20‐Hydroxy­imino‐5α‐pregna‐9(11),16‐dien‐3β‐yl acetate and 17‐oxo‐5α‐androst‐9(11)‐en‐3β‐yl acetate

In the title compounds, C₂₃H₃₃NO₃ and C₂₁H₃₀O₃, respectively, the ester linkage in ring A is equatorial. In these steroids, the six‐membered rings A and B have chair conformations, but ring C can be better described as a half‐chair. The five‐membered ring D adopts a 14α‐envelop conformation. The A/B, B/C and C/D ring junctions are trans.     

17‐Oxo‐5α‐androst‐6‐en‐3β‐yl acetate

In the title compound, C₂₁H₃₀O₃, a potential inhibitor of aromatase, all rings are fused trans. Rings A and C have chair conformations which are slightly flattened, whereas the conformation of ring B is close to a half‐chair. Ring D has a 14α‐envelope conformation. The steroid nucleus has a small twist, as shown by the C19—C10⋯C13—C18 (steroid numbering) torsion angle of −6.9 (3)°. Ab initio calculations of the equilibrium geometry of the mol­ecule reproduce this small twist, which appears to be due to the conformation of ring B rather than to packing effects.     

16α,17α‐Epoxy‐20‐oxopregn‐5‐en‐3β‐yl acetate

The title compound, C₂₃H₃₂O₄, has a 3β configuration, with the epoxy O atom at 16α,17α. Rings A and C have slightly distorted chair conformations. Because of the presence of the C5=C6 double bond, ring B assumes an 8β,9α‐half‐chair conformation slightly distorted towards an 8β‐sofa. Ring D has a conformation close to a 14α‐envelope. The acetoxy and acetyl substituents are twisted with respect to the average molecular plane of the steroid. The conformation of the mol­ecule is compared with that given by a quantum chemistry calculation using the RHF–AM1 (RHF = Roothaan Hartree–Fock) Hamiltonian model. Cohesion of the crystal can be attributed to van der Waals interactions and weak intermolecular C—H?O interactions, which link the mol­ecules head‐to‐tail along [101].     

6β‐Azido‐7α‐hydroxy‐17‐oxo‐5α‐androstan‐3β‐yl acetate

In the title compound, C₂₁H₃₁N₃O₄, a potential inhibitor of aromatase, all rings are fused trans. Rings A, B and C have chair conformations which are slightly flattened. Ring D has a 14α‐envelope conformation. The steroid nucleus has a small twist, as shown by the C19—C10⋯C13—C18 torsion angle of 6.6 (2)°. Ab initio calculations of the equilibrium geometry of the mol­ecule reproduce this small twist, which appears to be due to the steric effect of the 6β‐azide substituent rather than to packing effects.     

6β‐Hydroxy‐5β‐methyl‐20‐oxo‐19‐norpregn‐9(10)‐en‐3β‐yl acetate

In the title compound, C₂₃H₃₄O₄, which is an intermediate in the synthesis of pregnane derivatives with a modified skeleton that show potent abortion‐inducing activity, the conformation of ring B is close to half‐chair due to the presence of both the C=C double bond and the axial 5β‐methyl group. Rings A and C have conformations close to chair, while ring D has a twisted conformation around the bridgehead C—C bond. Molecules are hydrogen bonded via the hydroxyl and acetoxy groups into infinite chains. Quantum‐mechanical ab initio Roothan Hartree–Fock calculations show that crystal packing might be responsible for the low values of the angles between rings A and B, and between ring A and rings C and D, as well as for a different steric position of the methyl ketone side chain compared to the geometry of the free molecule.     

3β‐Acetoxy‐5α,6β‐di­hydroxybisnorcholanic acid 2216 lactone

In the title compound, C₂₄H₃₆O₆, the ester linkage in ring A is equatorial. The six‐membered rings A, B and C have chair conformations. The five‐membered ring D adopts a 13β,14α‐half‐chair conformation and the E ring adopts an envelope conformation. The A/B, B/C and C/D ring junctions are trans, whereas the D/E junction is cis.     

