Dioxolane Ring Research Articles

(Z)-4-[(S)-2,2-Dimethyl-1,3-dioxolan-4-ylmethylidene]-2-phenyl-1,3-oxazol-5(4H)-one

In the title compound, C15H15NO4, the whole molecule, except for the dioxolane ring, adopts a nearly planar conformation. The dioxolane ring, which has an envelope conformation, is mainly situated on the si,si diastereotopic face of the olefinic bond. In the crystals of the title compound, rows of mol­ecules are held together along the x direction by C⋯O intermolecular hydrogen bonds.

Investigation of polymerizability of ο-alkenyldioxolanes with α-olefins and alkyl vinyl ethers by modified Ziegler-Natta catalysts

Results are presented of an investigation on the polymerizability of functional olefins, such as allylisopropylidene glycerol (AIPG) and undecenylisopropylidene glycerol (UIPG), in the presence of conventional and modified Ziegler-Natta catalysts based on TiCl 4 or MgCl 2 -supported titanium and triisobutylaluminum, hexaisobutyltetraalumoxane, or bisdiethylaluminum sulfate. Homopolymerization experiments were performed on AIGP at temperatures of -78, 25, and 50°C ; only those at 50°C provided appreciable amounts of polymeric materials insoluble in methanol, whose structures comprise monomeric units derived from opening both dioxolane rings and vinyl double bonds. In spite of all attempts and precautions, polymerization experiments carried out on mixtures of the functional olefins AIPG and UIPG with either 4-methyl-1-pentene or isopropyl vinyl ether gave rise to the homopolymers of the nonfunctional α-olefin and of the vinyl ether, without any appreciable amount of either copolymers or homopolymers of the dioxolane containing monomers.

2,3,10,11-Tetraphenyl-1,4,9,12-tetraoxadispiro[4.2.4.2]tetradeca-6,13-diene

The crystal structure of the title compound, C34H28O4, consists of discrete molecules held together by normal van der Waals interactions. The molecule possesses a crystallographic twofold axis passing through the midpoints of the two double bonds of the cyclohexadiene ring. The asymmetric C atoms in the dioxolane rings have an S,S configuration.

(22S)-21-Acetoxy-11β-hydroxy-16α,17α-methylorthoacetoxypregna-1,4-diene-3,20-dione

In the title compound, methyl (22S)-11β-hydroxy-16α,17α-[(methoxy)(methyl)methylenedioxy]pregna-1,4 -diene-3,20-dione-21-acetate, C 26 H 34 O 8 , part of the orthoacetate group forms the dioxolane ring (E) fused with the steroid skeleton at the C16 and C17 atoms. Ring A is planar, rings B and C adopt chair conformations, while rings D and E have conformations midway between half-chair and envelope. Intermolecular O11-H...O3 hydrogen bonds are formed. The new chiral center at atom C22 of the dioxolane ring has an S configuration and the conformation of the ring, closed at C22, is comparable with the conformations found for the (22R) diastereoisomers of similar compounds.

Synthesis and Characterization of Photolabile Choline Precursors as Reversible Inhibitors of Cholinesterases: Release of Choline in the Microsecond Time Range

Three o-nitrobenzyl ether derivatives of choline (compounds A−C) were synthesized as photolabile cholinesterase inhibitors in order to study the mechanism of choline release from the enzyme active site. The key step of the synthesis was a simple and efficient Lewis acid-catalyzed opening of dioxolane rings derived from o-nitrobenzaldehyde and o-nitroacetophenone. Laser flash photolyses of compounds A−C were analyzed by UV spectroscopy, HPLC, and an enzymatic assay for choline. The quantum yields of photoconversion were determined, and the kinetics of choline release were analyzed by studying the decay of the transient aci-nitro intermediate at 405 nm. The observed rates varied considerably in function of both pH and the substituent at the α-benzylic position. Furthermore, we demonstrated that all three compounds possessed reversible inhibitory properties on both purified Torpedo acetylcholinesterase and purified human plasma butyrylcholinesterase. Compound A, O-[1-(2-nitrophenyl)ethyl]choline iodide, which displayed the highest quantum yield (0.27) and the most rapid photolysis rate (6.8 × 104 s-1 at pH 6.5), represents therefore an interesting tool for the study of the fast process of choline release from cholinesterases by time-resolved Laue crystallography.

