Diastereoselective Synthesis of Alkylated 1,4-Cyclohexadiene Esters Using Epimeric Pyrroloimidazolones

Synthesis ◽  
2020 ◽  
Vol 53 (01) ◽  
pp. 182-192
Author(s):  
Costa Metallinos ◽  
Ngan Tran ◽  
Dusty Cadwallader
Keyword(s):  
Methoxy Group ◽  
Specific Rotation ◽  
Chiral Center ◽  
Cope Rearrangement ◽  
Diastereoselective Synthesis ◽  
Reductive Alkylation ◽  
Birch Reduction ◽  
X Ray ◽  
X Ray Crystallography

A pair of ortho-benzoate esters containing epimeric pyrroloimidazolones undergo sequential Birch reduction and diastereoselective alkylation to provide products ranging from 88:12 to >95:5 diastereomeric ratio (dr) for the syn-epimer, and 50:50 to 95:5 dr for the anti-epimer. The stereochemistry of the products is confirmed by a combination of X-ray crystallography on a key anti-epimer-derived product, in combination with specific rotation measurements of enantiomers that are prepared from the syn or anti starting materials. A diastereomerically pure allyl-substituted substrate is shown to undergo Cope rearrangement, which transposes the quaternary chiral center to a remote position without racemization. This work is complementary to asymmetric reductive alkylation reported previously by Schultz using anisole substrates with chiral benzamide auxiliaries in that the pyrroloimidazolones act as surrogates for the methoxy group.

Novel Synthesis, Molecular Structure, and Theoretical Studies of Dispiro Compounds via Pseudo-eight-component Reaction

2014 ◽  
Vol 67 (11) ◽  
pp. 1656 ◽  
Author(s):  
Nourallah Hazeri ◽  
Mojtaba Lashkari ◽  
Santiago García-Granda ◽  
Laura Torre-Fernández
Keyword(s):  
Diels Alder ◽  
Quantum Mechanical ◽  
Theoretical Studies ◽  
Diastereoselective Synthesis ◽  
One Pot ◽  
X Ray ◽  
Complex Products ◽  
X Ray Crystallography ◽  
Novel Synthesis ◽  
The Stability

We have developed a diastereoselective synthesis of dispiro compounds through a one-pot domino pseudo-eight-component reaction of amines, aldehydes, and Meldrum’s acid. This method resulted in the generation of complex products with four stereocentres and involves formation of 10 new bonds. Quantum mechanical calculations were undertaken in order to determine the stability of the eight diastereomer structures of compound 4a. The crystal structure of 4k was determined by X-ray crystallography. Reaction mechanism can proceed through Knoevenagel, Aldol condensations, Diels-Alder cycloaddition, and Michael addition.

Spirocyclization of Isatin with Chiral α-Aminothiols: Diastereoselective Synthesis of (-)- and (+)-4'-(Methoxycarbonyl)spiro[indoline-3,2'-thiazolidin]-2-one

2000 ◽  
Vol 65 (3) ◽  
pp. 425-433 ◽  
Author(s):  
Peter Kutschy ◽  
Mojmír Suchý ◽  
Milan Dzurilla ◽  
Pavel Pazdera ◽  
Mitsuo Takasugi ◽  
...  
Keyword(s):  
Spectral Methods ◽  
Room Temperature ◽  
Side Product ◽  
Diastereoselective Synthesis ◽  
Reaction Conditions ◽  
Decomposition Products ◽  
X Ray ◽  
X Ray Crystallography

Reactions of isatin with chiral α-aminothiols have been studied. With L-cysteine, only decomposition products were formed under various reaction conditions, whereas D- and L-penicillamine afforded mixtures of diastereomeric 4'-carboxy-5',5'-dimethylspiro[indoline- 3,2'-thiazolidin]-2-ones (4a and 4b or 5a and 5b) in the ratio 1 : 1. The reaction of isatin with methyl L- and D-cysteinates under mild reaction conditions (methanol-benzene, room temperature) proceeded diastereoselectively with the formation of (-)- and (+)-4'-(methoxycarbonyl)spiro[indoline-3,2'-thiazolidin]-2-one (6a and 8) in 38 and 30% yields, respectively. Optically inactive 4'-(methoxycarbonyl)spiro[indoline-3,2'-([2',5']dihydrothiazol)]-2-one (7) was isolated as a side product in 7 and 3% yield, respectively. Structure of the obtained products was determined by spectral methods, including NOE difference measurements and by X-ray crystallography.

