Sofa Form Research Articles

Conformational analysis of 2-isopropyl-5-methyl-5-methoxymethyl-1,3,2-dioxaborinane

Study of conformational transformations of 2-isopropyl-5-methyl-5-methoxymethyl-1,3,2-dioxaborinane using DFT approximation PBE/3ζ and the second order perturbation theory method RI-MP2/λ2 revealed beside the interconversion route sofa–sofa through a transition state corresponding to 2,5-twist form a number of local minima due to internal rotation of isopropyl and methoxymethyl substituents in sofa conformers. Over 88% of the molecules of the studied compound are present in a sofa form with the equatorially oriented CH2OCH3 group.

Conformational analysis of 2,2-dimethyl-5-alkyl-1,3-dioxa-2-silacyclohexanes

Study of conformational isomerization of 2,2-dimethyl-5-alkyl-1,3-dioxa-2-silacyclohexanes using quantum-chemical HF/6-31G(d) and PBE/3z approximations showed that its route involves an equilibrium between the chair conformers with different orientation of substituent at C5 ring atom and proceeds through a transition state corresponding to the 2,5-twist conformation. Molecular dynamics method showed that at room temperature this conformation transforms into the equatorial or axial chair conformers through 1,4-twist or sofa forms. Based on the experimental and theoretical values of vicinal 1H NMR coupling constants we determined quantitative conformational composition of the molecules of these compounds and the values of ΔG0 of the conformational equilibrium.

Etude Conformationnelle De 2,3,5,6,7,8-Hexahydro-4H-Benzopyranne-4-Ones, A L'Aide De La Mecanique Moleculaire

The conformational study of 2,3,5,6,7,8-hexahydro-4H-benzopyran-4-ones, using molecular mechanics, shows that the more stable conformations contain a half-chair cyclohexenic ring and a half-chair strongly distorted toward a sofa form for the dihydropyran-4-one ring. The interconversion barrier of 3,4-dihydro-2H-pyran-4-one is lower than that for cyclohexene (5 versus 6.1 Kcal/mol). This work is ratified by reasonable correlation between experimental data and empirical force-field calculations.

6-Hydroxysalvinolone

The title compound {systematic name: 5,6,10-trihydr­oxy-7-iso­propyl-1,1,4a-trimethyl-2,3,4,4a-tetra­hydro­phenanthren-9(1H)-one}, C20H26O4, is a diterpenoid which was isolated from the roots of Premna obtusifolia. The mol­ecule has three fused six-membered rings; the cyclo­hexane ring is in a twisted-boat conformation and the cyclo­hexene ring adopts a sofa form. Intra­molecular O—H⋯O hydrogen bonds generate two S(5) ring motifs. In the crystal, mol­ecules are linked into infinite one-dimensional chains along the [001] direction by O—H⋯O hydrogen bonds and weak C—H⋯O inter­actions.

7-Acetoxycochinchinone I

The title compound {systematic name: 12-[(2E)-3,7-dimethyl-2,6-octa­dien­yl]-5,8-dihydr­oxy-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one}, C30H32O6, has four fused rings (A/B/C/D) and the xanthone ring system (A/B/C) is essentially planar, with dihedral angles of 1.85 (13) and 2.47 (13)°, respectively, between rings A and B, and between rings B and C. The chromene ring D is in a sofa form. The geranyl side chain is axially attached to ring C with an (−)-synclinal conformation. The 3-methyl-2-butenyl terminal of the geranyl side chain is disordered with the site-occupancy ratio of 0.513 (5):0.487 (5). The acet­oxy group is attached axially to ring A with an (+)-synclinal conformation. An intra­molecular O—H⋯O hydrogen bond involving the carbonyl and hydroxyl groups generates an S(6) ring motif. In the crystal, weak C—H⋯O and C—H⋯π inter­actions, and π–π inter­actions with centroid–centroid distances of 3.6562 (16) and 3.6565 (16) Å are observed.