Biosynthetic capacities of actinomycetes. 5. Dioxolides, novel secondary metabolites from Streptomyces tendae.

Dioxolides, a novel class of secondary metabolites were detected by a HPLC-diode array screening technique in the culture filtrate of Streptomyces tendae Tu 4042. The compounds show no biological activity against Gram-positive and Gram-negative bacteria, yeasts and fungi. Besides dioxolides, which consist of an unusual substituted dioxolane ring, anhydroshikimate and para-hydrobenzamide were detected by this technique. Both compounds were not yet described as natural products.

Muscarinic Antagonist: 8,8-Dimethyl-3',3'-diphenylspiro(8-azoniabicyclo[3.2.1]octane-3,2'-1',3'-dioxolane)-4'-one Iodide

The molecular structure of the title compound, C 23 H 26 NO 3 + .I - , BVT44Me, has been compared to that of the related compound 8,8-dimethyl-3,3-diphenyl-1,4-dioxa-8-azoniaspiro[4.5]decan-2-one iodide, spiro-DAMP [Sabatino, Recanatini, Tumiatti & Melchiorre (1994), Acta Cryst. C50, 640-645]. The dioxalane ring adopts an envelope conformation in spiro-DAMP (the ether O atom being out of the plane of the ring) and a twist conformation in BVT44Me (the ether O and the C atom at the spiro position being out of the plane of the ring). This makes the spatial orientations of the substituents of the dioxolane ring slightly different. The crystal packing in BVT44Me is stabilized by electrostatic interactions and van der Waals contacts. Charge-charge interactions place the I - ion close to the quaternary ammonium group. These interactions may be classified as hydrogen bonds (CH...I).

Synthesis and conformational analysis of the Amadori compound N-(2,3:4,5-di- O-isopropylidene-1-deoxy- β- d-fructopyranos-1-yl)- l-tyrosine benzyl ester

The title compound, a precursor in the synthesis of other analogues of Amadori type, was prepared and characterized by X-ray structure analysis and NMR spectroscopy. The molecule crystallized in the orthorhombic space group P2 12 12 1 with a = 10.441(2), b = 10.894(2), c = 24.686(4) A ̊ , Z = 4 . The molecule is flexible even in solid state; at 100 K two orientations of the benzyloxy group are present in the unit cell. Therefore, molecular mechanics and molecular dynamics simulations were used to study its conformational changes. The results obtained were compared with experimental observations. The comparative analysis revealed that the two conformers detected in the crystal are different from the energetically favourable conformations in Me 2SO solutions. Rotations about both C-N bonds affect the global molecular conformation. The β-d-fructopyranose moiety blocked with two dioxolane rings is the less flexible part of the molecule; in the solid state and in Me 2SO- d 6 it is in the skew conformation.

Four Isomeric Dioxolane Derivatives of D-Camphorquinone

The bicyclo[2.2.1]heptane unit is essentially invariant in all four structures, reflecting its rigid nature. The four isomers (1S,2S,4R,4'S)-, (1S,2S,4R,4'R)-, (1S,2R,4R,4'R)- and (1S,2R,4R,4'R)-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one-2-spiro-2'-(4'-chloromethyl-1',3'-dioxolane), C 13 H 19 ClO 3 , have different positions of substitution by the CH 2 Cl group in the ethylene segment of the dioxolane ring. In each case, this ring has an envelope conformation but the identity of the flap atom varies. All four molecules have a similar overall shape and hence give similar packing patterns, resulting in close correspondence or simple relationships for the four sets of unit-cell parameters and the space groups of the structures.

