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Biotinylated 17β-estradiol (E2) derivatives are helpful probes for a better understanding of biospecific E2 interactions with steroid-binding proteins such as the estrogen receptor and anti-steroid antibodies. We describe synthetic strategies for the biotinylation of E2 toward the 3, 6α, and 7α positions using biotinyl-N-hydroxysuccinimide esters with different spacers, varying in structure and chain length. Key reaction for biotinylation at the 3 position is the regioselective ether formation of the phenolate E2 anion with a linker mesylate without protecting the 17β-hydroxyl group. The 6α position is accessible via a 3,17β protected 6α-hydroxy E2, prepared by stereospecific sodium borohydride reduction of 6-oxo E2. Direct cyanoethylation of the alcohol followed by reduction to the amine allows the biotinylation to 6α-O-coupled cyanoethyloxy linker E2 derivatives. Alternatively, 6α-O-coupled cyanoalkyloxy polyether linker E2 probes are obtained by a Williamson ether synthesis of the alcohol precursor with ω-t-butyl-dimethylsilyloxy-5-oxa-nonylmesylate. Cyanoethylation of the desilylated compound and further reduction of the nitrile led to the terminal amine. Reductive amination of the 3,17β acetylated 6-oxo E2 compound with 6-cyanoethyloxyhexyl ammonium acetate yields in a mixture of 6α/β-N-alkylated E2 nitriles. The epimers are separated by reversed-phase HPLC and the 6α-compound subsequently reduced to the terminal amine. The 7α-biotinylated E2 compound is derived from 7α-(11‘-undecyl-N-methyl-N-butylamide) E2, which is already known from literature. Subsequently, the 3 and 17β positions are protected, and the amide is reduced to the 7α-(11‘-undecanol) compound. Further cyanoethylation and reduction led to the 11‘-amino-ethyloxyundecyl E2. Using ¹H NMR analysis, it could be shown that the biotin moiety of the biotinylated 6α- and 7α-E2 derivatives has an axial position which results in a vertical orientation of the substituent toward the α-face of the planar tetracyclic backbone. Thus, a negligible alteration of the original structure of the upper β-face offers the feasibility of applying the 6α- and 7α-derivatives as optimal tracers in competitive immunoassays.

The crystal structure of philolithite, Pb12O6Mn(Mg,Mn)2(Mn,Mg)4(SO4)(CO3)4Cl4(OH)12, P42/nnm, a = 12.627(9), c = 12.595(9) Å, V = 2008(2) Å3, Z = 2 has been solved by Patterson difference- Fourier syntheses and refined to R = 0.053 for 814 Fo > 4σFousing MoKα X-ray data. In the structure, MnO6octahedra form straight chains parallel to [110] and [11̅ 0] by sharing opposite octahedral edges. Octahedra within the chains are further linked by sharing free corners with MnO4and SO4tetrahedra and CO3triangles. The MnO4and SO4tetrahedra also form bridging struts between octahedral chains, connecting them in the [001] direction into an open framework. The Pb, Cl, and nonframework O atoms occupy the open spaces within the framework. The 10- and 12-fold coordinations of the Pb atoms exhibit the lone-pair effect. Pb atoms link via short bonds to non-framework O atoms to form chains parallel to [110] and [ 1̅10]. When viewed down [111], [ 1̅1̅̅ 1], [1̅1̅̅1], or [11̅1̅̅], [ 1̅11̅] the framework (less the CO3groups) is seen to be based upon cubic closest-packing of anions. This open framework of composition [[6](Mn,Mg)122+[4](SO4)22-[4](Mn2+O4)6-2O8(OH)24]32-, referred to as a closestpacked trellis, is the fundamental unit for the structure.

The crystal structure of philolithite, Pb12O6Mn(Mg,Mn)2(Mn,Mg)4(SO4)(CO3)4Cl4(OH)12, P42/nnm, a = 12.627(9), c = 12.595(9) Å, V = 2008(2) Å3, Z = 2 has been solved by Patterson difference- Fourier syntheses and refined to R = 0.053 for 814 Fo > 4σFousing MoKα X-ray data. In the structure, MnO6octahedra form straight chains parallel to [110] and [11̅ 0] by sharing opposite octahedral edges. Octahedra within the chains are further linked by sharing free corners with MnO4and SO4tetrahedra and CO3triangles. The MnO4and SO4tetrahedra also form bridging struts between octahedral chains, connecting them in the [001] direction into an open framework. The Pb, Cl, and nonframework O atoms occupy the open spaces within the framework. The 10- and 12-fold coordinations of the Pb atoms exhibit the lone-pair effect. Pb atoms link via short bonds to non-framework O atoms to form chains parallel to [110] and [ 1̅10]. When viewed down [111], [ 1̅1̅̅ 1], [1̅1̅̅1], or [11̅1̅̅], [ 1̅11̅] the framework (less the CO3groups) is seen to be based upon cubic closest-packing of anions. This open framework of composition [[6](Mn,Mg)122+[4](SO4)22-[4](Mn2+O4)6-2O8(OH)24]32-, referred to as a closestpacked trellis, is the fundamental unit for the structure.