Steric effects in the diastereoselective reduction of β-ketosulfones

1988 ◽  
Vol 66 (11) ◽  
pp. 2860-2869 ◽  
Author(s):  
J. Stuart Grossert ◽  
H. Ranjith W. Dharmaratne ◽  
T. Stanley Cameron ◽  
Beverly R. Vincent
Keyword(s):  
Solid State ◽  
Chiral Center ◽  
Nucleophilic Attack ◽  
Resonance Spectroscopy ◽  
Reaction Conditions ◽  
X Ray ◽  
X Ray Crystallography ◽  
Sodium Borohydride Reduction ◽  
Diastereoselective Reduction ◽  
Reduction Of Ketones

The stereochemical course of the reduction of ketones adjacent to a chiral center normally shows some diastereoselectivity (described by Cram's rule), the degree of which is dependent on the structure of the ketone and on the reaction conditions; the selectivity in acyclic species is often not very great. In this paper, we describe the sodium borohydride reduction of four acyclic β-ketosulfones, containing a chiral center at the α position, in which the products are formed with high diastereoselectivity. Reasons for this selectivity became apparent when we were able to show that these ketosulfones apparently exist predominantly in the same conformation in solution as in the solid state. This conformation requires that the preferred trajectory for nucleophilic attack on the carbonyl group leads to reaction on the re face, to yield the threo diastereomer of the β-hydroxysulfone. The results that led to these conclusions were obtained from structural studies by X-ray crystallography, as well as by detailed 1H and 13C nuclear magnetic resonance spectroscopy. In some cases, the latter spectra were run both in solution and in the solid state.

Difference Fourier Analysis of Glucose Embedded and Frozen Hydrated Purple Membrane

1982 ◽  
Vol 40 ◽  
pp. 74-75
Author(s):  
Jules S. Jaffe ◽  
Robert M. Glaeser
Keyword(s):  
Purple Membrane ◽  
Data Set ◽  
High Resolution Data ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fourier Techniques ◽  
Versus Protein ◽  
The Difference ◽  
Difference Fourier ◽  
Ideal Method

Although difference Fourier techniques are standard in X-ray crystallography it has only been very recently that electron crystallographers have been able to take advantage of this method. We have combined a high resolution data set for frozen glucose embedded Purple Membrane (PM) with a data set collected from PM prepared in the frozen hydrated state in order to visualize any differences in structure due to the different methods of preparation. The increased contrast between protein-ice versus protein-glucose may prove to be an advantage of the frozen hydrated technique for visualizing those parts of bacteriorhodopsin that are embedded in glucose. In addition, surface groups of the protein may be disordered in glucose and ordered in the frozen state. The sensitivity of the difference Fourier technique to small changes in structure provides an ideal method for testing this hypothesis.

3-D reconstruction of molecular shape from microcrystal thin sections

1983 ◽  
Vol 41 ◽  
pp. 748-749
Author(s):  
S. Cusack ◽  
J.-C. Jésior
Keyword(s):  
Three Dimensional ◽  
Molecular Shape ◽  
Biological Molecules ◽  
Fourier Space ◽  
Single Particles ◽  
Thin Sections ◽  
Standard Methods ◽  
X Ray ◽  
X Ray Crystallography ◽  
Dimensional Reconstruction

Three-dimensional reconstruction techniques using electron microscopy have been principally developed for application to 2-D arrays (i.e. monolayers) of biological molecules and symmetrical single particles (e.g. helical viruses). However many biological molecules that crystallise form multilayered microcrystals which are unsuitable for study by either the standard methods of 3-D reconstruction or, because of their size, by X-ray crystallography. The grid sectioning technique enables a number of different projections of such microcrystals to be obtained in well defined directions (e.g. parallel to crystal axes) and poses the problem of how best these projections can be used to reconstruct the packing and shape of the molecules forming the microcrystal.Given sufficient projections there may be enough information to do a crystallographic reconstruction in Fourier space. We however have considered the situation where only a limited number of projections are available, as for example in the case of catalase platelets where three orthogonal and two diagonal projections have been obtained (Fig. 1).

Electron microscopy of rabbit FC crystals

1983 ◽  
Vol 41 ◽  
pp. 730-731
Author(s):  
Robert A. Grant ◽  
Laura L. Degn ◽  
Wah Chiu ◽  
John Robinson
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
High Resolution Electron Microscopy ◽  
Molecular Replacement ◽  
X Ray ◽  
X Ray Crystallography ◽  
Resolution Electron ◽  
Replacement Technique ◽  
Hydrated Crystal ◽  
Molecular Structure Analysis

Proteolytic digestion of the immunoglobulin IgG with papain cleaves the molecule into an antigen binding fragment, Fab, and a compliment binding fragment, Fc. Structures of intact immunoglobulin, Fab and Fc from various sources have been solved by X-ray crystallography. Rabbit Fc can be crystallized as thin platelets suitable for high resolution electron microscopy. The structure of rabbit Fc can be expected to be similar to the known structure of human Fc, making it an ideal specimen for comparing the X-ray and electron crystallographic techniques and for the application of the molecular replacement technique to electron crystallography. Thin protein crystals embedded in ice diffract to high resolution. A low resolution image of a frozen, hydrated crystal can be expected to have a better contrast than a glucose embedded crystal due to the larger density difference between protein and ice compared to protein and glucose. For these reasons we are using an ice embedding technique to prepare the rabbit Fc crystals for molecular structure analysis by electron microscopy.

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