Pesticides labelled with 14C. II. Synthesis of propiconazole labelled in three different positions

AbstractPropiconazole was labelled with 14C in three different positions: in the benzene ring, in the position 5 of the dioxolane ring, and in the triazole ring. The synthesis of three new key intermediates [(m‐dichloro[U‐14C]benzene], 1,2,4‐[U‐14C]triazole, [1‐14C]‐pentane‐1,2‐diol) were also elaborated.

The X-ray Crystal and Molecular Structure of 5-Amino-1-(2,3:5,6-Di-O-isopropylidene-α-D-mannofuranosyl) Imidazole-4-carboxamide

Abstract 5-Amino-1-(2,3:5,6-di-O-isopropylidene-α-D-mannofuranosyl) imidazole-4-carboxamide (ADIMIC) crystallizes with six molecules in a hexagonal unit cell of space group P63.. The imidazole ring is closely planar, the furanose ring pucker is O1′ endo-C4′ exo, and the dioxolane rings are puckered C6′ endo-O6′ exo and C7′ endo-O3′ exo. In addition to an intramolecular hydrogen bond from the 5-amino hydrogen to the 4-carboxamide oxygen, a circuit of intermolecular hydrogen bonds links nearly coplanar imidazole rings.

Conformational effects on retinoid receptor selectivity. 2. Effects of retinoid bridging group on retinoid X receptor activity and selectivity.

The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three RAR subtypes or RXR alpha. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and 9E-double bond of 9-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXR alpha activity and selectivity. In addition, the beta-geranylidene and 20-methyl-(11E,13E)-dienoic acid groups of 9-cis-retinoic acid are replaced by a 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXR alpha selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5-thienyl group or the 9-cis-retinoic acid methylpentadienoic acid terminus.

Biodegradation of different carboxylate types of cleavable surfactants bearing a 1,3‐dioxolane ring

AbstractThe biodegradability of new carboxylate types of “acid‐sensitive” cleavable surfactants bearing a 1,3‐dioxolane ring was measured by the biochemical oxygen demand (BOD) method in the presence of activated sludge. The result for sodium dodecanoate, measured under the same conditions, was used as a standard for evaluating the biodegradability of these cleavable surfactants. For cleavable surfactants derived from epoxides and oxocarboxylates, the biodegradation was considerably influenced by the length of the lipophilic alkyl chain, the presence of the oxymethyl moiety in the lipophilic group, and the number of methylene units between the dioxolane ring and the carboxylate group. For another type of cleavable surfactant, 2‐(long‐chain alkyl)‐1,3‐dioxolane‐4,5‐dicarboxylate, the biodegradation rate for the compound, bearing a proton at position 2 in the dioxolane ring, is faster than that for the corresponding compound bearing a methyl group at position 2.

Conformational and configurational study of 1,3‐dioxolanes by proton and carbon NMR spectroscopy

AbstractThe configurational and conformational properties of six 4‐trimethylammoniummethyl 2,2‐disubstituted 1,3‐dioxolanes were studied using NOE experiments and vicinal coupling constants. Selective 1D NOE experiments proved to be effective tools in the configurational assignment of C‐2 relative to C‐4. The preferred conformation of the dioxolane ring and the exocyclic group at C‐4 was obtained by employing vicinal coupling constants and NOE results. The 1H and 13C NMR chemical shifts show stereochemically dependent trends. Quantitative analysis of conformer populations was performed using Haasnoot et al's equation. The N+(CH3)3 group was found to be synclinal with respect to the heterocyclic O‐3 atom and points outside the ring. When a phenyl group is present at C‐2, the 4‐CH2N+— group in a trans relationship to the 2‐phenyl ring was found to occur prevalently in a pseudo‐axial orientation, whereas it was established to be prevalently pseudo‐equatorial when cis with respect to the phenyl ring.