We describe synthetic strategies for the biotinylation of testosterone (T) at positions 3, 7α, 17α, and 19. These T probes are able to mimic ligand binding and may provide for a better understanding of the biospecific interaction with steroid-binding proteins such as the androgen receptor, anti-steroid antibodies, or steroid-binding serum globulins. For the 7α- and 17α-derivatives, biotinyl-N-hydroxy-succinimide esters with different types of spacer chains were used. The 3-biotin hydrazone derivative was produced using N-(ε-biotinyl)-caproyl hydrazide, whereas for the 19-biotinylation, a biotinyl-1-N-diamino-3,6-dioxaoctane-amide was applied. Key reaction for the biotinylation at position 3 is the oximation of the 3-oxo function. The 17α-position is accessible by the reaction of the 3-protected 4-androsten-17-epoxide with oxygen in the β-position, followed by nucleophilic ring opening with cyanide which provides the 17α-cyanomethyl derivative. The key step is the regioselective ketal protection of the 3-oxo function of androst-4-ene-3,17-dione using a stannoxane catalyst. An alternative pathway for the insertion of biotin at the 19-position was established by the synthesis of 17β-hydroxy-androst-4-en-3-one-19-yl carboxymethyl ether. After activation by the carbodiimide method, the compound reacts with aminoterminal biotin derivatives. The copper(I)-catalyzed 1,6 Michael addition of 17-acetoxy-6,7-dehydro-T leads to 7α-derivatives by use of ω-silyl protected hydroxylalkyl-modified Grignard reagents. A functional group interconversion using the Staudinger reaction transforms the azide function into a primary ω-amino group. The absolute configurations of the different biotinylated derivatives were investigated by ¹H NMR studies. For the 7α-biotinylated T series, additionally, an X-ray analysis proved the axial position of the spacer group. This results in a vertical orientation of the biotin moiety toward the α-face of the planar tetracyclic backbone. Thus, a negligible alteration of the original structure of the upper β-face offers the feasibility of applying the 7α-derivatives as optimal immunochemical tracers in competitive immunoassays. Biotinylated T derivatives should be also suitable for ligand-binding studies to the androgen receptor or to sex hormone-binding globulin.

Khmaralite, Ca0.04Mg5.46Fe3+0.12Fe2+1.87Al14.26Be1.43B0.02Si4.80O40, is a new mineral closely related to sapphirine from Khmara Bay, Enderby Land, Antarctica. It occurs in a pegmatite metamorphosed at T ≥ 820 ℃, P ≥ 10 kbar. The minerals surinamite, musgravite, and sillimanite associated with khmaralite at Casey Bay saturate it in BeO, and thus its BeO content could be close to the maximum possible. Optically, khmaralite is biaxial (-); at λ = 589 nm, α = 1.725(2), β = 1.740(2), γ = 1.741(2), 2Vmeas= 34.4 (1.8)°, v > r strong, and β ∥ b. The weak superstructure reported using electron diffraction has been confirmed by single-crystal X-ray diffraction. The superstructure corresponds to a doubling of the a axis in monoclinic sapphirine-2M (P21/c setting) with the following unit-cell parameters: a = 19.800(1), b = 14.371(1), c = 11.254(1) Å, β = 125.53(1)°, Z= 4, Dcalc= 3.61 g/cm3. Using a simplified chemical formula of Mg5.46Al14.28Fe2.00Si4.80Be1.46O40, the fully anisotropic structure refinement of all site occupancies, including Al vs. Mg and Al vs. Si on the 16 octahedral (M) and 12 tetrahedral (T) sites respectively, establishes that the 2×a superstructure results primarily from ordering in the doubled (T1 → T6, T7 → T12) tetrahedral chain, which is parallel to the a axis. The strongest contri­bution comes from Al-Si-Be ordering on the T2 (33-16-51%) vs. T8 (0-95-5%) and T3 (4-78-18%) vs. T9 (30-0-70%) sites. Thus, the sequence Al-Si-Al in sapphirine is replaced by the sequence Si- Be-Si in khmaralite; i.e., Be replaces Si on two sites and Si replaces Al on on four adjacent sites, resulting in an indirect replacement of Al by Be by the coupled substitution Be + Si = 2Al. The Be distribution in khmaralite and the strong preference for Be/Al mixing over Be/Si mixing appear to satisfy the bonding requirements of the bridging O atoms by minimizing the number of Be-O-Be and Be-O-Al linkages.

The regioselective N‐alkylation of the enaminone (I) is achieved using the tosyl esters (II).