S-cis Configuration Research Articles

Tetraenone A: A New β-Ionone Derivative from Tetraena aegyptia.

In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2S, 5R, 6R, 7E)-2-hydroxy-5,6-dihydro-β-ionone) (1), along with (3S, 5R, 6S, 7E)-3-hydroxy-5,6-epoxy-5,6-dihydro-β-ionone- (2), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside (3), 3β,19α-dihydroxy-ursan-28-oic acid (4), quinovic acid (5), p-coumaric acid (6), and ferulic acid (7), for the first time. The chemical structures of 1-7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with Mpro rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with Mpro to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of Mpro of SARS-CoV-2.

(E)-3-([2,2’-bithiophen]-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one: Synthesis and structural elucidation of chalcone derivatives for potential antioxidant activity

New chalcone derivative was successfully synthesized through Claisen-Schmidt condensation reaction. The XRD study was used to determine the molecular arrangement and it was evident that the enone moiety of the compound adopted s-cis configuration. In crystal packing, the molecules were connected by intermolecular C—H···π and π···π interactions which were then validated via Hirshfeld analysis. The UV-Vis study reveals the absorption wavelength and energy gap of the compound. The DPPH assay showed that the compound exhibited weak antioxidant activity. Molecular docking revealed the binding energy of the compound (6.9 kcal/mol). ADMET study predicted that the compound has a moderate drug-likeness.

Synthesis, structural investigation and computational analysis on a new chalcone derivative: (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(2-chloro-6-fluorophenyl)prop-2-en-1-one

The new chalcone derivative namely, ( E )-1-(benzo[ d ][1,3]dioxol-5-yl)-3-(2‑chloro-6-fluorophenyl)prop‑2-en-1-one (BCFC) was successfully synthesized via Claisen-Schmidt condensation method with a mixture of 2‑chloro-6-fluorobenzaldehyde and 1-(benzo[ d ][1,3]dioxol-5-yl)ethenone. From the single crystal X-ray diffraction analysis, the molecular structure of BCFC shows s-cis configuration with respect to the enone moiety and further stabilized via intramolecular C—H•••F interaction. The planar structure of BCFC further helps to increase the charge transfer within the molecules. There is no significant interaction observed, which is further confirmed by the Hirshfeld fingerprint plot analysis. The optimized molecular structure at the ground state was then calculated by implementing the Density Functional Theory (DFT) method with a B3LYP/6–311 G (d,p) basis set and further reveals the molecular electrostatic potential (MEP) and HOMO–LUMO energy band of BCFC . The red region of the carbonyl group at the enone bridge of BCFC demonstrates the electrophilic attack side and acts as a good acceptor part. In addition, the small HOMO-LUMO energy gap (2.33 eV) shows the suitability of BCFC as a future optoelectronic material. A new halogenated chalcone derivatives have been synthesized and structurally characterized by single crystal XRD and UV–Vis method. The results are compared with the density functional theory (DFT) method with B3LYP/6–311 G ++ (d,p) level. The energies of HOMO LUMO as the energy gaps are calculated for both compounds. The DFT analyses were theoretically computed. The UV–Vis and Hirshfeld surface for the BCFC system are further discussed.

(Trifluorosilyl)methyl 2-methylacrylate: Synthesis, experimental and theoretical studies

The novel stable organosilicon compound containing pentacoordinated silicon atom, named as (trifluorosilyl)methyl 2-methylacrylate, was synthesized and fully characterized including single-crystal X-ray diffraction. The asymmetric unit of the title compound contains two independent molecules, one of which adopting the s-cis configuration and the other has the s-trans configuration with respect to the CO and CC bonds. In the crystal, conformers form cis- and trans-dimeric pairs due to tetrel-bonding interaction and hydrogen bonds CH··· F. Energetic and geometric characteristics for these dimers were calculated by DFT methods at M06-2X/6-311G(d,p) level of theory using QTAIM analysis. The calculations in the polar medium (DMSO) for two dimeric fragments of crystal packing were performed with Onsager self-consistent reaction field method.

Crystal structure of benzyl N'-[(1E,4E)-1,5-bis-(4-meth-oxy-phen-yl)penta-1,4-dien-3-yl-idene]hydrazine-1-carbodi-thio-ate.