Routes of conformational isomerization of 4-substituted 1,3,2-dioxaborinanes

With the help of nonempirical quantum-chemical approximations we have studied the conformational equilibria in a series of 4-substituted 1,3,2-dioxaborinanes. It is shown that the route includes minima corresponding to the equatorial and axial sofa forms, and maxima corresponding to the equatorial and axial 2,5-twist conformations.

Nonempirical approach to the conformational analysis of 2,4-dimethyl-1,3,2-dioxaborinane and its oxonium ions

Using nonempirical quantum-chemical approximations RHF//STO-3G, 3-21G, 6-31G(d) and MP2//6-31G(d,p) a conformation isomerism of 2,4-dimethyl-1,3,2-dioxaborinane and its oxonium ions was studied. It was shown that the potential energy surface of the studied molecules has minima corresponding to equatorial (main minimum) and axial sofa forms and maxima corresponding to equatorial and axial conformations of 2,5-twist forms. Calculated values of the barriers of internal rotation of methyl group at the ring C4 atom were found. It was also established that the heat of protonation of the cyclic boric ester was smaller than of the non-boric analog, cis-2,4-dimethyl-1,3-dioxane, owing to decrease in basicity of the oxygen atoms in the cyclic boric ester due to partial double bond character of B-O bond.

Synthesis, Conformation and PKC Isozyme Surrogate Binding of Indolinelactam‐Vs, New Conformationally Restricted Analogues of (‐)‐Indolactam‐V.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis, conformation and PKC isozyme surrogate binding of indolinelactam-Vs, new conformationally restricted analogues of (−)-indolactam-V

New conformationally restricted analogues of tumor promoter (−)-indolactam-V ( 1 ), indolinelactam-Vs ( 8 , 11 ) and their hexyl derivatives at position 1 or 7 ( 9 , 10 , 12 , 13 ), were synthesized from 1 . (3 R)-Indolinelactam-V ( 8 ) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3 S)-indolinelactam-V ( 11 ) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 ( 10 , 13 ) showed binding affinities for C1 domains of protein kinase C (PKC) isozymes compared to 1 , but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3 S)-1-hexylindolinelactam-V ( 12 ) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes.

Ethyl (O–B)-5-(difluoroboryloxy)tricyclo[4.3.1.13,8]undecane-4-carboxylate

The title compound, C14H19BF2O3, can be described as a resonance hybrid. The entering BF2 moiety interacts with the C=O (oxo) groups of the parent compound, 5-(ethoxy­carbonyl)­adamantan-4-one, generating two conjugated double bonds in the six-membered di­fluoro­dioxoborane ring. In spite of the conjugation between the multiple bonds, the tetrahedral configuration of the B atom gives rise to a non-planar conformation of the six-membered ring, which assumes a state intermediate between the boat and sofa forms.

Conformational Composition of 2,5-Disubstituted 1,3,2-Dioxaborinanes

We have used 1H NMR spectra and also MM+ and AM1 calculation methods to show that the conformational equilibrium of 2,5-disubstituted 1,3,2-dioxaborinane molecules, including two sofa forms, is shifted toward the equatorial conformer. We have established the values of ΔG0 for a number of substituents on the C(5) ring atom.

Conformational analysis of cis-Δ1, -Δ2, -Δ3 and -Δ4-tetrahydrophthalic anhydrides by semiempirical and ab initio molecular orbital calculations

