Chiroptical Data Research Articles

Total synthesis of the marine sponge metabolites (+)-rottnestol, (+)-raspailol A and (+)-raspailol B.

The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.

Cyclorocaglamide, the first bridged cyclopentatetrahydrobenzofuran, and a related "open chain" rocaglamide derivative from Aglaia oligophylla.

Two rocaglamide-related natural products, the previously known compound 6-demethoxy-10-hydroxy-11-methoxy-6,7-methylendioxyrocaglamide (3), and cyclorocaglamide (4), its 8b,10-anhydro analogue, have been isolated from the tropical plant Aglaia oligophylla. Compound 4 is the first bridged cyclopentatetrahydrobenzofuran natural product, and it exhibited a CD spectrum virtually opposite that of all the other rocaglamide natural products known so far, but it still has the same absolute configuration at all stereogenic centers of the basic molecular framework. This was shown unequivocally by quantum chemical CD calculations (here based on molecular dynamics-weighted force field structures) and was finally confirmed experimentally, by a "biomimetic-type" cyclization of 3 to give 4, with the expected "inversion" of the CD spectrum. The opposite chiroptical properties of 3 and 4, despite their homochiral character, underline the necessity of handling chiroptical data with the greatest care, e.g., by simulating them by quantum chemical CD calculations. Compound 3 exhibited an LC(50) of 2.5 ppm when evaluated against neonate larvae of Spodoptera littoralis, while 4 was inactive in this assay up to 100 ppm.

Hydrobenzoin-based rigid chiral polymer.

We prepared a rigid, chiral polymer (1) from optically active hydrobenzoin-based subunits. Nonracemic monomer units 6 and 8 were prepared by asymmetric dihydroxylation (AD) methodology and polymerization was carried out under Sonagashira coupling conditions. Polymer 1 was obtained in good yield with a molecular weight M(n) = 5,100 (PDI = 2.3). Modeling suggests that polymer 1 could form a stable helical mainchain conformation in solution or the solid state. The chiroptical data of the polymer and a low-molecular weight model compound (9) are compared.

Inherent chirality of the retinal chromophore in rhodopsin—A nonempirical theoretical analysis of chiroptical data

Inherent chirality of the retinal chromophore in rhodopsin—A nonempirical theoretical analysis of chiroptical data

Synthesis and Chiroptical Analysis of Optically Active Chiral Shell Dendrons

We have prepared a series of chiral dendrons (1-4) in which chiral subunits are placed in individual generational shells at varying distances from the focal point. The optical activity of these chiral dendritic structures is successfully modeled using structurally similar low-molecular weight model compounds. In dendrons 1a and 1b a chiral subunit is directly adjacent to the focal point, whereas in dendrons 2, 3, and 4a,b the chiral subunits are incorporated in the interior of the dendron. A marked difference in optical activity between the former 1a and 1b) and latter (2, 3, 4a,b) dendrons is mirrored in the optical activities of model compounds 12a, 12b, 19a, and 19b. These model compounds directly mimic the surrounding constitution of the chiral subunits in the dendrons. This successful analysis of the chiroptical data using low-molecular weight model compounds suggests that these dendrons do not possess conformational order in solution.

Determination of the absolute configuration of (-)-(3R)-O-beta-D-glucopyranosyloxy-5-phenylpentanoic acid from Polygonum salicifolium.

The absolute configuration of the title compound has been determined after its enzymatic hydrolysis to 3-hydroxy-5-phenylpentanoic acid, esterification, and identification of the enantiomerically pure methyl (3R)-hydroxy-5-phenylpentanoate by HPLC on Chiralcel(R)OD-H. For reasons of inconsistent literature data, enantioselective reductions of methyl 3-oxo-5-phenylpentanoate have been reinspected and the stereochemical outcome unequivocally confirmed by both chiroptical and HPLC retention data.

Absolute configuration of a diaryldiacyloxy spiroselenurane and resolution of a carbon analog

The enantiomers of 3,3′-spirobi(3-selenaphthalide) (2) were obtained via direct separation by liquid chromatography on a chiral stationary phase. Determination of the absolute configuration was made by X-ray crystallography with the use of the anomalous dispersion technique. The first eluted (+)-form (λ = 302 and 365 nm) of 2 was found to have (S)-configuration. By a comparison of CD-spectra, the same (S)-configuration could be assigned to the (+)-forms of the sulfur (1) and tellurium (7) analogs of 2. An asymmetric dichloro-substituted spirobilactone (4) was also synthesized and separated into its enantiomers. Relative configurations between 4 and its parent compound (3) were established from the corresponding chiroptical data obtained. Chirality 12: 71–75, 2000. © 2000 Wiley-Liss, Inc.