The Oxygenation of Vinylcyclopropanes as an Entry into Stereoselective 1,3-Diol Synthesis

Chalcogen radical catalyzed addition of molecular oxygen (3O2) across the carbon-carbon bond of suitably activated vinylcyclopropanes affords 1,2-dioxolane products in moderate to excellent yield. Stereoselective preparation of either the syn or the anti dioxolane ring can be achieved by carefully balancing the steric and electronic characteristics of the vinylcyclopropane substituents. A mechanistic rationale for this complex multi-step transformation, including a discussion of the structural basis for product diastereoselectivity, is offered. Reductive cleavage of the 1,2-dioxolane ring’s oxygen-oxygen bond provides the target syn or anti 1,3-diols in good yield.

Fluorine-18-labeled progestin 16 alpha, 17 alpha-dioxolanes: development of high-affinity ligands for the progesterone receptor with high in vivo target site selectivity.

We describe the synthesis and tissue biodistribution of two 21-[fluoro-18F]progestin 16 alpha, 17 alpha-furanyl ketals, potential agents for imaging progesterone receptor (PR)-positive breast tumors in humans, using positron emission tomography. 21-Fluro-16 alpha, 17 alpha-[(R)-(1'-alpha-furylmethylidene)dioxy]-19- norpregn-4-ene-3,20-dione (endo-10a) and 21-fluoro-16 alpha, 17 alpha-[(R)-(1'-alpha-furylethylidene)dioxy]-19- norpregn-4-ene-3,20-dione (endo-10b) were chosen for radiochemical synthesis from a series of seven novel progestin 16 alpha, 17 alpha-(furanyldioxolanes) on the basis of their high relative binding affinity to PR (190% and 173%, respectively, relative to R5020 = 100%), their low nonspecific binding (NSB) (log P o/w = 3.87 and 4.13, respectively), and their resulting high binding selectivity indices (BSI; i.e., the ratio of their PR binding affinity to nonspecific binding). Radiochemical synthesis of these two species in high radiochemical purity and at high effective specific activity was accomplished by treatment of the corresponding diastereomerically pure 21-trifluoromethanesulfonates with fluorine-18 anion. In tissue biodistribution studies in estrogen-primed immature female Sprague-Dawley rats, both [18F]-endo-10a and [18F]endo-10b demonstrated high PR-selective uptake in the principal target tissues, the uterus and the ovaries, and relatively low uptake in fat and bone. The metabolism at the 21-position in these progestins (as monitored by in vivo defluorination) appears to be less than that in other 21-fluoroprogestins; this may reflect steric inhibition of metabolism at this site due to the bulk of the furan-substituted dioxolane ring at the 16 alpha, 17 alpha-position. Comparison with other fluorine-18-labeled progestins shows that the PR-specific uptake in uterine tissue correlates with the BSI of the ligand and that the fat uptake correlates with the NSB of the ligand at high levels of statistical significance. These two dioxolanes may prove to be useful as breast tumor-imaging agents in humans.

Dioxolane nucleosides and their phosphonate derivatives: synthesis and hydrolytic stability

Several new nucleoside (12–15) and nucleoside phosphonate (27–30) analogues derived from (±)-cis- and -trans-2-hydroxyrnethyl-4-methyl-1,3-dioxolane have been prepared and their configurations assigned by 1H NMR spectroscopy. First-order rate constants for the acid-catalysed hydrolysis of the dioxolane ring have been determined at different hydronium ion concentrations. The phosphonate group accelerates the hydrolysis at pH > 2 by 2 orders of magnitude, while at pH < 1 the hydrolytic stabilities of the nucleoside analogues and their phosphonate derivatives are comparable. The possible reasons for this rate-enhancement are discussed on the basis of the reaction mechanism.