3β,7α,12α‐Tri­formyl­oxy‐24‐nor‐5β‐chol‐22‐ene

The title compound, alternatively called 24‐nor‐5β‐chol‐22‐ene‐3β,7α,12α‐triyl triformate, C₂₆H₃₈O₆, has a cis junction between two of the six‐membered rings. All three of the six‐membered rings have chair conformations that are slightly flattened and the five‐membered ring has a 13β,14α‐half‐chair conformation. The 3β, 7α and 12α ring substituents are axial and the 17β group is equatorial. The 3β‐formyl­oxy group is involved in one weak intermol­ecular C—H⋯O bond, which links the mol­ecules into dimers in a head‐to‐head fashion.     

Conformation of 17‐chloro‐16‐formylandrosta‐5,16‐dien‐3β‐yl acetate and 17‐chloroandrosta‐5,16‐dien‐3β‐yl acetate

In the title compounds, C₂₂H₂₉ClO₃, (I), and C₂₁H₂₉ClO₂, (II), respectively, the B rings adopt a half‐chair conformation and the D rings adopt an envelope conformation. A twist of the steroid skeleton of both compounds is observed. There is a positional disorder of the acetoxy group of (II), with the terminal atoms disordered over two positions with near equal occupancy. Quantum‐mechanical ab initio calculations using a molecular orbital Hartree–Fock method were performed for the isolated molecules, thus allowing the distinction within the structural features of these two androstane derivatives of which characteristics are intrinsic to the molecules and which are due to packing effects. The skeletal twisting was found to be innate to the molecules, while the acetoxy disorder is due to packing effects.     

Triterpenoide. XX. 3β‐Acetoxy‐12‐oxo‐18β‐olean‐ und 3β‐Acetoxy‐12,19‐dioxo‐9(11),13(18)‐oleandien‐28‐säure‐methyl­ester

The structures of methyl 3β‐acetoxy‐12‐oxo‐18β‐olean‐28‐oate [C₃₃H₅₂O₅, (I)] and methyl 3β‐acetoxy‐12,19‐dioxoolean‐9(11),13(18)‐dien‐28‐oate [C₃₃H₄₆O₆, (II)] are described. In (I), all rings are in the chair conformation, rings D and E are cis and the other rings trans‐fused. In compound (II), only rings A and E are in the chair conformation, ring B has a distorted chair conformation, ring C a distorted half‐boat and ring D an insignificantly distorted half‐chair conformation.     

16‐(4‐Cyanobenzylidene)‐3β‐pyrrolidinoandrost‐5‐en‐17β‐ol monohydrate

In the title compound, C₃₁H₄₀N₂O·H₂O, the outer two six‐membered rings are in chair conformations, while the central ring is in an 8β,9α‐half‐chair conformation. The five‐membered ring adopts a 13β‐envelope conformation and the cyano­benzyl­idene moiety has an E configuration with respect to the hydroxyl group at position 17. The steroid nuclei are linked by intermolecular O—H?O and O—H?N hydrogen bonds to form a molecular network. The molecular packing has an interesting feature, with the steroids aligned parallel to the b axis, forming a closed loop through hydrogen bonds linked via water mol­ecules.     

16‐[3‐Methoxy‐4‐(2‐piperidin‐1‐yl­ethoxy)­benzyl­idene]‐17‐oxoandrost‐5‐en‐3β‐yl acetate monohydrate

The title compound, C₃₆H₄₉NO₅·H₂O, has the outer two six‐membered rings of the steroid nucleus in chair conformations. The central ring B of the steroid nucleus is in an 8β,9α‐half‐chair conformation, while ring D of the steroid adopts a slightly distorted 13β,14α‐half‐chair conformation. The piperidine ring is in a chair conformation. The methoxy­benzyl­idene moiety has an E configuration with respect to the carbonyl group at position 17. Intermolecular O—H?O and O—H?N hydrogen bonds link the steroid and water mol­ecules into chains which run parallel to the b axis.     

