Unusual Ring Research Articles

Model studies for the stereoselective construction of the BC-ring of armatol F based on Ireland-Claisen rearrangement and relay ring-closing olefin metathesis

Armatol F, isolated from the red alga Chondria armata as a polyether triterpene, has a fused tricyclic ether moiety (BCD-ring) with an unusual cis ring junction at C18–C19 between the C- and D-rings. En route to the total synthesis of armatol F, the stereoselective construction of the C18 and C19 stereocenters by Ireland-Claisen rearrangement and the formation of the C-ring by relay ring-closing olefin metathesis were established through the synthesis of monocyclic (C-ring) and bicyclic (BC-ring) model compounds.

ChemInform Abstract: Unusual Ring Contraction by Substitution of 4-O-Activated-pentono-1,5-lactams with Cyanide. Stereospecific Synthesis of 6-Amino-1,4,5,6- tetradeoxy-1,4-imino-hexitols.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: An Unusual Samarium Diiodide Mediated Reductive Ring Contraction of a Tricyclic Oxazine to a Highly Functionalized Cyclopentane and Cyclobutane.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Three New Triterpenoids Containing Four-Membered Ring from the Fruiting Body of Ganoderma sinense

Methyl ganosinensate A (1), ganosinensic acid A (1a), and ganosinensic acid B (2), three new triterpenoids with an unusual four-membered ring skeleton produced by a bond across C-1 to C-11, were isolated from the fruiting body of Ganoderma sinense . Their structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and methyl ganosinensate A was confirmed by X-ray crystallographic analysis.

Unusual vascular ring anomaly associated with a persistent right aortic arch and an aberrant left subclavian artery in German pinschers

The objective of this study was to describe a specific form of persistent right aortic arch (PRAA) in three German pinscher dogs and to analyse the mode of inheritance in the breed. This type of PRAA is characterised by a left retro-oesophageal subclavian artery in combination with a ligamentum arteriosum originating at the aberrant left subclavian artery (PRAA-SA-LA). This rare combination of anomalies has only been reported in two isolated cases in other dog breeds and the occurrence of any form of PRAA was not previously known to occur in the German pinscher. In the present study, 18 cases of this congenital anomaly were ascertained and their high degree of relatedness and inbreeding could be shown through pedigree analysis. Three of the affected dogs underwent further clinical investigations, and post-mortem examination (two cases) and findings at surgery (one case) verified the diagnosis of PRAA-SA-LA. A monogenic autosomal recessive mode of inheritance was not likely.

Unusual electron density topology and intramolecular steric π–π interaction in 1,3,5,7-cyclooctatetraene

We explain the presence of the Cage Critical Point within the individual cyclooctatetraene ring as a result of the overlapping of p-type orbitals belonging to oppositely placed formally double CC bonds. This unusual ring topology is enabled by spatial arrangement of the double CC bonds in rigid skeleton of the COT ring in its natural tub-shaped conformation. Since the overlapping of the p-type orbitals may suggest some additional ‘ through the space’ π-electron delocalization, this interaction is investigated in detail. Our results show that this interaction should be considered as a steric one and no extra stabilization from ‘ through the space’ delocalization can be considered.

Expeditious synthesis of helianane and C-10 halogenated heliananes employing ring-closing metathesis

An expeditious synthesis of the marine sesquiterpene helianane enclosing an unusual benzoxocane ring system is described employing ring-closing metathesis as the key step. Helianane has been further converted to the naturally occurring C-10 bromo and chloro derivatives.

An unusual ring—A opening and other reactions in steroid transformation by the thermophilic fungus Myceliophthora thermophila

A series of steroids (progesterone, testosterone acetate, 17β-acetoxy-5α-androstan-3-one, testosterone and androst-4-en-3,17-dione) have been incubated with the thermophilic ascomycete Myceliophthora thermophila CBS 117.65. A wide range of biocatalytic activity was observed with modification at all four rings of the steroid nucleus and the C-17β side-chain. This is the first thermophilic fungus to demonstrate the side-chain cleavage of progesterone. A unique fungal transformation was observed following incubation of the saturated steroid 17β-acetoxy-5α-androstan-3-one resulting in 4-hydroxy-3,4-seco-pregn-20-one-3-oic acid which was the product generated following the opening of an A-homo steroid, presumably by lactonohydrolase activity. Hydroxylation predominated at axial protons of the steroids containing 3-one-4-ene ring-functionality. This organism also demonstrated reversible acetylation and oxidation of the 17β-alcohol of testosterone. All steroidal metabolites were isolated by column chromatography and were identified by 1H, 13C NMR, DEPT analysis and other spectroscopic data. The range of steroidal modification achieved with this fungus indicates that these organisms may be a rich source of novel steroid biocatalysis which deserve greater investigation in the future.

