Lipase-catalyzed resolution of 5-acetoxy-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene. Application to the synthesis of (+)-(3R,4S)-cis-4-hydroxy-6-deoxyscytalone, a metabolite isolated from Colletotrichum acutatum

(+)-cis-4-Hydroxy-6-deoxyscytalone, a natural product bio-synthesized by Colletotrichum sp., has been prepared and its absolute configuration confirmed as 3R,4S, the key step being a kinetic racemic resolution of a cis-diol easily obtained from commercial 1,2,3,4-tetrahydronaphthalen-1,5-diol. Four lipases and different reaction conditions were tested in order to obtain the best yield and enantiomeric excess. Confirmation of absolute configuration was made by NMR using a single-derivatization low-temperature procedure and MPA as the auxiliary reagent.     

5-Methyl-4H-1,3-dioxins,new chiral building blocks: transformation into (R)- and (S)-4-hydroxymethyl-4-methyl-1,3-dioxolanes via oxidation and rearrangement and determination of the absolute configuration

5-Methyl-4H-1,3-dioxins obtained by asymmetric double-bond isomerization have been transformed into 4-hydroxymethyl-4-methyl-1,3-dioxolanes by m-chloroperbenzoic acid oxidation, ring contraction and reduction. The stereochemical course of this transformation has been studied, while the relative configuration of the intermediate oxidation product and the absolute configuration of the resulting camphanyl ester of 2-tert-butyl-4-hydroxymethyl-4-methyl-1,3-dioxolane was established by X-ray crystallography. From these results, the absolute configuration of the dioxins has been deduced.     

epi-Aszonalenins A, B, and C from Aspergillus novofumigatus

Three new benzodiazepines have been isolated from an unusual chemotype of Aspergillus novofumigatus: epi-aszonalenins A, B, and C. The structures were elucidated by use of one- and two-dimensional NMR spectroscopic techniques and HR ESI MS. The relative configuration was established on the basis of a single crystal X-ray diffraction study of epi-aszonalenin A and the absolute configuration was determined by optical rotation comparison with the literature data. The absolute configurations of epi-aszonalenins B and C were determined by circular dichroism comparison to epi-aszonalenin A.     

Absolute configuration reassignment of two chromanes from Peperomia obtusifolia (Piperaceae) using VCD and DFT calculations

Previous analysis of the ECD spectra of two prenylated benzopyrans isolated from Peperomia obtusifolia, by means of the helicity rule for the chromane chromophore, resulted in the incorrect assignment of their absolute configuration, (S) instead of (R) for a deduced P-helicity of the chromane ring for the (+)-enantiomers. This was discovered by the application of DFT calculations and VCD spectroscopy. Experimental and calculated (B3LYP/6-31G(d)) VCD and IR spectra were compared, and a definitive absolute configuration of (+)-1 and (+)-2 is reassigned directly in solution as (R). The assumption of equatorial positioning of bulky groups, shown here to be invalid for the title molecules, is the underlying cause of the previous incorrect assignment of absolute configuration. Moreover, TDDFT (B3LYP/6-311++G(2d,2p)//B3LYP/6-31G(d)) calculations of ECD spectra have shown that both P- and M-helicity of the heterocyclic ring, for a given absolute configuration, lead to the same sign for the ¹L_b ECD band, thus bringing into question the validity of the empirical ECD helicity rule for chromane molecules.     

Isolation and structure elucidation of (−)-idescarparide,a new spiro compound from Idesia polycarpa

(−)-Idescarparide, a new spiro compound possessing a tetrahydrobenzodioxole structure from the fruit of Idesia polycarpa Maxim. was identified to be a dimer of (−)-idescarpin by spectroscopic analysis. The absolute configuration of (−)-idescarpin was firstly determined to be of S form by using single-crystal X-ray diffraction. The absolute configuration of (−)-idescarparide was confirmed by comparison with semi-synthetic (−)-idescarparide, achieved via triethylamine-catalyzed dimerization of (−)-idescarpin. (−)-Idescarparide significantly reduced lipid production in 3T3-L1 cells.     