4,6‐Dimethyl‐2‐[(4‐phenylpiperidin‐1‐yl)methyl]isothiazolo[5,4‐b]pyridin‐3(2H)‐one and 4,6‐dimethyl‐2‐[(4‐phenyl‐1,2,3,6‐tetrahydropyridin‐1‐yl)methyl]isothiazolo[5,4‐b]pyridin‐3(2H)‐one

In the crystal structures of the title compounds, C₂₀H₂₃N₃OS, (II), and C₂₀H₂₁N₃OS, (III), significant differences occur in the conformation of, respectively, the phenylpiperidine and phenyltetrahydropyridine substituents at the 2‐position of the isothiazolopyridine system. The piperidine ring adopts a chair conformation, while the tetrahydropyridine ring assumes a half‐chair form. The phenylpiperidine and phenyltetrahydropyridine fragments exhibit different conformations resulting from the steric and conjugation effects in the phenyl ring, respectively. Theoretical calculations show that both conformations are energetically stable and correspond to a minimum of energy for the analyzed systems. The molecular packing in (II) is influenced by π–π interactions of the isothiazolopyridine systems, with a shortest centroid‐to‐centroid separation of 3.5843 (11) Å between pyridine rings. In the crystal structure of (III), the molecules are linked by C—H...O hydrogen bonds and C—H...π interactions.     

5β,6β‐Epoxy‐17‐oxoandrostan‐3β‐yl acetate and 5β,6β‐epoxy‐20‐oxopregnan‐3β‐yl acetate

In the title compounds, C₂₁H₃₀O₄, (I), and C₂₃H₃₄O₄, (II), respectively, which are valuable intermediates in the synthesis of important steroid derivatives, rings A and B are cis‐(5β,10β)‐fused. The two molecules have similar conformations of rings A, B and C. The presence of the 5β,6β‐epoxide group induces a significant twist of the steroid nucleus and a strong flattening of the B ring. The different C17 substituents result in different conformations for ring D. Cohesion of the molecular packing is achieved in both compounds only by weak intermolecular interactions. The geometries of the molecules in the crystalline environment are compared with those of the free molecules as given by ab initio Roothan Hartree–Fock calculations. We show in this work that quantum mechanical ab initio methods reproduce well the details of the conformation of these molecules, including a large twist of the steroid nucleus. The calculated twist values are comparable, but are larger than the observed values, indicating a possible small effect of the crystal packing on the twist angles.     

Octa‐O‐acetyl‐β,β‐thiotrehalose

The structure of the title compound, C₂₈H₃₈O₁₈S, has been determined. The torsion angles of the glycosidic linkage in the non‐reducing disaccharide, ?_H and ?_H′, have values of 3 and 53°, respectively. The latter torsion angle is in agreement with the exo‐anomeric effect, whereas the former shows an eclipsed conformation. Both glyco­pyran­osyl residues adopt a slightly distorted chair conformation.     

3β‐(1‐Allyl‐1‐pyrrolidinio)‐16‐(2‐pyridylmethylene)androst‐5‐en‐17β‐ol bromide hemihydrate

The title compound, C₃₂H₄₅N₂O⁺·Br^?·0.5H₂O, has the outer two six‐membered rings in chair conformations, while the central ring is in an 8β,9α‐half‐chair conformation. The five‐mem­bered ring of the steroid nucleus adopts a slightly deformed 14α‐envelope conformation. The pyridyl­methyl­ene moiety has an E configuration with respect to the hydroxyl group at position 17. The structure is stabilized by a network of O—H?Br‐type intermolecular hydrogen bonds.     

16‐(4‐Cyano­benzyl­idene)‐17‐oxo­androst‐5‐en‐3β‐ol

In the title compound, 4‐(3β‐hydroxy‐17‐oxoandrost‐5‐en‐16‐ylidenemethyl)benzonitrile, C₂₇H₃₁NO₂, rings A and C of the steroid nucleus are in chair conformations. The central six‐membered ring B is in an 8β,9α‐half‐chair conformation, while the five‐membered ring D adopts a 13β,14α‐half‐chair conformation. The cyano­benzyl­idene moiety has an E configuration with respect to the carbonyl group at position C17. The dihedral angle between the planes of the steroid nucleus and the cyano­benzyl­idene moiety is 22.61 (15)°. Intermolecular O—H⃛N hydrogen bonds formed between the hydroxyl group of the steroid and the N atom of the cyano­benzyl­idene moiety of symmetry‐related mol­ecules link the steroid mol­ecules into chains which run parallel to the b axis.     

17‐Oxo‐16‐(2‐pyridyl­methyl­ene)­androst‐5‐en‐3β‐ol monohydrate

The title compound, C₂₅H₃₁NO₂·H₂O, has the outer two six‐membered rings in chair conformations, while the central ring is in an 8β,9α‐half‐chair conformation. The five‐membered ring adopts a 13,14‐half‐chair conformation. The pyridyl­methyl­ene moiety has an E configuration with respect to the carbonyl group at position 17. The structure is stabilized by intermolecular O—H?N and O—H?O hydrogen bonds.     