In the title hydrazinecarbodi-thio-ate derivative, C27H26N2O2S2, the asymmetric unit is comprised of four mol-ecules (Z = 8 and Z' = 4). The 4-meth-oxy-phenyl rings are slightly twisted away from their attached olefinic double bonds [torsion angles = 5.9 (4)-19.6 (4)°]. The azomethine double bond has an s-trans configuration relative to one of the C=C bonds and an s-cis configuration relative to the other [C=C-C= N = 147.4 (6)-175.7 (2) and 15.3 (3)-37.4 (7)°, respectively]. The torsion angles between the azomethine C=N double bond and hydrazine-1-carbodi-thio-ate moiety indicate only small deviations from planarity, with torsion angles ranging from 0.9 (3) to 6.9 (3)° and from 174.9 (3) to 179.7 (2)°, respectively. The benzyl ring and the methyl-enesulfanyl moiety are almost perpendicular to each other, as indicated by their torsion angles [range 93.7 (3)-114.6 (2)°]. In the crystal, mol-ecules are linked by C-H⋯O, N-H⋯S and C-H⋯π(ring) hydrogen-bonding inter-actions into a three-dimensional network. Structural details of related benzyl hydrazine-1-carbodi-thio-ate are surveyed and compared with those of the title compound.

(E)-1-(Benzo[d][1,3]dioxol-5-yl)-3-([2,2'-bi-thio-phen]-5-yl)prop-2-en-1-one: crystal structure, UV-Vis analysis and theoretical studies of a new π-conjugated chalcone.

In the title compound, C18H12O3S2, synthesized by the Claisen-Schmidt condensation method, the essentially planar chalcone unit adopts an s-cis configuration with respect to the carbonyl group within the ethyl-enic bridge. In the crystal, weak C-H⋯π inter-actions connect the mol-ecules into zigzag chains along the b-axis direction. The mol-ecular structure was optimized geometrically using Density Functional Theory (DFT) calculations at the B3LYP/6-311 G++(d,p) basis set level and compared with the experimental values. Mol-ecular orbital calculations providing electron-density plots of HOMO and LUMO mol-ecular orbitals and mol-ecular electrostatic potentials (MEP) were also computed both with the DFT/B3LYP/6-311 G++(d,p) basis set. The experimental energy gap is 3.18 eV, whereas the theoretical HOMO-LUMO energy gap value is 2.73 eV. Hirshfeld surface analysis was used to further investigate the weak inter-actions present.

Crystal structure, Hirshfeld surface analysis and DFT studies of (E)-1-(4-bromo-phen-yl)-3-(3-fluoro-phen-yl)prop-2-en-1-one.

The asymmetric unit of the title halogenated chalcone derivative, C15H10BrFO, contains two independent mol-ecules, both adopting an s-cis configuration with respect to the C=O and C=C bonds. In the crystal, centrosymmetrically related mol-ecules are linked into dimers via inter-molecular hydrogen bonds, forming rings with R 1 2(6), R 2 2(10) and R 2 2(14) graph-set motifs. The dimers are further connected by C-H⋯O inter-actions into chains parallel to [001]. A Hirshfeld surface analysis suggests that the most significant contribution to the crystal packing is by H⋯H contacts (26.3%). Calculations performed on the optimized structure obtained using density functional theory (DFT) at B3LYP with the 6-311 G++(d,p) basis set reveal that the HOMO-LUMO energy gap is 4.12 eV, indicating the suitability of this crystal for optoelectronic and biological applications. The nucleophilic and electrophilic binding site regions are elucidated using the mol-ecular electrostatic potential (MEP).

Crystal structure and optical spectroscopic analyses of (E)-3-(1H-indol-2-yl)-1-(4-nitro-phen-yl)prop-2-en-1-one hemihydrate.