The absolute configuration of angular 3′-acyloxypyranocoumarins by vibrational circular dichroism exciton chirality

A complex mixture of lomatin C-3′ esters and (−)-O-angeloyllomatin 1 was isolated from the seeds of Prionosciadium thapsoides. Since a literature search revealed that some lomatin C-3′ monoesters have positive specific rotations, while others had negative values, the absolute configuration of all of the molecules was determined to be (R) by exciton chirality in the infrared region, and by chemical correlation. A single crystal X-ray study of acetyllomatin 3, using the Flack and Hooft parameters, independently confirmed this absolute configuration.     

Absolute configuration of the four stereoisomers of valnoctamide (2-ethyl-3-methyl valeramide), a potentially new stereospecific antiepileptic and CNS drug

Valnoctamide (2-ethyl-3-methyl valeramide, Nirvanil^®, VCD), a mild tranquilizer endowed with anticonvulsant properties, exhibits diastereoselective and enantioselective pharmacokinetics in healthy subjects and epileptic patients. The purpose of this paper is to assign the absolute configuration of the four VCD stereoisomers and to describe the stereoselective synthesis used to prepare two-key VCD stereoisomers. We have synthesized two out of the four stereoisomers, with high diastereomeric excess, by two different synthetic methods. In both methods the (S) configuration at C-3 of VCD was fixed by synthesizing (S)-3-methyl valeric acid from l-isoleucine. In the first method the diastereomeric mixture (2RS,3S)-VCD was prepared. This mixture gave one of the diastereomers via repeated crystallizations, and its absolute configuration (2R,3S)-VCD, was established by X-ray crystallography using a single crystal. The absolute configuration of all four VCD stereoisomers, separated by chiral gas chromatography, was established on the basis of diastereomeric and enantiomeric correlations. In order to assess stereoselective pharmacodynamic properties of VCD, the single stereoisomers have to be synthesized. Stereoselective synthesis of (2R,3S)-VCD and (2S,3S)-VCD was accomplished by using chiral oxazolidinone auxiliaries. These diastereomers were obtained in 99.6% diastereomeric excess.     

A convenient method for the assignment of the absolute configuration to cyclic amines

We have assigned the absolute configuration to trans-2,5-dimethylpyrrolidine and trans-2,6-dimethyl-piperidine through radical chlorination in ω-1 position of optically active amines, 2 and 5, of known absolute configuration, followed by cyclization. CD curves of 1f and 4g derivatives indicate that the reaction is stereospecific. The absolute configuration of trans-2,5-dimethyl-Δ³-pyrròline has also been determined.     

Total synthesis of diaportheone A

Diaportheone A (1), a chromone natural product was previously isolated from the endophytic fungi Diaporthe sp. P 133. Its structure was established by spectroscopic methods, however, its absolute configuration remained undefined. This study dealt on the total synthesis of diaportheone A (1) utilizing the cyclization and in situ thermal syn-elimination of a β-ketosulfoxide. The C-1R absolute configuration of the natural product was established by X-ray crystallography of the synthetic diaportheone A (1) (>99%?ee) and comparison with the optical rotation.     

Synthesis to determine the absolute configuration of (−)-pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea

The absolute configuration of (−)-pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea, was determined to be R by synthetic studies.     

1,3-Dipolar addition of nitrones to symmetrically substituted allenes: for the determination of absolute configuration of chiral allenes by NMR spectroscopy

5-Methyl-5-phenylpyrroline N-oxide was proved to be a useful 1,3-dipole for determining the absolute configuration of chiral allenes by means of NMR spectroscopy.     