Inherent chirality of the retinal chromophore in rhodopsin-A nonempirical theoretical analysis of chiroptical data.

CASSCF and GAUSSIAN CIS calculations were performed on ground and excited states of different conformations of 11-cis-retinal protonated Schiff bases, the chromophore of rhodopsin, in order to study their chiroptical properties and attempt a correlation between absolute conformation and CD-spectral data. Geometries were taken from molecular models, from published rhodopsin models, and from retinal conformations obtained from molecular dynamics with geometry restraints. In all the cases studied we find that a positive sense of twist about the C12-C13 bond correlates with a calculated positive CD of the long wavelength absorption band; the twist of the C6-C7 bond modulates this primary contribution of the C12-C13 bond. The correlation of the beta-band with structural features is not straightforward. Calculations on bathorhodopsin lend support to the idea that this intermediate is a highly twisted all-trans-conformation.

Absolute configuration of a diaryldiacyloxy spiroselenurane and resolution of a carbon analog.

The enantiomers of 3,3'-spirobi(3-selenaphthalide) (2) were obtained via direct separation by liquid chromatography on a chiral stationary phase. Determination of the absolute configuration was made by X-ray crystallography with the use of the anomalous dispersion technique. The first eluted (+)-form (lambda = 302 and 365 nm) of 2 was found to have (S)-configuration. By a comparison of CD-spectra, the same (S)-configuration could be assigned to the (+)-forms of the sulfur (1) and tellurium (7) analogs of 2. An asymmetric dichloro-substituted spirobilactone (4) was also synthesized and separated into its enantiomers. Relative configurations between 4 and its parent compound (3) were established from the corresponding chiroptical data obtained. Chirality 12: 71-75, 2000.

Absolute Sense of Twist of the C12-C13 Bond of the Retinal Chromophore in Rhodopsin—Semiempirical and Nonempirical Calculations of Chiroptical Data

The sign of the dihedral angle of the 12-s-trans bonds in the protonated Schiff base of 11-cis-retinal (see picture on the right) correlates with the sign of the long-wavelength absorption in the circular dichroism spectra. This is the result of the high-quality excited-state calculations on the chromophore of the visual pigment rhodopsin.

Synthesis of optically active chiral shell dendrons

We present the preparation of a series of chiral dendrons, in which chiral subunits are placed in individual generational shells at increasing distances from the focal point, by a combination of convergent and divergent dendrimer synthesis methods. Analysis of chiroptical data suggests that these dendrons do not possess conformational order in solution.

Constitution, Configuration, and the Optical Activity of Chiral Dendrimers

Three series of zeroth to second generation chiral dendrimers, 7−9, 10−12, and 13−15, were prepared by convergent methods using chiral, nonracemic AB2 monomers 1, 2, and 3, respectively. Chiroptical data revealed a significant change in molar rotation per subunit ([Φ]D/n) as dendrimer generation increased for dendrimers 7−9 and 10−12, but not for dendrimers 13−15, a possible indication of chiral conformational order in the former two series of dendrimers, but not in the last. However, the optical activities ([Φ]D) of low-molecular-weight model compounds 16 (+262) and 17 (+122), prepared to simulate different regions of the dendrimer structure, suggest that as generation size increases slight constitutional changes have a strong effect on the chiroptical properties of the dendrimer subunits. Using the [Φ]D values of these and other (18−23) low-molecular-weight model compounds, we calculated [Φ]D values for dendrimers 7−15 that agree within 14% of the observed values. Agreement between the optical activity ...

C45‐ and C50‐Carotehoids. Part 8. Synthesis of (all‐E,2S,2′S)‐bacterioruberin, (all‐E,2S,2′S)‐monoanhydrobacterioruberin, (all‐E,2S,2′S)‐bisanhydrobacterioruberin, (all‐ E,2R,2′R)‐3,4,3′,4′‐tetrahydrobisanhydro‐ bacterioruberin, and (all‐E,S)‐2‐isopentenyl‐3,4‐dehydrorhodopin

AbstractStarting from (R)‐3‐hydroxybutyric acid ((R)‐10) the C45‐ and C50‐carotenoids (all‐E,2S,2′S)‐bacterioruberm (1), (all‐E,2S,2′S)‐monoanhydrobacterioruberin (2), (all‐E,2S,2′S)‐bisanhydrobacterioruberin (3), (all‐E,2R,2′R)‐3,4,3′,4′‐tetrahydrobisanhydrobacterioruberin (5), and (all‐E,S)‐2‐isopentenyl‐3,4‐dehydrorhodopin (6) were synthesized. By comparison of the chiroptical data of the natural and the synthetic compounds, the (2S)‐ and (2′S)‐configuration of the natural products 1–3 and 6 was established.