The asymmetric unit of the title compound, 2C17H12N2O3·H2O comprises two mol-ecules of (E)-3-(1H-indol-2-yl)-1-(4-nitro-phen-yl)prop-2-en-1-one and a water mol-ecule. The main mol-ecule adopts an s-cis configuration with respect to the C=O and C=C bonds. The dihedral angle between the indole ring system and the nitro-substituted benzene ring is 37.64 (16)°. In the crystal, mol-ecules are linked by O--H⋯O and N-H⋯O hydrogen bonds, forming chains along [010]. In addition, weak C-H⋯O, C-H⋯π and π-π inter-actions further link the structure into a three-dimensional network. The optimized structure was generated theoretically via a density functional theory (DFT) approach at the B3LYP/6-311 G++(d,p) basis level and the HOMO-LUMO behaviour was elucidated to determine the energy gap. The obtained values of 2.70 eV (experimental) and 2.80 eV (DFT) are desirable for optoelectronic applications. The inter-molecular inter-actions were qu-anti-fied and analysed using Hirshfeld surface analysis.

Scalable Solution-Phase Synthesis of the Biologically Active Cyclodepsipeptide Destruxin E, a Potent Negative Regulator of Osteoclast Morphology

The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)2PHAL as the chiral ligand, and it was found that the use of the l-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).

Molecular structure, experimental and theoretical1H and13C NMR chemical shift assignment of cyclic and acyclic α,β-unsaturated esters

The experimental 1H and 13C NMR spectra of 13 phenyl cinnamates and four 4-methylcoumarins were investigated and their chemical shifts assigned on the basis of the two-dimensional spectra. For the unsubstituted cinnamic acid phenyl ester, optimized molecular structures were calculated at a B3LYP/6-311++G(d,p) level of theory. 1H and 13C NMR chemical shifts were also calculated with the GIAO method at the B3LYP/6-311 + G(2d,p) level of theory. The comparison between experimental and calculated NMR chemical shift suggests that the experimental spectra are formed from the superposition spectra of the two lowest energy conformers of the compound in solution. The most stable s-cis configuration found in our studies is also the conformation adopted for a related phenyl cinnamate in solid state. The experimental results were analyzed in terms of the substituent effects. Copyright © 2013 John Wiley & Sons, Ltd.

The combined C-H functionalization/Cope rearrangement: discovery and applications in organic synthesis.

The development of methods for the stereoselective functionalization of sp(3) C-H bonds is a challenging undertaking. This Account describes the scope of the combined C-H functionalization/Cope rearrangement (CHCR), a reaction that occurs between rhodium-stabilized vinylcarbenoids and substrates containing allylic C-H bonds. Computational studies have shown that the CHCR reaction is initiated by a hydride transfer to the carbenoid from an allyl site on the substrate, which is then rapidly followed by C-C bond formation between the developing rhodium-bound allyl anion and the allyl cation. In principle, the reaction can proceed through four distinct orientations of the vinylcarbenoid and the approaching substrate. The early examples of the CHCR reaction were all highly diastereoselective, consistent with a reaction proceeding via a chair transition state with the vinylcarbenoid adopting an s-cis conformation. Recent computational studies have revealed that other transition state orientations are energetically accessible, and these results have guided the development of highly stereoselective CHCR reactions that proceed through a boat transition state with the vinylcarbenoid in an s-cis configuration. The CHCR reaction has broad applications in organic synthesis. In some new protocols, the CHCR reaction acts as a surrogate to some of the classic synthetic strategies in organic chemistry. The CHCR reaction has served as a synthetic equivalent of the Michael reaction, the vinylogous Mukaiyama aldol reaction, the tandem Claisen rearrangement/Cope rearrangement, and the tandem aldol reaction/siloxy-Cope rearrangement. In all of these cases, the products are generated with very high diastereocontrol. With a chiral dirhodium tetracarboxylate catalyst such as Rh(2)(S-DOSP)(4) or Rh(2)(S-PTAD)(4), researchers can achieve very high levels of asymmetric induction. Applications of the CHCR reaction include the effective enantiodifferentiation of racemic dihydronaphthalenes and the total synthesis of several natural products: (-)-colombiasin A, (-)-elisapterosin B, and (+)-erogorgiaene. By combining the CHCR reaction into a further cascade sequence, we and other researchers have achieved the asymmetric synthesis of 4-substituted indoles, a new class of monoamine reuptake inhibitors.