Semiempirical and ab initio molecular orbital calculations have been used to study the conformational geometries and the relative stability of the conformers of cis-Δ1, -Δ2, -Δ3 and -Δ4-tetrahydrophthalic anhydrides (THPA). The total energy and the structure of the transition states for the interconversion of conformers were calculated with PM3 semiempirical method. It is found that PM3, AM1 and MNDO semiempirical schemes underestimate the stability of cis-Δ1-THPA, contrary to experimental findings. The ab initio SCF calculations performed at the Restricted Hartree–Fock (RHF) and MP2 levels using effective core pseudo-potential functions with basis sets contracted to 31 split valence (PS-31G) and (PS-31G∗), are in good agreement with the available experimental evidence, e.g. the cis-Δ1-THPA is, thermodynamically, the most stable of all the cis-isomeric anhydrides. The ab initio results indicate that the energy between the conformers changes as a function of the AO basis set. The ground states conformations of cis-Δ1-THPA are increasingly preferred in the more extended basis sets including d-polarized functions on carbon and oxygen atoms. For cis-Δ4-THPA, the folded conformation is calculated to be favored over the open conformation in agreement with the results of NMR analysis of cis-Δ4-tetrahydrophthalic anhydride. The preference of this conformation is also consistent with the crystal structure recently determined by X-ray diffraction technique. The structure analysis of the different conformations at different levels of ab initio calculation, as well as with semiempirical methods, shows that the cyclohexene ring adopts a boat form in cis-Δ4-THPA, a half-chair form in cis-Δ1-THPA and deformed sofa forms in both cis-Δ3-THPA and cis-Δ2-THPA; the anhydride ring being flattened in cis-Δ1-THPA and cis-Δ4-THPA and more twisted in cis-Δ3-THPA and cis-Δ2-THPA. Comparison is made with structures of related compounds.

Triterpenoide. XVII. 3,28-Dimethoxy-3,11,28-trioxo-2,3-seco-18β-olean-12-en-2,9α-olid

The structure of the title compound, C 32 H 46 O 7 , previously derived by spectroscopic methods, is confirmed. Steroidal ring C has a slightly distorted sofa form and all other six-membered rings have a chair conformation. Rings B and C are trans-fused, and rings D and E are cis-fused. The lactone ring has a conformation intermediate between envelope and half-chair.

Triterpenoide. XVI. 2-Formylderivate des Oleanonsäure-methylesters undAllo-betulons

The formylation products of 3-oxo-18β-olean-12-en-28-oic acid methyl ester (oleanonic acid methyl ester) and 19β,28-epoxy-18α-oleanan-3-on (allo-betulon) by the method of Govardhan, Reddy, Ramaiah & Rao [J. Indian Chem. Soc. (1983), pp. 858-860] have the structure of the corresponding methyl 2-formyl-3-hydroxy-18β-olean-2,12-dien-28-oate [C 32 H 48 O 4 , (1b)] and 19β,28-epoxy-3-hydroxy-18α-olean-2-ene-2-carbaldehyde [C 31 H 48 O 3 , (2b)]. These enols are stabilized by short intramolecular O2-H2A…O1 hydrogen bonds between the O atoms of the C3-hydroxy and C31-carbonyl groups and conjugation systems of C3=C2-C31=O1. The enol structure is in agreement with our earlier observation that compounds (1b) and (2b) on treatment with hydroxylamine hydrochloride are not converted into [3,2-c]- but [2,3-d]isoxazoles [Gzella, Linkowska, Zaprutko & Wrzeciono (1999). Acta Cryst. C55, 1031-1034]. Rings A and C in (1b) have a distorted sofa form. The ring A in (2b) has an intermediate conformation between a sofa and half-chair, Ring C in (2b) and rings B, D and E in (1b) and (2b) take the chair conformation. Rings DIE are cis-fused in (1b) and transfused in (2b). The axial 03 and C28 atoms in (2b) are β oriented and form together with the C17, C18 and C19 atoms the five-membered ring F, which has an envelope conformation.

An asatone-type neolignan and its photocage product

The structures of dimethyl 8,8-dimethoxy-7-oxo-1,4-(1,1-dimethoxy-2-oxoethano)-1,4,4a,7,8,8a-hexahydro-naphthalene-2,4a-diyldiacrylate, C 24 H 28 O 10 , (I), and its photocage product, dimethyl 6,6,12,12-tetramethoxy-5,11-dioxotetracyclo[6.2.2.0 3,10 .0 4,9 ]dodecane-2,9-diyl-diacrylate, C 24 H 28 O 10 , (II), were determined in order to investigate the conformational change caused by the intramolecular [2+2] photoreaction. The high efficiency (70%) of the photoreaction of (I) in a 1,4-dioxane solution is attributed to the fact that two C=C double bonds in (I) can become close and parallel to each other simply by changing the configuration of the cyclohexene ring moiety from an envelope to a sofa form. Compound (I) is much less photoreactive in the solid state than in solution.