Helically twisted chiral cyanine dyes: Influence of chromophore length on observed and calculated rotatory strengths

Synthesis, chiroptical properties, and quantum-mechanical calculations of the monomethine dye 3 and of the trimethine dyes 7 and 11 are reported. In 3 and 11, the chromophore is forced into a twisted all-Z-conformation by steric interaction of the end groups in the former and the presence of a t-butyl group in the mesoposition of the latter, which is manifest in the UV/Vis spectra not only in the reduced intensity of the longest wavelength absorption, but also in the occurrence, at shorter wavelength, of a “cis-peak.” Chiral substitution of the end groups serves as chiral anchor to discriminate between otherwise enantiomeric forms and makes them amenable to chiroptical investigation. The results are in agreement with theoretically calculated chiroptical data based on helically twisted cyanine chromophores. They support the contention that not only the sense of the helix, but also its length determines the sign of the associated Cotton effect. Chirality 9:243–249, 1997. © 1997 Wiley-Liss, Inc.

Helically twisted chiral cyanine dyes: Influence of chromophore length on observed and calculated rotatory strengths

Synthesis, chiroptical properties, and quantum-mechanical calculations of the monomethine dye 3 and of the trimethine dyes 7 and 11 are reported. In 3 and 11, the chromophore is forced into a twisted all-Z-conformation by steric interaction of the end groups in the former and the presence of a t-butyl group in the mesoposition of the latter, which is manifest in the UV/Vis spectra not only in the reduced intensity of the longest wavelength absorption, but also in the occurrence, at shorter wavelength, of a “cis-peak.” Chiral substitution of the end groups serves as chiral anchor to discriminate between otherwise enantiomeric forms and makes them amenable to chiroptical investigation. The results are in agreement with theoretically calculated chiroptical data based on helically twisted cyanine chromophores. They support the contention that not only the sense of the helix, but also its length determines the sign of the associated Cotton effect. Chirality 9:243–249, 1997. © 1997 Wiley-Liss, Inc.

Glucoindole Alkaloids from Stem Bark ofStrychnos mellodora

Three glucoindole alkaloids, dolichantoside (1), strictosidine (2), and palicoside (3), have been identified in the stem bark of Strychnos mellodora (Loganiaceae), collected in Zimbabwe. The chiroptical (CD) data are compared.

Absorption, emission, and chiroptical spectra of neurokinin 1 tachykinin receptor antagonists: the role of charge-transfer states on the biological activity.

A spectroscopic investigation, based on both electronic absorption and emission spectra as well as on chiroptical data, was performed on novel neurokinin 1 (NK1) tachykinin receptor antagonists, exhibiting interesting biological activity. These pseudopeptides have two fluorophores, i.e. indole (I) and naphthalene (N), and a central scaffold with different conformational mobility. Absorption spectra in methanol show the presence of a new band with respect to the sum spectrum of the isolated chromophores at around 285 nm, the intensity of which linearly increases as the bioactivity increases. This absorption disappears by using dioxane as solvent. It is ascribed to an intramolecular I-N charge-transfer (CT) complex that forms to different extent, depending on the flexibility of the scaffold. Under this condition, the molecules fold and apparently attain the correct conformation for competing substance P binding to the NK1 receptor, lending plausibility to the role of dipolar charged, spatially close aromatic moieties as topochemical elements in the mechanism of action of substance P antagonists. The excited-behavior parallels that in the ground state, as the quenching of the singlet state at 340 nm is found to be linearly dependent on the biological activity, too. Upon decreasing solvent polarity (methanol vs dioxane) the emissions of the dipolar state at around 370 nm disappears, while exciplex emission in the range of 400-500 nm occurs. This transition from charge-separated to exciplex-like states by lowering the dielectric constant of the medium very likely reflects a change in the structural features of the intramolecular I-N stacked complex, from a twisted or an asymmetrically overlapped conformation of the indolyl and naphthyl rings to a face-to-face geometry. Implications of the rigidity of the molecules, arising from the formation of the intramolecular CT complex, on the ellipticity are briefly discussed.