Formation and Reactivity of [(tacn)-N-CO-ReIIIBr(CO)2]+in Water: a Theoretical and Experimental Study

The chemistry of [(tacn)-N-CO-Re(III)(CO)(2)Br]X (X = Cl or Br), obtained in good yield from the reaction of fac-[(tacn)Re(I)(CO)(3)]Br (1, tacn = 1,4,7-triazacyclononane) with X(2) in water, is described. The [(tacn)-N-CO-Re(III)(CO)(2)Br]X complex (2 with X = Br(-); 2a with X = BrCl(2)(-)), which we have previously communicated, is characterized by an unusual three-membered ring acyl amide bond. Complex 2 is stable as a solid but is reactive in aqueous solution. Under basic conditions (1 M NaOH), reductive decarbonylation was observed, and the bis-carbonyl complex [(tacn)Re(I)(CO)(2)Br] (3) was obtained in quantitative yield. The Br(-) ligand in 3 could be replaced by CN(-), giving the neutral complex [(tacn)Re(I)(CO)(2)(CN)] (4). In acidic media (1 M HBr), complex 2 partially converted to the monocarbonyl mu-oxo bridged dinuclear complex {[(tacn)Re(III)(CO)Br](2)O}(2+) (5 as [PF(6)](-) salt). Under mild oxidative conditions the trioxo [(tacn)Re(VII)O(3)](ReO(4)(-)) (6) was formed almost quantitatively, and small amounts of the uncommon Re(VI) complex [(tacn)Re(VI)O(2)Br](ReO(4)(-)) (7) were identified. Mechanistic investigations at the density functional level of theory (DFT) showed that the elementary steps in the formation of 2 from 1 and 3 from 2 involved reactions of the complexes with hydroxide. The calculated pathway is strongly exothermic (ca. -137 kcal/mol), confirming the energetically and kinetically highly favored formation of 3. The X-ray structures of 2a and 3-5 are reported and discussed.

The origin of an unusual tuff ring of perlitic rhyolite pyroclasts: The last explosive phase of the Ramadas Volcanic Centre, Andean Puna, Salta, NW Argentina

A thick sequence of bedded pyroclastic deposits, comprised largely of crystal poor, partially flow-banded perlite fragments defines the remains of a tuff ring around the eastern margin of the Miocene Ramadas Volcanic Centre (RVC), Central Andes, NW Argentina. In numerous quarry exposures, planar bed-forms dominate, but low-angle cross-stratification, lensoidal truncations and lateral pinching and swelling of cm–dm scale bed-forms occur, consistent with pyroclastic surge as the dominant transport and depositional mechanism. Intercalated are mantling, very fine grained, well-sorted, mm–cm scale planar ash layers that represent deposition from pyroclastic fall out and are most likely the products of co-surge ash clouds. Also observed are thick m-scale, laterally continuous, poorly-sorted horizons that are interpreted as pyroclastic flow deposits. Grainsize variations within the > 70 m thick succession range from fine ash to coarse lapilli, with occasional large blocks reaching 20 cm. Clast vesicularities are typically very low. The sequence constitutes a rhyolitic tuff ring around the proximal margins of the RVC. Stratigraphic relationships indicate that the tuff ring was developed following cessation of the major plinian eruption phase of the RVC. A series of pyroclastic density currents and associated ash clouds is inferred to have resulted in the construction of the rhyolitic tuff ring, with deposition focussed on the eastern and southern margins of the central vent. The fine-grained nature of the deposits and low clast vesicularity are consistent with some degree of magma:water interaction during fragmentation. Pervasive perlitic fracturing of clasts found within the tuff deposits also indicates hydration and an extended, post-depositional hydration of the pyroclastic sequence, due to the influence of meteoric water, is likely to have occurred, with deposit permeability, clast specific surface and climate influential in facilitating additional textural modification of pyroclasts.

A New Lycopodium Alkaloid, Lycoposerramine‐R, with a Novel Skeleton and Three New Fawcettimine‐Related Alkaloids from Lycopodium serratum

Abstractmagnified imageA new Lycopodium alkaloid, lycoposerramine‐R, possessing an unusual tetracyclic ring system, was isolated from Lycopodium serratum. Its structure as well as those of three new co‐existing fawcettimine‐related alkaloids were elucidated by means of extensive spectroscopic analysis.