β‐ラクタム環構築における異なる金属種を用いる立体化学のスイッチング

The importance of the stereodivergent synthesis of both enantiomers of β-lactams is ever increasing in connection with the structure-activity relationship study and the development of new derivatives in the β-lactam antibiotics. In this account stereocontrol at the C-3 and C-4 carbons of β-lactams using metal ester enolate-imine condensation reactions is discussed. The addition of an achiral ester enolate with a chiral imine possessing a dioxolane ring derived from (2S, 3S)-1, 4-dimethoxy-2, 3-butanediol as a chiral auxiliary is presented, in which 4-monosubstituted, 3, 4-disubstituted, and 3, 3, 4-trisubstituted β-lactams are prepared in a highly stereodivergent manner simply by switching metal ester enolate species. The application to the stereoselective synthesis of 1β-methylcarbapenem from 4-monosubstituted β-lactam is conducted by the use of selective hydrogenation reaction as a crucial step. The addition of an achiral ester enolate with a chiral imine having an auxiliary derived from phenylglycine at the nitrogen and the reaction of a chiral ester possessing arylsulfinyl group as an auxiliary at the α-position to the carbonyl with an achiral imine are also described for the stereodivergent synthesis of each of β-lactams from a single chiral source.

Preparation and Structural Analysis of Several New α,α,α′,α′‐Tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols (TADDOL's) and TADDOL analogs, their evaluation as titanium ligands in the enantioselective addition of methyltitanium and diethylzinc reagents to benzaldehyde, and refinement of the mechanistic hypothesis

AbstractPreparation and screening of twenty new ligands, all analogs of α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL), for the Ti‐catalyzed asymmetric addition of methyltri(isopropoxy)titanium and diethylzinc to benzaldehyde are described. These ligands have the dioxolane ring of the TADDOL's replaced by cyclobutane, cyclopentane, cyclohexene, cyclohexane, bicyclo[2.2.1]heptene and ‐heptane and bicyclo[2.2.2]octene and ‐octane moieties; several have H‐atoms or alkyl groups in place of the aryl groups, and nine of them have C2 symmetry. X‐Ray crystallography and molecular mechanics are used to analyze the structure of the ligands, and two structural features appear to correlate with selectivity: (i) the torsion angle for the chelating O‐atom and the ortho‐C‐atom of the axial Ph group (a small, ca. 19°, angle is optimum, Fig.8) and (ii) the “degree of perpendicularity” of the axial Ph group (Fig. 9). Competition experiments indicate that TADDOL 1a catalyzes both the methyltitanium and diethylzinc additions ≥ 50 times faster than the related dioxolane analogs 12a, 12c, and 12e (Scheme 7), indicating that both axial and equatorial aryl groups (see Footnote 6) are necessary for ligand‐accelerated catalysis of these reactions. A refined mechanistic hypothesis is presented (Fig. 10) to explain the selectivities observed for these new ligands. Our analysis suggests that a combination of structural features appear necessary for good catalytic efficiency and high selectivity. These features, especially the rather subtle conformational effects, appear to be optimized (among the ligands tested) in the TADDOL's.

Molecular structure of N-(2-phenylethyl)amide of α-(1,1-ethylenedioxy)-ethyl γ-hydroxybutyric acid (I) and1H NMR spectra of (I) and N-(p-methoxybenzyl)derivative (III)

The spectroscopic and X-ray investigation of the N-(2-phenylethyl) amide of α-(1,1-ethylenedioxy)-ethyl-γ-hydroxybutyric acid are reported. The1H NMR spectra for the title structure and for the N-(p-methoxybenzyl) amide of α-(1,1-ethylenedioxy)-ethyl-γ-hydroxybutyric acid are given. The N-(2-phenylethyl)amide of α-(1,1-ethylenedioxy)-ethyl-γ-hydroxybutyric acid, C16H23O4N, crustallizes in the monoclinic space groupP21/c witha=21.547(5),b=6.333(2),c=11.822(3) A and β=101.01(2)°. The dioxolane ring has a half-chair conformation with ΔC2(O3)=2.4° and |φ|av=18.2°. The inconsiderable deviations from planarity of the six atoms of the amide group are caused mainly by twist around the C4−N1 bond and out-of-plane bending at the N1 atom (τ(C4−N1)=4°, XN =7°, Xc =0.4° ). The amide group plane is nearly coplanar with the phenyl ring. The molecules are connected by two intermolecular hydrogen bonds.