Triterpenoide. XIV. [2,3-d]Isoxazoltriterpenderivate

The X-ray crystal structure analyses of two triterpene isoxazoles, namely olean-2,12-dieno[2,3-d]isoxazol-28-oic acid methyl ester {methyl isoxazolo[4,5-b]olean-2,12-dien-28-oate, C 32 H 47 NO 3 , (2a)} and 19β,28-epoxy-18α-olean-2-eno[2,3-d]isoxazole {19β,28-epoxy-isoxazolo[4,5-b]-18α-olean-2-ene, C 31 H 47 NO 2 , (4a)} are described. These compounds were obtained by treatment of 2-formyl- or 2-hydroxymethylene derivatives of 3-oxoolean-12-en-28-oic methyl ester, (la) and (1b), and 19β,28-epoxy-18Hα-oleanan-3-one, (3a) and (3b), with hydroxylamine hydrochloride according to the method described by Govardhan, Reddy, Ramaiah & Rao [J. Indian Chem. Soc. (1983), pp. 858-860] for the synthesis of ring-A-fused triterpene [3,2-c]isoxazoles. The structures of the obtained [2,3-d]isoxazoles, (2a) and (4a), were confirmed by the comparison of the bord lengths and bord angles found for the isoxazole rings of compounds (2a) and (4a) with the corresponding data given in the literature. The isoxazole rings in both compounds are planar. Ring A in (2a) and (4a) has a conformation between the half-chair and sofa form. Rings B. D and E in (2a), and B, C, D and E in (4a) have the chair conformation. Ring C in (2a) has a distorted sofa form. In (2a), the rings A/B, B/C and C/D are trans-fused and the rings DIE cis-fused. In (4a), the A/B, B/C, C/D and DIE ring junctions are trans. The axial 02 and C28 atoms in (4a) are β oriented and form, together with the C17. C18 and C19 atoms, the five-membered ring F, which has an envelope conformation.

Twist form of teleocidin derivatives is active in in vivo tumor promotion by (-)-benzolactam-V8-310.

Teleocidin derivatives and the core structure, (-)-indolactam-V ((-)-IL-V), adopt two conformations in solution, the "twist" and the "sofa" forms. (-)-Benzolactam-V8-310 ((-)-BL-V8-310), which specifically adopts the twist form in solution, has been reported to have a significant effect on HL-60 cells and protein kinase C affinity. In this paper, we describe the biological activity with regard to tumor promotion on mouse skin and the wide variety of biological activity of (-)-BL-V8-310 and its derivatives. In both twist and sofa forms (-)-BL-V8-310 inhibited specific 3H-12-O-tetradecanoylphorbol-13-acetate (TPA) binding to a particulate fraction of mouse skin more strongly than (-)-IL-V. The doses for 50% inhibition (IC50) of (-)-IL-V, (-)-BL-V8-310, and teleocidin B-4 were 1000, 400 and 12 nM, respectively. As for the induction of tumor necrosis factor-alpha (TNF-alpha) release into the medium from HL-60 cells, the EC200 values, which are the concentrations of the compound required to achieve 200 pg/ml TNF-alpha in the medium, were 1700, 500 and 19 nM for (-)-IL-V, (-)-BL-V8-310 and teleocidin B-4, respectively. The same amounts (5.5 nmol per application) of (-)-BL-V8-310 and teleocidin B-4, induced tumors on mouse skin initiated with 7,12-dimethylbenz(a)anthracene (DMBA) in 13.3% and 86.7% of tumor-bearing mice, respectively, in week 20. These results confirmed that the twist form of teleocidin derivatives is the active form as far as the induction of biological activity is concerned. Also (-)-BL-V8-310 is a new synthetic tumor promoter designed from data obtained using the receptor cavity model of TPA-type tumor promoters.

