Systematic Assignment of the Configuration of Flexible Natural Products by Spectroscopic and Computational Methods:  The Bistramide C Analysis

Zuber, Gérard; Goldsmith, Michael‐Rock; Hopkins, Tamara D.; Beratan, David N.; Wipf, Peter

doi:10.1021/ol052154v

Cited by 30 publications

(27 citation statements)

References 34 publications

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“…cxviii The benefits of the superpositions of molar rotations are obvious: none of the original material was required for chemical conversions for the assignment of configuration. The disadvantage is the necessity of synthesis of fairly advanced intermediates and, of course, accurately reported [α] D for natural product free of strongly rotating contaminants.…”

Section: Selected Examplesmentioning

confidence: 99%

Integrated approaches to the configurational assignment of marine natural products

Molinski

Morinaka

2012

Tetrahedron

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Section: Selected Examplesmentioning

confidence: 99%

Integrated approaches to the configurational assignment of marine natural products

Molinski

Morinaka

2012

Tetrahedron

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“…Subsequently, we also combined the use of NMR NOEs, chemical shifts, and J -coupling measurements with experimental and computational OR and ECD data to determine the AC of the marine natural product bistramide C (Figure 1). 16 This study demonstrated that the judicious use of electronic structure analysis and spectroscopic data enabled a successful AC assignment even of a large and conformationally flexible natural product with multiple unassigned stereocenters. Other groups have also noted the utility of applying multiple chiroptical methods (including ORD, ECD, VCD, and ROA) to determine AC 17…”

Section: Probing Molecular Dissymmetry Using Chiroptical Spectroscopymentioning

confidence: 86%

Optical Signatures of Molecular Dissymmetry: Combining Theory with Experiments To Address Stereochemical Puzzles

2009

Self Cite

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ConspectusModern chemistry emerged from the quest to describe the three-dimensional structure of molecules: van't Hoff's tetravalent carbon placed symmetry and dissymmetry at the heart of chemistry. In this Account, we explore how modern theory, synthesis, and spectroscopy can be used in concert to elucidate the symmetry and dissymmetry of molecules and their assemblies. Chiroptical spectroscopy -including optical rotatory dispersion (ORD), electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA)-measures the response of dissymmetric structures to electromagnetic radiation. This response can in turn reveal the arrangement of atoms in space, but deciphering the molecular information encoded in chiroptical spectra requires an effective theoretical approach. Although important correlations between ECD and molecular stereochemistry have existed for some time, a battery of accurate new theoretical methods that link a much wider range of chiroptical spectroscopies to structure have emerged over the last decade. The promise of this field is considerable: theory and spectroscopy can assist in assigning the relative and absolute configurations of complex products, in revealing the structure of non-covalent aggregates, in defining metrics for molecular diversity based upon polarization response, and in designing chirally imprinted nanomaterials. The physical organic chemistry of chirality is fascinating in its own right: defining atomic and group contributions to optical rotation (OR) is now possible. Although the common expectation is that chiroptical response is determined solely by a chiral solute's electronic structure in a given environment, chiral imprinting effects on the surrounding medium and molecular assembly can, in fact, dominate the chiroptical signatures.The theoretical interpretation of chiroptical markers is challenging because the optical properties are subtle, which results from the strong electric dipole and the weaker electric quadrupole and magnetic dipole perturbations of the electromagnetic field. Moreover, OR arises from a combination of nearly canceling contributions to the electronic response. Indeed, the challenge posed by the chiroptical properties delayed the advent of even qualitatively accurate descriptions for some chiroptical signatures until the last decade when, for example, prediction of the observed sign of experimental OR became accessible to theory.The computation of chiroptical signatures, in close coordination with synthesis and spectroscopy, provides a powerful framework to diagnose and to interpret the dissymmetry of chemical structures and molecular assemblies. Chiroptical theory now produces new schemes to elucidate structure, to describe the specific molecular sources of chiroptical signatures, and to assist in our understanding of how dissymmetry is templated and propagated in the condensed phase.E-mails: E-mail: david.beratan@duke.edu; E-mail: pwipf@pitt.edu. 3 Success in assigning the absolute configuration of small molecu...

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“…In spite of all these progresses, some difficulties are still present. In fact, Stephens et al18 claiming that the ab initio calculation of the OR (and of ECD) provides a reliable answer only by the use of TDDFT method with extended basis sets (i.e., including diffuse functions) propose the use of the TDDFT method with the state‐of‐the‐art hybrid functional B3LYP19–21 and an extended basis set (aug‐cc‐pVDZ or higher) as a reliable and largely applicable22–57 calculation technique. Clearly, such a recipe makes compulsory the use of powerful computing systems when big‐sized molecules (i.e., those having applicative interest and most common for the practicing organic chemist) are treated: this represents a clear obstacle to the diffusion of these methods among nonspecialists.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, chiroptical properties, and their theoretical simulation of some highly rotating benzotricamphor derivatives

Mazzeo¹,

Giorgio²,

Rosini³

et al. 2009

Chirality

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The large molecules 1-3 (69, 90, and 102 atoms, respectively), prepared by cyclotrimerization of enantiomerically pure derivatives of (2)-bornyl acetate, show intense ECD spectra, high optical rotation (OR) values (200-1300, in absolute value) dominated in sign and order of magnitude by the lowest-energy Cotton effects, that is, they are the ideal candidates to test the reliability of our ''approximate'' (TDDFT/B3LYP/6-31G* or smaller basis set) approach to the calculation of chiroptical properties. As a matter of fact, a correct simulation of the OR values and ECD spectra of 1 and 2 can be obtained even using STO-3G basis set and semiempirical or molecular mechanics input geometries: for 1, at the TDDFT/B3LYP/STO-3G level, the OR values are of the order of 500-550, versus an experimental value ranging between 660 and 690, depending on the solvent. On the contrary, the case of 3 (exp. OR between 21330 and 21500) is really complex (for instance, the OR values range between 23216 and 2729 (TDDFT/B3LYP/6-31G* calculations) or 21824 and 2444 (TDDFT/B3LYP/STO-3G calculations)), making the comparison between calculated and experimental values more difficult. The behavior of 3 is due to its molecular flexibility, whereas 1 is a really rigid molecules and 2 behaves (vide infra) as it were a rigid system. These observations strongly indicate that the conformational freedom constitutes one of the major difficulties for a correct but simple simulation of the chiroptical properties.

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Systematic Assignment of the Configuration of Flexible Natural Products by Spectroscopic and Computational Methods: The Bistramide C Analysis

Cited by 30 publications

References 34 publications

Integrated approaches to the configurational assignment of marine natural products

Integrated approaches to the configurational assignment of marine natural products

Optical Signatures of Molecular Dissymmetry: Combining Theory with Experiments To Address Stereochemical Puzzles

Synthesis, chiroptical properties, and their theoretical simulation of some highly rotating benzotricamphor derivatives

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