,4-dihydro-2//,6//-thiopyrano[3,2-c][2,l]benzothiazine 5,5-dioxide 138 by cyclization with polyphosphoric acid. The reaction of 138 with dimethyl... 

Total Synthesis of Heterocyclic Steroidal Antibiotics , H. O. Huisman, in MTP International Review of Science, Organic Chemistry Series One , ed. D. H. Hey, Butterworth, London, 1973, vol. 8, pp. 235-267. 

Approaches to Total Synthesis of Heterocyclic Steroidal Systems H. O. Huisman, Angew. Chem., Int. Ed. Engl., 1971,10, 450-459. 

Makhluf J. Haddadin was born in Main, Jordan. He holds B.S. and M.S. degrees (Professor C. H. Issidorides) from the American University of Beirut and a Ph.D. degree from the University of Colorado, USA (Professor A. Hassner). He was a research fellow at Harvard University (Professor L. F. Fieser). The art of heterocyclic chemistry has been his main hobby as he worked on heterocyclic steroids, isobenzofurans, isoindoles, quinoxaline 1,4-dioxides (the Beirut reaction), pyridazines, tetrazines, 277-indazoles, and other heterocycles. He rejoined his alma mater in 1964 and currently serves as professor of chemistry. He was vice-president for academic affairs (1987-99). 

The syntheses and biological activity of ring-A heterocyclic steroids have been reviewed. The JV-cyano-2-aza-A-norandrostane (333) was synthesized from the dibromo-seco-compound (331) via the JV-phenyl-2-aza-A-norandrostane (332) (Scheme 17). The mixture of iodoisothiocyanates (334) and (335) (see ref. 

As a result of this first report, a large number of compounds containing an isocyclic or a heterocyclic ring fused tc the steroid skeleton were prepared and tested for androgenic and anabolic activity. Included are steroidal isoxazoles [205], thiazoles [94], pyrroles [206], pyrimidines [207,208], oxazines [209], thiazenone [92], quinoline [107], pyridine [122], and furazane [121], all prepared by the fusion of the heterocyclic ring to ring A. Several bis heterocyclic steroids were also prepared by... 

A detailed survey of total syntheses of heterocyclic steroidal systems, belonging mainly to the oestratriene series, has appeared recently. A first approach (Scheme 13), based on the Torgov carbocyclic synthesis, " uses appropriate... 

A flexible method uses the condensation of suitable dienamine systems with appropriate aromatic derivatives. This is illustrated in the reaction of the dienamine (168) with the salt (169), yielding the heterocyclic steroid (170), which is then reduced to its tetrahydro-derivative (171). ... 

The total synthesis of various other heterocyclic steroids, including 13-aza-18-norequilenin (179) and 13-aza-15-thia-18-norequilenin (180), has been achieved. For instance, compound (180) has been prepared through a Bisehler-Napieralski cyelization of a JV-formyl-2-(l-naphthyl)ethylamine, followed by reaction with mercaptoacetic acid. ... 

In addition, some detailed papers have been published on the synthesis of various other specific heterocyclic steroids, as well as on the stereochemical assignments of various configurational isomers of 8-azoestrone. ... 

Heterocyclic steroids. 2,3-Seco-5a-cholestane-2,3-dioic acid (1) is converted into the anhydride (2) in high yield by DCC in dioxane at room temperature. ... 

Miscellaneous Heterocyclic Steroids.—I3-Aza-15-thia-I8-norequilenin, 11-oxo-15,l6-diaza-equilenin, and 18-nor-equilenin analogues as well as ring-A-furan, oxazine, and oxazole analogues of equilenin have been synthesised. The preparation of the thiadiaza-steroids (481) has also been briefly reported. 

---