Variants of the complete synthesis of d,l-19-nortestosterone, d,l-19-norandrost-4-ene-3, 17-dione, and their stereoisomers

Summary The complete synthesis of d,l-19-nortestosterone (I) and its 8-iso- and 9, 10-iso- stereoisomers, and also the synthesis of d,l-19-norandrosten-4-ene-3, 17-dione (VI) and its 9, 10-iso-stereoisomer (IX), has been carried out.The stereodirectivity of the simultaneous reduction of the ⁸⁽⁹⁾ double bond and the aromatic ring conjugated with it by means of alkali metals and alcohol in liquid ammonia, both under Birch's conditions and Wilds and Nelson's conditions, depends on the nature of the substituent at C₁₇; in the case of the 17-ketone (III) and the carbinol (VIII), considerable amounts of the 9- isomers are formed.Compounds (I), (Ia), (Ib), (V), and (VI) possess anabolic activity, but to a smaller extent than the analogous compounds in the d,l-D-homo series.Khimiya Prirodnykh Soedinenii, Vol. 1, No. 3, pp. 180–188, 1965     

C(10)-C(19) bond cleavage reaction of 19-oxygenated androst-4-ene-3,6-dione steroids under various conditions

C(10)-C(19) bond cleavage reaction of 19-hydroxy- and 19-oxoandrost-4-ene-3,6,17-triones (5, 6) was explored under various conditions. Treatment of steroids 5 and 6 with KOH in MeOH gave the A-ring aromatized product 6-oxoestrone (11) in a fair yield, respectively, in contrast, the treatment with a weak base yielded 4-methyl steroid 17 (20%) in the case of 19-alcohol 5 or 19-nor-Delta(5(10))-steroid 9 (12-67%) along with compound 11 (6-27%) in the case of 19-aldehyde 6. Reaction of compound 6 with HCl in MeOH produced 3-methyl ethers of 6-oxoestrone and Delta(6)-estrone, compounds 12 and 14 (ca. 20% each). Thus, 6-oxosteroids 5 and 6 showed unique C(10)-C(19) bond cleavage reactions with a base or acid.     

The mechanism of base-promoted HF elimination from 4-fluoro-4-(4'-nitrophenyl)butan-2-one: a multiple isotope effect study including the leaving group (18)F/(19)F KIE.

Leaving-group fluorine as well as the primary and secondary deuterium kinetic isotope effects (KIEs) have been determined for the base-promoted elimination of hydrogen fluoride from 4-fluoro-4-(4'-nitrophenyl)butan-2-one in aqueous solution. The elimination was studied for formate, acetate, and imidazole as the catalyzing base. The fluorine KIEs were determined using the accelerator-produced short-lived radionuclide (18)F in combination with natural (19)F. The (19)F substrate was labeled with (14)C in a remote position to enable radioactivity measurement of both isotopic substrates. The elimination reaction exhibits large primary deuterium KIEs: 3.2, 3.7, and 7.5 for formate, acetate, and imidazole, respectively, thus excluding the E1 mechanism. The corresponding C(4)-secondary deuterium KIEs are 1.038, 1.050 and 1.014 and the leaving group fluorine KIEs are 1.0037, 1.0047 and 1.0013, respectively. The size of the fluorine KIEs corresponds to 5-15% of the estimated maximum of 1.03 for complete C-F bond breakage. No H/D exchange is observed during the reaction. The size and trends of the KIEs for the different bases are consistent with an E1cB-like E2 or an E1cB(ip) mechanism.     

Synthesis, characterization, and biological activities of some transition metal(II) complexes with the thiosemicarbazone derived from 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one

A new 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one thiosemicarbazone (HL) was synthesized derived from 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one. Four transition metal(II) complexes of HL have been prepared. Elemental analysis, molar conductivity, IR, UV, ¹H NMR spectra, and TG-DTA have been used to characterize these complexes. The complexes have the general formula ML₂, where M = Zn, Cu, Co, and Ni. The ligand and its complexes have been studied for their possible biological activity including anti-inflammatory, antibacterial, and antitumour activity in vitro.     

Conformationally locked heterocycles. Structure of a doubly bridged pyrimido[1,2-a]pyrimidine from the hantzsch synthesis with 4-(2-hydroxyphenyl)but-3-en-2-one

1D and 2D nmr spectroscopy was used to assign the structure to the minor product from cyclocondensation of 4-(2-hydroxyphenyl)but-3-en-2-one with cyanamide, which was identified as (6R*, 9R*, 15R*, 17R*)-6,9-dimethyl-6,17:9,15-dimemano-6H,15H,17H-[1,3,5]benzoxadiazocino[4,5-d][1,3,5]benzoxadiazocine-7(9H)-carbonitrile, a doubly oxygen-bridged pyrimido[1,2-a]pyrimidine derivative. The observed stereose lectivity and reaction mechanisms are discussed with the help of molecular mechanics and semi-empirical PM3 calculations.     

Chemical properties of marine terpenoids. 1. Some reactions of (6S,10R)-10-bromo-3,11,11-trimethyl-7-methylidenespiro[5,5]undec-2-en-4-one,a sesquiterpenoid from the sea hare Aplysia dactylomela

The structures of products obtained by reductive debromination and CF₃COOH- and KOH-induced transformations of natural chamigrane-type sesquiterpenoid (6S,10R)-10-bromo-3,11,11-trimethyl-7-methylidenespiro[5,5]undec-2-en-4-one (dactylone) isolated from the sea hare Aplysia dactylomela were analyzed. The absolute configurations of the reaction products were established by CD spectra taking into account the configuration of the starting dactylone.     

Structural resolution of the stereochemistry of a spirooxirane derived from an α-arylidene heterocyclic carbonyl. The crystal and molecular structure of 2-(p-chlorophenyl)-5-phenyl-7-methyl-1-oxa-5,6-diazaspiro[2.4]hept-6-en-4-one

The stereochemical assignment of molecular geometry for α-arylidene carbonyl compounds and spirooxirane derived from them have continued to be a challenging problem for which the most satisfactory solution continues to be an x-ray diffraction structure determination. In that regard, the title compound (a spirooxirane) has been found to crystallize in the monoclinic space group P2_1/c with cell dimensions of a = 5.989(1)Å, b = 27.625(4)Å, c = 9.374(2)Å, β = 99.06(1)°. The structure of the compound has been determined, with the refinement to R = 0.059. The previous, tentative assignment of structure has been confirmed substantiating our prediction that the oxidation of the enone system proceeds with rotation of the phenyl group on the β-carbon away from the carbonyl group, minimizing adverse steric interactions and allowing orbitals of the carbonyl group to overlap with those of the carbanionic center during the closure of the oxirane ring. The agreement between predictions based on nmr data and the x-ray diffraction determination will support a stronger reliance on the nmr data predictions in subsequent studies.