Ring Junction Research Articles

Crystal structure of guggulsterone Z

The crystal structure of the title compound (4,17(20)-trans-pregnadiene-3,16-dione, C21H28O2) has been determined by direct methods using single-crystal X-ray diffraction data. The compound crystallizes into the orthorhombic space group P212121 with the unit cell parameters a = 7.908(2) A, b = 13.611(3) A, c = 16.309(4) A, and Z = 4. The structure has been refined to R = 0.058 for 3667 observed reflections. The bond distances and angles are in good agreement with guggulsterone E and other related steroid molecules. Ring A exists in the distorted sofa conformation, while rings B and C adopt the distorted chair conformation. Five-membered ring D is intermediate between the half-chair and envelope conformations. The A/B ring junction is quasi-trans, while ring systems B/C and C/D are trans fused about the C(8)–C(9) and C(13)–C(14) bonds, respectively. The steroid nucleus has a small twist, as shown by the C(19)–C(10)...C(13)–C(18) pseudo-torsion angle of 7.2°. The crystal structure is stabilized by intra-and intermolecular C-H...O hydrogen bonds.

(2′′S,5′′R,7′′S)-2-[2′-(2′′-Methyl-1′′,6′′-dioxaspiro[4.5]dec-7′′-yl)ethylsulfonyl]-1,3-benzothiazole

The crystal structure of the title compound, C18H23NO4S2, has been investigated in order to establish the relative stereochemistry at the spiro ring junction and the absolute stereochemistry of the mol­ecule. The title compound is a key inter­mediate for the synthesis of the spiro­acetal-containing anti-Helicobacter pylori agent, spiro­laxine methyl ether, for which the absolute stereochemistry has not previously been reported.

Rhodium(I)-Catalyzed Intramolecular Pauson−Khand-Type [2 + 2 + 1] Cycloaddition of Allenenes

[reaction: see text] The novel [RhCl(CO)(2)](2)-catalyzed [2 + 2 + 1] cycloaddition of allenenes leading to the bicyclo[4.3.0]non-1(9)-en-8-one as well as the bicyclo[5.3.0]dec-1(10)-en-9-one skeletons has been developed. This method also provides a new procedure for the construction of the bicyclo[4.3.0]non-1(9)-en-8-one skeleton having an alkyl appendage at the ring juncture, which was hardly attained in a satisfactory yield by the Pauson-Khand reaction of the corresponding enynes.

8′-Methoxy-3H-spiro[1-naphthofuran-2,2′-chroman

The crystal structure of the title compound, C21H18O3, has been determined to establish the relative stereochemistry at the spiro ring junction. Each O atom adjacent to the junction lies axial to the neighbouring ring; this is presumably due to anomeric effects.

Cespitulactones A and B, new diterpenoids from Cespitularia taeniata

Two new diterpenoids, designated cespitulactones A ( 1) and B ( 2), were isolated from a sample of the soft coral Cespitularia taeniata collected in Taiwan. Compound 1 possesses a novel structure with a bond cleavage between C-10 and C-11, and having a 14-membered lactone ring junction between C-10 and C-12. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical derivatization. The isolated compounds were also evaluated for cytotoxicity toward human cancer cell lines.

Crystal structure of 3β-acetoxy-pregna-5,16-dien-20-one (16 DPA)

The title compound, 3β-acetoxy-pregna-5,16-dien-20-one, C23H32O3, has been synthesized by acetylation followed by oxidation of diosgenin and its crystal structure has been solved from single crystal X-ray diffraction data. The compound crystallizes into orthorhombic space group P212121 with unit cell parameters: a = 6.031(4) A, b = 12.481(2) A, c = 27.162(5) A, Z = 4. The crystal structure has been refined to R = 0.0597 for 1291 observed reflections. Rings A and C of the compound are in chair conformation whereas ring B is in half-chair conformation. Ring D is in envelop conformation. The A/B ring junction is quasi-trans, while ring systems B/C and C/D are trans fused about the C8–C9 and C13–C14 bonds, respectively. The steroid nucleus has a small twist, as shown by the C19–C10⋅C13–C18 pseudo-torsion angle of 9.5°. The crystal packing is determined by a pair of weak C–H⋅O hydrogen bonds in addition to van der Waals interactions.