Triterpenoide. X. Über neue isomere Triterpenlactone

The X-ray crystal structure analyses of three new triterpene lactones (C29H42O6), namely 9β-hydroxy-28-methoxy-11,28-dioxo-1,2-dinor-10α-18β-olean-12-en-3,10β- olide, (3), its 18α- and 9α,18α-isomers, (4) and (5) [9β-hydroxy-28-methoxy-11,28-dioxo-1,2-dinor-10α-18α-olean-12-en-3,10β- olide and 9α-hydroxy-28-methoxy-11,28-dioxo-1,2-dinor-10α-18α-olean-12-en-3,10β- olide, respectively], are described. Compounds (3)–(5) are obtained by treatment of 3β-hydroxy-11-oxo-18α-olean-12-en-28-oic acid methyl ester, (1), with sodium dichromate in acetic acid. In compounds (3)–(5) the six-membered ring A of (1) is replaced by a γ-lactone ring. In contrast to compound (1), the C25 methyl group at C10 has α configuration. The newly introduced hydroxyl group at C9 is β-oriented in compounds (3) and (4), and α oriented in (5). Ring B in (3) has a boat form, but in (4) and (5) it has different equivalent chair conformations. Ring C in (3) has a sofa form, in (4), it has a slightly distorted half-chair form and in (5), it has a conformation intermediate between the half-chair and sofa forms. Rings D and E have chair conformations in all three compounds and are trans-fused in compounds (4), (5) and (1) and cis-fused in (3). In contrast to compound (1), rings A/B in compounds (3)–(5) and rings B/C in compounds (3) and (4) are cis-fused. In compounds (3)–(5), formation of hydrogen bonds has been observed. Inversion of the α configuration to a β configuration at C18 in oleanolic acid derivatives [transformation of (1) to (3)] has been observed for the first time. The triterpene lactones (3)–(5) are the first known oleanan derivatives with cis-fused A/B [(3)–(5)] and B/C rings [(3) and (4)].

Advanced Computational Docking of Two Teleocidin Congeners to Cys2 Domain of Protein Kinase C.DELTA..

We simulated the docking of two teleocidin congeners to the cys2 domain structure observed in the crystalline complex of protein kinase Cδ with phorbol-13-acetate. The most stable docking models were searched for two conformers of (-)-indolactam-V ((-)-IL-V), twist and sofa form, and for (-)-benzolactam-V ((-)-BL-V8) by using an automatic docking method, ADAM, which can cover all possible binding modes and conformations. The twist form of (-)-IL-V and (-)-BL-V8 molecules fitted well into the same cavity as phorbol-13-acetate. Of the three functional groups hydrogen-bonding to the protein, two hydrogen-bonded with protein atoms in common with phorbol-13-acetate, but the third one hydrogen-bonded with a different protein atom from that in the case of phorbol-13-acetate.

Synthesis, Conformation, and Biological Activity of Teleocidin Mimics, Benzolactams. A Clarification of the Conformational Flexibility Problem in Structure−Activity Studies of Teleocidins

Tumor-promoter teleocidins and their active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states in solution, the twist and sofa form, due to cis−trans isomerization of the amide bond and the steric effects of substituents on the nine-membered lactam ring. Benzolactam-Vs, in which the indole ring of indolactams is replaced with a benzene ring, were designed and synthesized in an attempt to reproduce the active conformation of teleocidins. Among these benzolactams, eight-membered lactams (benzolactam-V8) can only exist in the twist form, and 9- and 10-membered lactams (benzolactam-V9 and -V10) exist exclusively in the sofa form in solution. The stronger biological activity of benzolactam-V-8-310 than that of indolactam-V (IL-V) and the inactivity of benzolactam-V-9-310 for differentiation inducing activity of HL-60 clearly indicated that the twist form is close to the active conformation of teleocidins.