Crystal structure and conformational analysis of s-cis-(acetylacetonato)(ethylenediamine-N,N′-diacetato)-chromium(III)

The crystal structure of [Cr(edda)(acac)] (edda = ethylediamine-N,N'-diacetate; acac = acetylacetonato) has been determined by a single crystal X-ray diffraction study at 150 K. The chromium ion is in a distorted octahedral environment coordinated by two N and two O atoms of chelating edda and two O atoms of acac, resulting in s-cis configuration. The complex crystallizes in the space group P2(1)/c of the monoclinic system in a cell of dimensions a = 10.2588(9), b = 15.801(3), c = 8.7015(11) Å, β =101.201(9)° and Z = 4. The mean Cr-N(edda), Cr-O(edda) and Cr-O(acac) bond distances are 2.0829(14), 1.9678(11) and 1.9477(11) Å while the angles O-Cr-O of edda and O-Cr-O of acac are 171.47(5) and 92.72(5)°, respectively. The crystal structure is stabilized by N-H···O hydrogen bonds linking [Cr(edda)(acac)] molecules in distinct linear strands. The visible electronic and IR spectroscopic properties are also discussed. An improved, physically more realistic force field, Vibrationally Optimized Force Field (VOFF), capable of reproducing structural and vibrational properties of [Cr(edda)(acac)] was developed and its transferability demonstrated on selected chromium(III) complexes with similar ligands.

Femtosecond Transient Absorption Spectroscopic Study of a Carbonyl-Containing Carotenoid Analogue, 2-(all-trans-Retinylidene)-indan-1,3-dione

The photophysical properties of a carbonyl-containing carotenoid analogue in an s-cis configuration, relative to the conjugated π system, 2-(all-trans-retinylidene)-indan-1,3-dione (C20Ind), were investigated by femtosecond time-resolved spectroscopy in various solvents. The lifetime of the optically forbidden S(1) state of C20Ind becomes long as solvent polarity increases. This trend is completely opposite to the situation of S(1-ICT) dynamics of carbonyl-containing carotenoids, such as peridinin and fucoxanthin. Excitation energy dependence of the transient absorption measurements shows that the transient absorption spectra in nonpolar solvents were originated from two distinct transient species, while those in polar and protic solvents are due to a single transient species. By referring to the results of MNDO-PSDCI (modified neglect of differential overlap with partial single- and double-configuration interaction) calculations, we conclude: (1) in polar and protic solvents, the S(1) state is generated following excitation up to the S(2) state; (2) in nonpolar solvents, however, both the S(1) and the (1)nπ* states are generated; and (3) C20Ind does not generate the S(1-ICT) state, despite the fact that it has two conjugated carbonyl groups.

(E)-1-[4-(Hexyloxy)phenyl]-3-(3-hydroxyphenyl)prop-2-en-1-one

There are two mol­ecules in the asymmetric unit of the title compound, C21H24O3, in which the dihedral angles between the aromatic rings are 6.4 (1) and 7.0 (1)°. The enone moiety of both mol­ecules adopts an s–cis configuration. In the crystal, inter­molecular O—H⋯O and C—H⋯O inter­actions to the same acceptor O atom generate R 2 1(6) ring motifs and further C—H⋯O inter­actions generate R 2 2(8) ring motifs. Topologically, the R 2 1(6) and R 2 2(8) ring motifs are arranged alternately, forming [001] chains of mol­ecules. The crystal structure is further stabilized by C—H⋯π inter­actions.

(E)-3-(4-Ethoxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one

In the title compound, C17H16O3, the carbonyl group is in an s-cis configuration with respect to the olefinic double bond. The dihedral angle between the two benzene rings is 2.85 (3)°. The prop-2-en-1-one bridge makes dihedral angles of 4.77 (4) and 4.15 (4)°, respectively, with the 2-hy­droxy­phenyl and 4-eth­oxy­phenyl rings. The eth­oxy group is coplanar with the attached phenyl ring [Car—O—C—C = 179.72 (5)°]. An intra­molecular O—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal structure, mol­ecules are stacked in an anti­parallel manner to form columns along the b axis. The columnar structure is stabilized by C—H⋯π inter­actions involving the 2-hy­droxy­phenyl ring.

