Irén Vincze

Inclusion complexes of ketosteroids with β-cyclodextrin

Abstract Inclusion complexes of several steroid derivatives with β-cyclodextrin ( 7 ) were studied in dimethylsulfoxide solution. The investigated molecules were ketosteroids with different functional groups on the skeleton: 3β-acetoxypregn-5-en-20-one ( 1 ), 3β-acetoxypregna-5,16-dien-20-one ( 2 ), 3β-acetoxyandrost-5-en-17-one ( 3 ), 3β-hydroxyandrost-5-en-17-one ( 4 ), 5α-androstane-3,17-dione ( 5 ) and 17β-hydroxyandrost-4-en-3-one ( 6 ). Complex formation was monitored by two-dimensional ROESY experiments through the detection of intermolecular dipolar interactions. In case of inclusion complex formation, the steroid molecule penetrates the cavity of the cyclodextrin and dipole–dipole interactions (ROEs) can be detected between the glucose H-3 and H-5 protons inside the cyclodextrin cavity and the steroid skeletal protons. Intermolecular interactions were detected in all six cases. However, ROESY experiments provided data indicating only partial immersion (A and B ring of the steroid skeleton) in case of 1 , 2 and 6 . On the contrary, compounds 3 and 5 , showing the most correlation rich spectra, seem to fully immerse in the β-cyclodextrin cavity.

Syntheses and advanced NMR structure determination of androsteno-[17,16-d]-pyrimidine derivatives.

Reactions of 16-hydroxymethylene- and 16-aminomethylene-3beta-hydroxy-5-androsten-17-one with formamide and guanidine were carried out resulting in the formation of [16,17-d]-pyrimidine rings. Advanced two-dimensional NMR methods were used to investigate the structure of the products. Homonuclear-, and heteronuclear chemical shift correlation experiments yielded the complete 1H-, 13C- and 15N signal assignment for these compounds.

Steroids 48. Synthesis of 16α-ethyl-21-hydroxy-19-norpregn-4-ene-3,20-dione from 17-substituted 3-methoxyestradiols

Abstract A new synthesis of 16α-ethyl-21-hydroxy-19-norpregn-4-ene-3,20-dione is described, starting from 17-cyano- and 17α-ethynyl-3-methoxyestra-1,3,5(10)-trien-17-ols. (Steroids 58: 185–189, 1993)

Steroids 49. Investigations on the dehydration of 17α-ethynl-17β- hydroxysteroids

The acidic dehydration of 17 alpha-ethynyl-17 beta-hydroxysteroids (1-3) was investigated. On reaction with thionyl chloride, phosphorus oxychloride, and formic acid, the desired dehydration was accompanied by chlorination, Wagner-Meerwein rearrangement, and D-homoaromatic rearrangement. The structure of the product from the transformation of 17 beta-hydroxypregn-20-yne derivative (3) on reaction with formic acid was misjudged. It was regarded as a pregn-16-en-20-yne (10) instead of the actually rearranged D-homoaromatic compound (11). As a consequence, physical data corresponding to this latter structure have been cited in the literature as those of pregn-16-en-20-yne derivative (10). This confusion prompted us to prepare compounds of both types (4, 9, 10, and 11), the characterization of which is here described.

Steroids 54. Amino acylamidosteroids.

Aminosteroids were prepared and acylated with protected amino acids by means of the mixed anhydride or the active ester method. The tert-butyloxycarbonyl- (BOC) protecting group was eliminated by acidolysis, and the benzyloxycarbonyl- (Z) group by catalytic hydrogenation. 3 beta- and 6 beta-Glycylamidosteroids were prepared by indirect amination of chloroacetamido derivatives, formed by the Ritter reaction on the corresponding 3 alpha,5 alpha-cyclo and 5 alpha,6 alpha-epoxy steroids. Water-soluble double salts were produced from the compounds for pharmacological investigations.

The preparation of 2,4-dibromoestra- 1,3,5(10),6-tetraene-3,17 β-diol diacetate

Abstract [ 2,4,6,7 - 3 H 4 ]Estradiol is used for the quantitative determination of estradiol receptors. The synthesis of 2,4-dibromoestra-1,3,5(10),6-tetraene-3,17β-diol 3,17-diacetate, the convenient precursor of [2,4,6,7- 3 H 4 ]estradiol, is described. 6-Alkoxy compounds were also prepared and investigated.

Steroids 51. An improved synthesis of ORG 2058 and the synthesis of [3H]ORG 2058

16 alpha-Ethyl-21-hydroxy-19-norpregn-4-ene-3,20-dione (ORG 2058) is a ligand widely used in progesterone receptor assays. An improved synthesis of the compound is reported, starting from norethisterone acetate. The preparation of the tritiated radioligand [3H]ORG 2058 is also described.