Synthesis and thermal reorganisations of iminoaziridines. Ab initio calculations of their transition states, of diazatrimethylenemethanes, and some cyclic members of the C2H4N2 potential‐energy hypersurface

Abstract2‐Iminoaziridine 19 and the pairs of isomers 22/23 and 32/33 can be obtained in high yields by base‐induced 1,3‐dehydro‐halogenation of the corresponding α‐halo amidines. Regio‐selectivity of the ring closure reaction of 21 is achieved by treatment with potassium hydride as base in the presence of 18‐crown‐6 to afford almost exclusively 23. At low temperatures, the cyclisation of 21a under the influence of potassium tert‐butoxide occurs diastereoselectively yielding (Z)‐22 and (Z)‐23 (87:13). Resolution of racemic 21a can be attained by single recrystallisation of the nicely crystallised mandelates of the like configuration, thus providing an efficient route to (R)‐ and (S)‐23 of high enantiomeric purity. Chiroptical data are reported for 21a and 23. – (E)‐ and (Z)‐22 equilibrate faster by more than one order of magnitude than (E)‐ and (Z)‐23 but almost the same preference for the E diastereomer is found in both cases. – Only first‐order decomposition into isocyanides 6 and imines is observed on thermolysis of 19, 22, 23, and 32 with activation parameters depending on the substitution pattern. In contrast, the thermal valence isomerisation 35 → 36 is fast enough to compete with the [2 + 1] cycloreversion of 35. Thermal racemisation of (R)‐23 does not occur.Quantum‐chemical calculations were performed on the parent iminoaziridines (E)‐ and (Z)‐38, 3‐amino‐2H‐azirine (39), the methylenediaziridines cis‐ and trans‐40, and diastereomeric closed‐shell and open‐shell planar (41) and (open‐shell) „mono‐orthogonal”︁ diazatrimethylenemethanes 42, 43. Complete geometry optimisations were appropriately performed with the RHF/6‐31 + G** and the UHF/6‐31 + G** basis sets. Energies of the closed‐shell states were calculated on the RHF, MP2, MP4SDTQ, and CCSD(T) levels, those of open‐shell states on the UHF, UMP2, UMP4SDTQ, and CCSD(T)/UHF levels. – (E)‐38, being lowest in energy of the parent iminoaziridines (Erel = 0.0), equilibrates with (Z)‐38 via an almost linear transition state (Erel = 113.4 kJ mol−1) and decomposes into hydrogen isocyanide and formaldimine in a one‐step cheletropic process [Erel = 179.8 kJ mol‐1, CCSD(T)/RHF] with a highly unsymmetrical transition state in which the N1–C2 bond is almost completely broken whereas the C2–C3 bond is still strong. The same is true for the cheletropic decomposition of (Z)‐38 the transition state of which (Erel = 168.2 kJ mol−1) is even lower by 11.6 kJ mol−1. – Energy‐rich zwitterionic transition states are found with the RHF method among which 1A′‐(E,Z)‐41 is lowest in energy [Erel = 203.0 kJ mol−1, CCSDT(T)]. Planar singlet (= transition states of CN‐bond rotation) and triplet diazatri‐methylenemethane diradicals possess energies in the range of Erel = 140–160 and 100–120 kJ mol−1 [CCSD(T)], respectively. Complete UHF optimisation of the singlet structures without symmetry constraint yielded five minima 42, 43 of mono‐orthogonal geometry with similar or slightly lower energies than the planar UHF singlets. In the transition state of the valence isomerisation of (E)‐38 [Erel = 170 kJmol−1, CCSD(T)/UHF], the N1–C3 bond is elongated while the plane of the methylene group is still orthogonal to the C(2) = NH plane. An activation energy of (185 ± 20 kJmol−1) is estimated for ring opening of 38 involving species with high diradical character.

Circular dichroism spectra of tricarbonyliron π-complexes

A number of optically active tricarbonyliron π-complexes with unsymmetrical cyclohexadiene and cyclohexadienyl ligands have been prepared from diols available by the oxidation of arenes by Pseudomonas putida. The circular dichroism spectra of the metal complexes provide an empirical guide for the assignment of absolute configuration from chiroptical data for this class of compounds.

Conformation in the Solid State and in Solution of 3,3′(4H,4′H)‐Spirobi[2H‐1,5‐benzodioxepin

AbstractThe “spiro‐coplanar” conformation of 6,6′‐methoxycarbonyl‐3,3′(4H,4′H)‐spirobi[2H‐1,5‐benzodioxepin] (1b) and the 3P configuration of the corresponding menthol ester 1c have been determined from chiroptical data by application of the exciton theory. The solid‐state conformation of the central part of the menthol ester molecule is “spiro‐coplanar”, too, with nearly D2 symmetry. The menthol moieties have chair conformations, and the absolute configurations at their chiral centers have been assigned using enantiomer‐sensitive Bijvoet pairs; they are in agreement with the known absolute configuration of menthol.