Powder X‐ray study of racemic (2RS,3RS)‐5‐amino‐3‐[4‐(3‐methoxyphenyl)piperazin‐1‐yl]‐1,2,3,4‐tetrahydronaphthalen‐2‐ol

The structure of the title benzovesamicol analogue, C₂₁H₂₇N₃O₂, an important compound for the diagnosis of Alzheimer's disease, has been determined by X‐ray powder diffraction. The title compound was firstly synthesized and characterized by spectroscopic methods (FT–IR, and ¹³C and ¹H NMR). The compound is a racemic mixture of enantiomers which crystallizes in the monoclinic system in a centrosymmetric space group (P2₁/c). Crystallography, in particular powder X‐ray diffraction, was pivotal in revealing that the enantio‐resolution did not succeed. The piperazine ring is in a chair conformation, while the cyclohexene ring assumes a half‐chair conformation. The crystal packing is dominated by intermolecular O—H...N hydrogen bonding which links molecules along the c direction.     

Powder X‐ray study of racemic (2RS,3RS)‐5‐amino‐3‐(4‐phenylpiperazin‐1‐yl)‐1,2,3,4‐tetrahydronaphthalen‐2‐ol

The title compound, C₂₀H₂₅N₃O, an important precursor for the preparation of benzovesamicol analogues for the diagnosis of Alzheimer's disease, has been synthesized and characterized by FT–IR, and ¹H and ¹³C NMR spectroscopic analyses. The crystal structure was analysed using powder diffraction as no suitable single crystal was obtained. The piperazine ring has a chair conformation, while the cyclohexene ring assumes a half‐chair conformation. The crystal packing is mediated by weak contacts, principally by complementary intermolecular N—H...O hydrogen bonds that connect successive molecules into a chain. Further stabilization is provided by weak C—H...N contacts and by a weak intermolecular C—H...π interaction.     

Oxidative Fragmentations of the 5α‐ and 5β‐Hydroxy‐B‐norcholestan‐ 3β‐yl Acetates

Oxidations of 5α‐hydroxy‐B‐norcholestan‐3β‐yl acetate ( 8 ) with Pb(OAc)₄ under thermal or photolytic conditions or in the presence of iodine afforded only complex mixtures of compounds. However, the HgO/I₂ version of the hypoiodite reaction gave as the primary products the stereoisomeric (Z)‐ and (E)‐1(10)‐unsaturated 5,10‐seco B‐nor‐derivatives 10 and 11 , and the stereoisomeric (5R,10R)‐ and (5S,10S)‐acetals 14 and 15 (Scheme 4). Further reaction of these compounds under conditions of their formation afforded, in addition, the A‐nor 1,5‐cyclization products 13 and 16 (from 10 ) and 12 (from 11 ) (see also Scheme 6) and the 6‐iodo‐5,6‐secolactones 17 and 19 (from 14 and 15 , resp.) and 4‐iodo‐4,5‐secolactone 18 (from 15 ) (see also Scheme 7). Oxidations of 5β‐hydroxy‐B‐norcholestan‐3β‐yl acetate ( 9 ) with both hypoiodite‐forming reagents (Pb(OAc)₄/I₂ and HgO/I₂) proceeded similarly to the HgO/I₂ reaction of the corresponding 5α‐hydroxy analogue 8 . Photolytic Pb(OAc)₄ oxidation of 9 afforded, in addition to the (Z)‐ and (E)‐5,10‐seco 1(10)‐unsaturated ketones 10 and 11 , their isomeric 5,10‐seco 10(19)‐unsaturated ketone 22 , the acetal 5‐acetate 21 , and 5β,19‐epoxy derivative 23 (Scheme 9). Exceptionally, in the thermal Pb(OAc)₄ oxidation of 9 , the 5,10‐seco ketones 10, 11 , and 22 were not formed, the only reaction being the stereoselective formation of the 5,10‐ethers with the β‐oriented epoxy bridge, i.e. the (10R)‐enol ether 20 and (5S,10R)‐acetal 5‐acetate 21 (Scheme 8). Possible mechanistic interpretations of the above transformations are discussed.