Spectroscopic analyses and chemical transformation for structure elucidation of two novel indole alkaloids from Gelsemium elegans

Two new monoterpenoid oxindole alkaloids, gelsevanillidine ( 1) having an additional vanillin residue on gelsenicine-type alkaloid and gelseoxazolidinine ( 2) possessing an unusual oxazolidine ring, were isolated from Gelsemium elegans. To confirm their structures, the chemical transformation of a humantenine-type alkaloid into gelsevanillidine ( 1) and the deacetoxy derivative of gelseoxazolidinine was performed.

Quinoprotein ethanol dehydrogenase from Pseudomonas aeruginosa: the unusual disulfide ring formed by adjacent cysteine residues is essential for efficient electron transfer to cytochrome c 550

All pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenases contain an unusual disulfide ring formed between adjacent cysteine residues. A mutant enzyme that is lacking this structure was generated by replacing Cys105 and Cys106 with Ala in quinoprotein ethanol dehydrogenase (QEDH) from Pseudomonas aeruginosa ATCC17933. Heterologously expressed quinoprotein ethanol dehydrogenase in which Cys-105 and Cys-106 have been replaced by Ala (Cys105Ala/Cys106Ala apo-QEDH) was successfully converted to enzymatic active holo-enzyme by incorporation of its cofactor PQQ in the presence of Ca(2+). The enzymatic activity of the mutant enzyme in the artificial dye test with N-methylphenazonium methyl sulfate (PMS) and 2,6-dichlorophenol indophenol (DCPIP) at pH 9 did not depend on an activating amine which is essential for wild type activity under these conditions. The mutant enzyme showed increased Michaelis constants for primary alcohols, while the affinity for the secondary alcohol 2-propanol was unaltered. Surprisingly, for all substrates tested the specific activity of the mutant enzyme in the artificial dye test was higher than that found for wild type QEDH. On the contrary, in the ferricyanide test with the natural electron acceptor cytochrome c(550) the activity of mutant Cys105Ala/Cys106Ala was 15-fold lower than that of wild type QEDH. We demonstrate for the first time unambiguously that the unusual disulfide ring is essential for efficient electron transfer at pH 7 from QEDH to its natural electron acceptor cytochrome c(550).

5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[2-(2-chloroethoxy)ethoxy]-2,8,14,20-tetrasulfonylcalix[4]arene

Mol­ecules of the title compound, C56H76Cl4O16S4, have crystallographic C 2 symmetry and adopt a 1,3-alternate conformation where the four –OCH2CH2OCH2CH2Cl groups are located alternately above and below the virtual plane (R) defined by the four bridging S atoms. The dihedral angles between the plane (R) and the phenolic rings are 72.85 (7) and 74.57 (7)°. An unusual 24-membered macrocyclic ring is formed in the crystal structure with an array of eight intra­molecular C—H⋯O hydrogen bonds between the ether arm H atoms and the sulfonyl O atoms. In the supra­molecular structure, the mol­ecular components are linked into infinite zigzag one-dimensional chains by a combination of four inter­molecular C—H⋯O hydrogen bonds, forming R 2 2(13), R 2 2(16), R 2 2(21) and R 2 2(26) ring motifs. These chains are augmented into a wave-like two-dimensional network by weak C⋯O inter­actions. One tert-butyl group shows rotational disorder, and one CH2CH2Cl group is disordered over two orientations; the site-occupation factors are 0.756 (6) and 0.244 (6) for the two tert-butyl groups, and 0.808 (3) and 0.192 (3) for the two CH2CH2Cl units.

Unusual chalcogen-boron ring compounds: the gas-phase structures of 1,4-B4S2(NMe2)4 and related molecules

The structure of 1,4-B4S2(NMe2)4 has been determined by gas-phase electron diffraction and quantum chemical calculations and is compared with the known solid-state structure. While these structures are similar, with a twisted ring geometry [the dihedral angle S-B-B-S from electron diffraction is 75.4(16) degrees], they are strikingly different to the solid-state structure of 1,4-B4O2(OH)4, which is planar. Using quantum chemical calculations, the combinations of O or S in the ring and OH or NMe2 as the substituent have been studied and it has been shown that there are two separate causes of the twisted ring. Since the calculated (and observed) structure of 1,4-B4O2(OH)4 is planar but that of 1,4-B4S2(OH)4 is twisted, it is concluded that the inclusion of sulfur in the ring twists the structure by approximately 40 degrees. By comparing the structures of 1,4-B4S2(OH)4 and 1,4-B4S2(NMe2)4 it has been determined that the twist caused by the NMe2 groups is around 30 degrees.

Supramolecular association of 1,2,5-chalcogenadiazoles: an unexpected self-assembled dissymetric [Se⋯N]2 four-membered ring

The structure of a self-assembled system containing benzoselenadiazole with the corresponding cationic N-methyl salt was determined by X-ray diffraction analysis. The assembly has a distinct tendency to establish intermolecular links in the solid state through secondary intermolecular bonding Se⋯N interactions. In such supramolecular association, the observation of an unusual asymmetric four-member ring [Se⋯N]2 with a short contact of 2.573 A and a long contact of 2.966 A was observed.