Free radicals formed by H(Mu) addition to triphenylene and dodecahydrotriphenylene

Muonium has been used as an H atom analogue to investigate the free radicals formed by H addition to the fused polyaromatic hydrocarbon triphenylene. Although there are three inequivalent sites of attack in this molecule, only two radicals were detected. Muon and proton hyperfine constants were determined by transverse field μSR and LCR, respectively. With the help of quantum calculations, all the signals can be assigned to radicals formed by Mu addition to C–H sites, while there is no evidence for addition to the tertiary carbons at ring junctions. To force attack on a tertiary carbon, a complementary study was conducted on the dodecahydrotriphenylene molecule. As expected, only one radical is formed. From LCR measurements the number of non-equivalent protons are interpreted as the results of the conformational effect of the saturated side rings.

Crystal Structure of (25R)-Spirost-5-en-3 .BETA.-acetate

(25R)-Spirost-5-en-3 β-acetate (C29H44O4) crystallizes in monoclinic space group P21 with a = 14.559(2), b = 6.212(3), c = 14.847(7)A; β = 100.22(2)°, Z = 2, Dcal = 1.148 Mg/m3. The structure was solved by direct methods and refined by full-matrix least-squares procedures to a final R-value of 0.0513 for 2176 observed reflections. The six-membered A, C and F rings adopt the chair conformation, whereas rings B and D are in the half-chair conformation. Ring E is in the envelope conformation. The A/B ring junction is quasi-trans, while ring junctions B/C and C/D are trans fused about the C8-C9 and C13-C14 bonds, respectively. The D/E ring junction is cis. The molecule is slightly convex towards the β side, with an angle of 10.7(2)°. Cohesion of the molecules in the unit cell can be attributed to van der Waals interactions.

Synthesis of [6,n] cis-fused ring compounds via Cr-mediated dearomatisation–ring-closing metathesis

cis-Fused [6,8], [6,7], [6,6] and [6,5] ring systems containing a cyclohexadiene ring unit, a cycloenone ring and a quaternary carbon at the ring junction were obtained in only two steps from [Cr(CO)3(eta6-p-methoxyphenyl oxazoline)]. The sequence proceeds via diastereoselective addition of three C-substituents across an arene double bond, followed by allylation and ring closing metathesis (RCM). RAMP-hydrazone and (R)-isopropyloxazoline were used as chiral auxiliaries to provide, after removal of the auxiliaries, the enantiomerically highly enriched [6,7] cis-fused system.

Crystal Structure of 6.ALPHA.,7.ALPHA.:24.ALPHA.,25.ALPHA.-Diepoxy-5.ALPHA.,12.ALPHA.-dihydroxy-1-oxo-20S,22R-witha-2-enolide Isolated from Datura quercifolia Leaves

Phytochemical investigations of the Datura quercifolia (Solanaceae) plant yielded a minor withanolide. The structure of the withanolide was established by spectral analysis and X-ray diffraction studies as 6α,7α:24α,25α-diepoxy-5α,12α-dihydroxy-1-oxo-20S,22R-witha-2-enolide (C28H38O7. CH3OH). The withanolide crystallizes in the orthorhombic space group P212121 with unit cell parameters a = 6.916(4), b = 19.199(2), c = 20.138(5)A, Z = 4, Dcal = 1.288 Mg m-3. The crystal structure was solved by direct methods and refined to R = 0.0462 for 1628 observed reflections. The ring conformations are: A and B, half-chair; C, chair; D, intermediate between half-chair and envelope; E, diplanar. The geometry of the rings is trans at the A/B, B/C and C/D ring junctions. The twist along the length of the steroid nucleus is negligible [C19-C10…C13-C18 = 3.3°]. The crystal structure is stabilized by intra- and intermolecular O-H…O and C-H…O hydrogen bonds.

Isolation and Structural Modification of 7-Deoxynarciclasine and 7-Deoxy-trans-Dihydronarciclasine,1

As an extension of structure-activity relationship studies of pancratistatin (1), various techniques were first evaluated for separating the mixtures of 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a) isolated from Hymenocallis littoralis. An efficient solution for that otherwise difficult separation then allowed the lactam carbonyl group of protected (4c and 5c) alcohols 2b and 3a to be reduced employing lithium aluminum hydride. Cleavage (TBAF followed by H2SO4) of the silyl ester/acetonide protected 6a gave amine 8. X-ray crystal structure determinations were employed to confirm the structures of 3,4-acetonide-5-aza-6-deoxynarciclasine (6b), 5-aza-6-deoxynarciclasine (8a), and 5-aza-6-deoxy-trans-dihydronarciclasine (9a, 9b). Against the murine P388 lymphocytic leukemia and a panel of human cancer cell lines, the parent natural products, 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a), were found to generally be more cancer cell growth inhibitory (GI50 0.1 to <0.01 microg/mL) than the compounds with structural modifications such as amine 8 by a factor of 10 or more. The trans ring juncture of isocarbostyril 3a proved to be an important modification of narciclasine (2a) for improving cancer cell growth inhibition in this series.