Conformational Space and Vibrational Spectra of Methyl 4-Chloro-5-phenyl-1,3-oxazole-2-carboxylate

Methyl 4-chloro-5-phenyl-1,3-oxazole-2-carboxylate (MCPOC) has been synthesized and isolated in cryogenic matrices (argon and xenon). FTIR spectroscopy studies on the matrix isolated compound, supported by DFT(B3LYP)/6-311++G(d,p) calculations, allow for the identification of two low-energy conformers (I and II) of the molecule, which differ from each other in the orientation of the ester group relative to the oxazole ring. In both these conformers, the ester moiety is in the s-cis configuration (O horizontal lineC-O-CH(3) dihedral: 0 degrees ). Conformer II is ca. 3.0 kJ mol(-1) higher in energy than form I in the gas phase. Two additional higher energy conformers, III and IV, with relative energies of ca. 30 and 45 kJ mol(-1), respectively, were predicted to exist by the calculations, corresponding to structures where the ester group is in an approximately s-trans arrangement. Annealing of the compound isolated in xenon at 60 K led to aggregation and simultaneous reduction of the population of I compared to that of the more polar conformer II. These results suggest the inversion of the order of stability of the two conformers in that matrix, eventually accompanied by a higher trend of conformer I to aggregate. Full assignment of the observed infrared bands to the two experimentally accessible conformers was carried out for the matrix isolated monomeric species. In addition, the infrared spectra of the neat compound in the low-temperature (10 K) amorphous and crystalline phases, as well as the infrared and Raman spectra of the crystal at room temperature were also obtained and assigned.

(E)-1-(4-Decyloxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one

In the title compound, C25H32O3, the asymmetric unit contains two crystallographically independent mol­ecules: both enone groups adopt an s-cis configuration. In the crystal, O—H⋯O and C—H⋯O inter­molecular inter­actions form bifurcated hydrogen bonds, which generate R 1 2(6) ring motifs. These inter­molecular inter­actions link the mol­ecules into one-dimensional chains along the [10] direction. The crystal structure is further stabilized by C—H⋯π inter­actions.

(E)-3-(2,3-Dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one

The mol­ecular conformation of the title compound, C18H18O5, is stabilized by a strong intra­molecular hydrogen bond between the hydroxyl and carbonyl groups. The C=C double bond displays an E configuration while the carbonyl group shows an S-cis configuration relative to the double bond. The dihedral angle between the two rings is 15.0 (1)°.

(E)-(25S)-23-Acetyl-5β-furost-22-ene-3β,26-diol

The title steroid, C29H46O4, is a furostene derivative with a C=C double-bond length of 1.353 (3) Å and an E configuration. The side chain is oriented toward the α face of the A–E steroidal nucleus and presents a disordered terminal CH2—OH group [occupancies for resolved sites are 0.591 (9) and 0.409 (9)]. The methyl group at C20 attached to ring E is also oriented toward the α face, avoiding steric hindrance with the carbonyl O atom of the acetyl group. The furostene and acetyl functionalities form an α,β-unsaturated ketone system, with an s-cis configuration. All hydr­oxy and carbonyl groups are involved in weak inter­molecular hydrogen bonds. The absolute configuration was assigned from the synthesis.

UVA Self‐Photosensitized Oxygenation of β‐Ionone

The steady-state UVA (350 nm) photolysis of (E)-beta-ionone (1) in aerated toluene solutions was studied by (1)H NMR spectroscopy. The formation of the 1,2,4-trioxane (2) and 5,8-endoperoxide (5) derivatives in the ratio of 4:1 was observed. Time-resolved laser induced experiments at 355 nm, such as laser-flash photolysis, photoacoustic and singlet oxygen (1)O(2) phosphorescence detection, confirmed the formation of the excited triplet state of 1 with a quantum yield Phi(T) = 0.50 as the precursor for the generation of singlet oxygen (1)O(2) (Phi(Delta) = 0.16) and the isomeric alpha-pyran derivative (3), which was a reaction intermediate detected by NMR. In turn, the reaction of (1)O(2) with 1 and 3 occurred with rate constants of 1.0 x 10(6) and 2.5 x 10(8) M(-1)s(-1) to yield the oxygenated products 5 and 2, respectively, indicating the relevance of the fixed s-cis configuration in the alpha-pyran ring in the concerted [2+4] cycloaddition of (1)O(2).