Unusual ring annulation during condensation of acetylacetone with pyrrole

During the attempted synthesis of bisdipyrromethane from acid-catalyzed condensation of acetylacetone with pyrrole, an unexpected ring annulation led to the formation of 2,3-dihydro-1 H-pyrrolizine-bridged bipyrrole.

Biosynthetic Origins of the Ionophore Antibiotic Indanomycin

The pyrroloketoindane antibiotic indanomycin is produced by Streptomyces antibioticus NRRL 8167. These hybrid nonribosomal peptide-polyketide ionophore antibiotics are characterized by the presence of an unusual indane ring system, and there is interest in identifying the biochemical mechanisms guiding its biosynthesis. Following incorporation of [1-(13)C]-labeled precursors, the primary metabolic origins of indanomycin were determined to be one unit of L-proline, six units of malonyl-CoA and two units each of methylmalonyl-CoA and ethylmalonyl-CoA.

Analogues of Marine Pyrroloiminoquinone Alkaloids: Synthesis and Antitumor Properties

Marine organisms provide a valuable source for natural products. In recent years, iminoquinone alkaloids including makaluvamines, isobatzellines, tsitsikammamines and wakayin, have emerged as an essential class of marine metabolites due to their prominent biological activities and unusual ring structures. This review focuses on synthesis and antitumor evaluation of analogues of these products.

Strategies for the Total Synthesis of C2−C11 Cyclized Cembranoids

The C2-C11 cyclized cembranoids, which include the eunicellins (also known as the cladiellins), briarellins, asbestinins, and sarcodictyins, are secondary metabolites isolated from gorgonian octocorals and soft corals. An unusual oxatricyclic ring system containing a hydroisobenzofuran and an oxonene unit with stereogenic centers residing at C1-3, 9, 10, and 14 is common to the eunicellins, briarellins, and asbestinins. However, the location of the cyclohexyl methyl groups (C11 versus C12) and the oxidation level of the sixand nine-membered rings differ among the three classes. Faulkner has proposed that the cyclization of the cembranoid diterpene skeleton initiates a biosynthetic pathway that leads to all four subclasses of these unusual molecules (Figure 1). Beginning with the cembrane skeleton, C2-C11 cyclization provides the cladiellin framework. An intramolecular etherification of the cladiellin tricycle affords the tetracyclic framework of the briarellin subclass, and a subsequent 1,2-suprafacial methyl shift of the briarellin structure is postulated to deliver the asbestinins as the class that is furthest evolved from the cembrane skeleton. The presence of multiple structural types in a common organism provides circumstantial evidence for Faulkner’s proposed biosynthetic pathway. The isolation of a cembrane metabolite with cladiellin metabolites in Alcyonium molle and with asbestinin metabolites in Briareum steckii are specific examples. The sarcodictyins are also proposed to arise from a C2-C11 cyclization of the cembrane skeleton; however, in these systems, the cyclization results in a fused cyclohexane and oxonane in place of the hydroisobenzofuran of the cladiellins, briarellins, and asbestinins. As a result of this significant structural variation of the sarcodictyins, the synthetic approaches to these molecules are quite different than those for the other three related subclasses. This review will cover efforts toward the eunicellins, briarellins, and asbestinins but will not cover efforts toward the total synthesis of the sarcodictyins. Eunicellin was the first reported member of the C2-C11 cyclized cembranoid natural products, isolated in 1968 by Djerassi and co-workers from the soft coral Eunicella stricta found off the coast of Banyuls-sur-Mer in France. Since this discovery, over 100 unique secondary metabolites of gorgonian octocorals have been characterized, including the first asbestinin in 1980 and the first briarellin in 1995. A wide range of structural diversity is displayed by this group of marine natural products. The natural role of these cembranoids is proposed, based upon mollusk and fish lethality assays, to involve predation deterrence. Upon further investigation, several of the members of these subclasses have demonstrated significant pharmacological potential. Particularly, these diterpenes have been shown to exhibit in vitro cytotoxicity against various cancer cell lines, anti-inflammatory properties, antimicrobial activities, and histamine and acetylcholine antagonism. The fascinating molecular architecture of these cembranoids, as well as their potential as therapeutic agents, has sparked much interest in the synthetic community over the past decade. A variety of approaches toward these challenging structural motifs have been investigated and several total syntheses have been accomplished. Efforts toward the total synthesis of the cladiellins, briarellins, and asbestinins are the subject of this review.