L. C. R. Andrade

X-ray and deuterium labeling studies on the abnormal ring cleavages of a 5β-epoxide precursor of formestane

A new convergent synthesis of the antitumor steroid formestane (4-OHA) 5 has been performed from the easily available epimeric mixture of 5 alpha- and 5 beta-androst-3-en-17-one 1a and 1b in order to attempt a yield improvement. A two-step oxidative route followed by base-catalyzed isomerization was applied to the 5 alpha- and 5 beta-epimers 1a and 1b, either as a mixture or separately, leading to the title compound 5. From epimer 1a an efficient process was attained to prepare the desired aromatase inhibitor formestane. Epimer 1b led to the formation of the same compound 5. Additionally, 1b have also been converted in 5 beta-hydroxyandrostane-3,17-dione 12 and androst-4-ene-3,17-dione 13, revealing an unexpected reactivity of the 3 beta,4 beta-epoxy-5 beta-androstan-17-one intermediate 6 formed from 1b during the first oxidative step with performic acid. Cleavage of the epoxide 6 led to the trans-diaxial and the trans-diequatorial vic-diols 7 and 8 and to the 1,3-diol 9. The formation of the abnormal products 8 and 9 were investigated through X-ray and deuterium labeling studies. Diol 8 was formed through a trans-diequatorial epoxide ring opening and the 1,3-diol 9 was formed through an intramolecular rearrangement involving a 1,2-hydride shift. All the vic-diols 3, 7 and 8 formed, proved to be good precursors for the synthesis of the target compound 5.

Local order in concentrated aqueous solutions of yttrium chloride and bromide

X-ray diffraction patterns of equimolecular concentrated aqueous solutions of yttrium chloride and bromide have been investigated from s=0.4 AA-1 up to s=15 AA-1. An assumed coordination of eight water molecules around each yttrium cation, at a distance of 2.36 AA, reproduces the intensity at high s values in agreement with the values obtained by some of the present authors from EXAFS experiments. Narrow interference maxima at s=(4 pi sin theta )/ lambda approximately=0.9 AA-1 may be interpreted as the existence of a local order of the hydrated yttrium cations surrounded by anions and free water molecules. Structural models with and without close packing of the hydrated cations were built to simulate that local order.

Charge densities of two rutile structures: NiF2 and CoF2

X-ray diffraction data were collected at room temperature for two rutile structures, NiF 2 and CoF 2 . Two different crystals of each compound have been used in the experiments. Atomic and thermal parameters were derived from least-squares refinements of high-angle data [(sinθ)λ≥0.6 A -1 ]. The results of Fourier inversion of the differences between observed and model structure factors are presented and discussed in terms of difference density maps

3β,5α,6β-Trihy­droxy­androstan-17-one

The title compound, C19H30O4, is an androstan-17-one derivative synthesized from the dehydroepiandrosterone through a sequential addition of an oxidant, followed by a trans-diaxial opening of the epoxide generated, with Bi(OTf)3 (OTf is trifluoromethanesulfonate). The six-membered rings have a slightly flattened chair conformation, while the five-membered ring adopts a 14-α envelope conformation. All rings are trans fused. In the crystal, the molecules are connected by O—H⋯O hydrogen bonds involving the hydroxyl and carbonyl groups, forming a three-dimensional network. A quantum mechanical ab initio Roothan Hartree–Fock calculation of the free molecule gives bond lengths, valency angles and ring torsion angles of the free molecule at equilibrium geometry (energy minimum) close to the experimental values.

Androstane-3β,5α,6β,17β-tetrol tri-hydrate.

The title hydrated tetrol, C19H32O4·3H2O, was synthesized by stereoselective reduction of the compound 3β,5α,6β-trihydroxyandrostan-17-one. All rings are fused trans. The organic molecules are connected head-to-tail along the c axis via O—H⋯O hydrogen bonds. Layers of water molecules in the ab plane interconnect these chains. A quantum chemical ab initio Roothan Hartree–Fock calculation of the isolated molecule gives values for the molecular geometry close to experimentally determined ones, apart from the C—O bond lengths, whose calculated values are significantly smaller than the measured ones, probably a consequence of the involvement of the C—OH groups in the hydrogen-bonding network.

6-[(4-Fluorophenyl)(1H-imidazol-1-yl)methyl]-1,3-benzodioxol-5-ol and 6-[(4-methoxyphenyl)(1H-imidazol-1-yl)methyl]-1,3-benzodioxol-5-ol.

The title compounds, C(17)H(13)FN(2)O(3) and C(18)H(16)N(2)O(4), are new potent aromatase inhibitors combining the common features of second- and third-generation nonsteroid anti-aromatase compounds. The molecules have a propeller shape, with dihedral angles between adjacent planes in the range 49-86°. A quantum mechanical ab initio Roothaan-Hartree-Fock calculation for the isolated molecules shows values for these angles close to the ideal value of 90°. Docking studies of the molecules in the aromatase substrate show that their strong inhibitor potency can be attributed to molecular flexibility, hydrophobic interactions, heme Fe coordination and hydrogen bonding.

3α,4α-Ep­oxy-5α-androstan-17β-yl acetate

The title compound, C21H32O3, results from modifications of the A and D rings of the aromatase substrate androstenedione. Ring A adopts a conformation between 10β-sofa and 1α,10β half-chair. Rings B and C are in slightly flattened chair conformations. Ring D approaches a 13β-envelope conformation, probably due to the acetoxy substituent, and shows a very short Csp 3—Csp 3 bond next to the epoxide ring, which is characteristic of 3–4 epoxides. .

Cyanosilylation at pregnane side-chains. Selective synthesis and crystal structure of 20(R)-silylated cyanohydrins.

Trimethylsilylcyanide addition to different carbonyl moieties, i.e. saturated ketones, an enone and an aldehyde, at the steroid side-chain, was studied in the presence of a convenient catalyst. Depending on the nature of the carbonyl group, different outcomes were noticed. Saturated 20-keto pregnanes yielded epimerically pure silylated cyanohydrins, being the absolute configuration unambiguously established by X-ray crystallographic analysis.

17-Oxo-5α-androstane-3α, 4β-diyl diacetate and 17-oxo-5β-androstane-3α, 4β-diyl diacetate

The title compounds, both C23H34O5, are the 5alpha and 5beta configurations of two diacetate epimers. The 5beta-diacetate crystallizes in an hexagonal structure, unusual for steroid molecules. The unit cell has an accessible solvent volume of 358 A(3), responsible for clathrate behaviour. The 5beta-epimer also features some shorter than average bond lengths in the 3alpha,4beta-acetoxy groups. The conformations of the molecules of both epimers are compared with those obtained through ab initio quantum chemistry calculations. Cohesion of the crystals can be attributed to van der Waals and weak molecular C-H...O interactions.

X‐Ray Study of Mixed Compounds of Betaine Arsenate and Deuterated Betaine Arsenate

Accurate X-ray diffraction measurements were carried out in a series of powdered mixed compounds (BA) 1-x (DBA) x , The behaviour of the lattice parameters a, b, c and β as a function of x were analyzed. The behaviour of the lattice parameters as a function of temperature provided evidence for different phase transitions in BA and DBA92 and pointed out the existence of a strong anisotropy in these systems.