Synthesis of (+)-Allocyathin

(+)-Allocyathin is isolated from the fruit bodies of Cyathus earlei. It has antibacterial and antifungal properties. The challenge in the synthesis of Allocyathin is the construction of the characteristic angularly fused 5-6-7 tricyclic skeleton, containing a conjugated trienal motif and 1,4-anti stereocenters at each ring junction.

Enantioselective Synthesis of Furo[2,3-b]furans, a Spongiane Diterpenoid Substructure

[structure: see text] A short and enantioselective synthesis of cis-fused 5-oxofuro[2,3-b]furans, being found in many spongiane diterpenoid natural products, is reported starting from inexpensive methyl 2-furoate. Moreover, the acid-catalyzed rearrangement of the furo[2,3-b]furan framework A to B is observed for some derivatives, suggesting a simple connection between natural products differing in the absolute configuration of the 3a,6a ring junction.

Neridienone A, a pregnane from the roots ofNerium oleander

In the title compound, 12β-hydroxy­pregna-4,6,16-triene-3,20-dienone, C21H26O3, rings A and B are in almost half-chair conformations, ring C is in a chair conformation and ring D is in a 14α-envelope conformation. The A/B ring junction is quasi-trans, whereas the B/C and C/D ring junctions both approach trans character. The mol­ecule as a whole is slightly convex towards the β side. Intra- and inter­molecular hydrogen bonding, together with van der Waals inter­actions, plays a major role in the crystal structure.

Stability Relationships in Bicyclic Ketones

Calculated energy differences between cis- and trans- fused bicyclic ketones are provided for bicyclo(3.3.0)octanones, bi- cyclo(4.3.0)nonanones, bicyclo(5.3.0)decanones, bicyclo(6.3.0)un- decanones and the corresponding hydrocarbons with and without angular methyl groups. The calculations were performed for HF/6- 31G* and MP2/6-31G* optimized geometries. The latter were used for subsequent single-point energy MP2/6-311G* calculations. Whenever possible, the calculated energy differences were com- pared with experimental data and found to correspond well. The results of the calculations provide a complete picture of expected energetic differences in bicyclic ketone series and will be useful in both instruction and synthetic planning. Anyone who has ever taught a course on natural product synthesis has had a need to illustrate conformational equi- libria relationships and energy differences in cis- and trans-fused ring systems. The latter topic becomes very relevant in discussions of strategy and tactics of design in terpene total synthesis. Intuitively, most of us are aware that bicyclo(3.3.0)octanes prefer cis fusion by a sufficient energy margin to obviate any need for concern in synthet- ic sequences that are subject to thermodynamic control. With larger rings this situation becomes less clear and in the area of perhydroazulene terpenoid synthesis, for ex- ample, the energetic differences between cis- and trans- fused ketones are such that stereospecific construction of either diastereomer poses serious problems in situations where bridge enolization occurs. In the bicyclo(4.3.0)de- canes placement of a carbonyl next to the ring junction is almost always required for introduction of further substit- uents and is frequently introduced to such a position by ring expansion, ring contraction, or cycloaddition tactics. Mixtures of diastereomers result in thermodynamically controlled processes or through further manipulation of products and serious tactical obstacles must be overcome in maintaining stereocontrolled preparation of targets. The primary literature, as well as monographs that focus on stereochemistry, cover the energetics of ring fusion to some extent. However, the data is relatively diffused throughout the published work in physical organic chem- istry and, to our knowledge, no single publication offers a comparative view of the commonly encountered ring sys- tems. Some attempts at discussion of this topic have been made in Mundy's book 2 and in Eliel's stereochemistry text 3 but most available data is dispersed throughout the primary literature. The purpose of this manuscript is to provide calculated energy differences of bicyclo(m.3.0)alkanones as iso- meric pairs with respect to the ring fusion. Whenever available, the calculations are compared with experimen- tal data from the literature for either the ketone or the parent hydrocarbon or both. It is hoped that this compila- tion is of equal use to instructors as it is to practitioners of synthesis. The calculated energies and their differences are present- ed in Table 1, Table 2, Table 3, and Table 4. Table 1 Energy Differences between cis- and trans- Bicyclo(3.3.0)octanes, cis- and trans-Bicyclo(3.3.0)octan-1-ones, and their Angularly Methylated Derivatives 8

The Intramolecular Aromatic Electrophilic Substitution of Aminocyclopropanes Prepared by the Kulinkovich–de Meijere Reaction

AbstractThis article describes new examples of intramolecular Kulinkovich–de Meijere reactions applied to carboxylic amides bearing an olefin moiety and an aromatic ring at a suitable position. Upon heating, the aminocyclopropanes thus obtained undergo intramolecular aromatic electrophilic substitution to afford polycyclic systems. Among the various starting materials prepared, best results are obtained from indole and phenol derivatives. In each case, a benzylic quaternary centre is introduced at the newly‐formed ring junction. On one example, the efficiency of the cyclisation has been dramatically improved using a catalytic amount of para‐toluenesulfonic acid. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)

Cycloisomerization of Enynes Catalyzed by Iron(0)−Ate Complexes

The 18-electron half-sandwich iron(0) complex [CpFe(C2H4)2] [Li(tmeda)] (1a), which is readily available in multigram quantities from inexpensive starting materials (ferrocene, ethylene, Li sand), is shown to be an efficient catalyst for the Alder-ene reaction of various 1,6(7)-enynes. Thereby, the presence of the labile alkene ligands in the ferrate catalyst is essential since the analogous complex [CpFe(CO)2]Na is catalytically incompetent. The cycloisomerizations catalyzed by 1a are compatible with various functional groups and turned out to be highly diastereoselective with regard to the configuration of the newly formed alkenes as well as relative stereochemistry at the ring junction. The alkyne moiety in the substrates may be terminal, silylated, or substituted with various groups, including cyclopropane rings. Likewise, the alkene substructure can be varied to a large extent, with cycloalkenes of ring sizes >/=7 being particularly suitable.

Structural identification of ladderane and other membrane lipids of planctomycetes capable of anaerobic ammonium oxidation (anammox)

The membrane lipid composition of planctomycetes capable of the anaerobic oxidation of ammonium (anammox), i.e. Candidatus'Brocadia anammoxidans' and Candidatus'Kuenenia stuttgartiensis', was shown to be composed mainly of so-called ladderane lipids. These lipids are comprised of three to five linearly concatenated cyclobutane moieties with cis ring junctions, which occurred as fatty acids, fatty alcohols, alkyl glycerol monoethers, dialkyl glycerol diethers and mixed glycerol ether/esters. The highly strained ladderane moieties were thermally unstable, which resulted in breakdown during their analysis with GC. This was shown by isolation of a thermal product of these ladderanes and subsequent analysis with two-dimensional NMR techniques. Comprehensive MS and relative retention time data for all the encountered ladderane membrane lipids is reported, allowing the identification of ladderanes in other bacterial cultures and in the environment. The occurrence of ladderane lipids seems to be limited to the specific phylogenetic clade within the Planctomycetales able to perform anammox. This was consistent with their proposed biochemical function, namely as predominant membrane lipids of the so-called anammoxosome, the specific organelle where anammox catabolism takes place in the cell.

5,8′-Dimethoxy-3H-1-benzofuran-2-spiro-2′-chroman

The crystal structure of the title compound, C18H18O4, has been investigated to establish the relative stereochemistry at the spiro ring junction. Each of the O atoms adjacent to the junction is an axial substituent of the neighboring ring; the adoption of this conformation is likely to be due to anomeric effects.

On the structure and spectroscopic properties of two 13-hydroxylupanine epimers

The crystal structures of 13α- and 13β-hydroxylupanines present a rare case of unexpected configuration and conformation of bis-quinolizidine alkaloid free bases. The configuration of A/B and C/D ring junctions is trans– cis and quasi trans– cis in α and β epimers, respectively. Ring C adopts a distorted chair form in both of them which is unusual for lupin alkaloids free bases. Such a drastic rearrangement of electronic configuration at N16 is caused by intermolecular hydrogen bonds formation between the OH and C O groups. In spite of different orientations of the OH groups - an axial or an equatorial in α and β epimers, respectively, the hydrogen bond geometry is the same in both crystal structures. This causes different distortions in all four rings of bis-quinolizidine skeletons. The Duax-Norton approach has been used to analyze them. In solution, both epimers occur in conformational equilibrium with considerable domination of the C-boat conformer (85–90%). This conformation is stabilized by the other type of intermolecular hydrogen bonds in comparison with that operating in the solid. Intermolecular deuterium bonds between 13α- and/or 13β-hydroxylupanine molecules and the solvent CDCl 3 molecules as well as the N16⋯H–O association have been found to play a crucial role.