Application of the cd homoallylic benzoate method as a chiroptical tool for determination of absolute configuration

After the conformation I was clarified to 5α-,10α,-cis-solidagolactones by ¹H NMR measurement with Eu(dpm)₃ and chemical transformations, the CD homoallylic benzoate chirality method was applied to the homoallylic alcohol system of solidagolactone IV ($\text{1a}$) for a chiroptical determination of the absolute configuration. The result agreed with absolute configuration elucidated by x-ray analysis, indicating the usefulness of the cd method.     

c-4-Amino-t-3-hydroxy-r-1-cyclohexanecarboxylic acid and cis-4-amino-3-oxo-1-cyclohexanecarboxylic acid—mimetics of dipeptides with a twisted cis-amide bond

The stereoselective synthesis of the title compounds has been performed. The relative configuration of methyl c-4-(tert-butoxycarbonylamino)-t-3-hydroxy-r-1-cyclohexanecarboxylate was confirmed by X-ray diffraction methods and its conformation in solution analyzed by NMR. The peptides containing this compound were synthesized and resolved into pure diastereoisomeric forms. Their absolute configuration was determined by independent stereospecific synthesis.     

Deracemisation of aromatic β-hydroxy esters using immobilised whole cells of Candida parapsilosis ATCC 7330 and determination of absolute configuration by 1H NMR

Deracemisation of aryl and substituted aryl β-hydroxy esters using immobilised whole cells of Candida parapsilosis ATCC 7330 yields the corresponding (S)-enantiomer in >99% enantiomeric excess and good yield (up to 68%). The absolute configuration of ethyl 3-(2,4-dichlorophenyl)-3-hydroxy propanoate and ethyl 3-hydroxy-5-phenyl-pent-4-enoate as determined by ¹H NMR using MTPA chloride was found to be ‘S’. The chemical shifts of the methoxy groups of the two diastereomeric MTPA esters were used as diagnostic signals to determine the absolute configuration.     

Determination of the absolute stereochemistry of Etzionin

The absolute configuration of Etzionin, a marine peptide-like compound isolated in 1989 from a red tunicate collected from the Red Sea has been determined by a combination of synthetic and spectroscopic procedures. Finally, its absolute stereochemistry has been established as 3S,3′R.     

The absolute configuration of simple aliphatic alcohols through a chemical/computational approach: triarylether derivatives of (+)-endo-2-norborneol as a case study

The reliable determination of the absolute configuration of (+)-endo-2-norborneol 1, chosen as a representative case of simple aliphatic UV–vis transparent alcohols, was obtained by transforming this compound in its 1-naphthyl-diphenylmethyl ether 5 whose ECD spectrum displays several, low-lying, intense Cotton effects, which can be satisfactorily simulated in position, sign, and intensity by TDDFT/B3LYP/6-31G¹ calculations. This result represents a possible, general, new approach to the absolute configuration of aliphatic alcohols.     

Asymmetric synthesis and absolute configuration of a planar chiral phosphapalladacycle with a ferrocenyl framework

A monodentate optically active tertiary α-ferrocenylethylphosphine was prepared from the corresponding tertiary α-ferrocenylethylamine; Me₂N group substitution by a tert-Bu₂P group occurs with complete retention of the enantiomeric composition and absolute configuration of the α-carbon stereocentre. The cyclopalladation of this phosphine ligand results in the formation of a phosphapalladacycle bearing the elements of central and planar chirality with a high diastereoselectivity. The enantiomeric composition of the CP-palladacycle was determined by ³¹P{¹H} NMR spectroscopy using (S)-prolinate as a chiral derivatizing agent. The structure and absolute configuration of the phosphapalladacycle were established using NMR spectroscopy and an X-ray diffraction study of its (S)-prolinate derivative.     

Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam,Useful Intermediate for the Synthesis of Bioactive Compounds

During the past several years, the frequency of discovery of new molecular entities based on γ- or δ-lactam scaffolds has increased continuously. Most of them are characterized by the presence of at least one chiral center. Herein, we present the preparation, isolation and the absolute configuration assignment of enantiomeric 2-(4-bromophenyl)-1-isobutyl-6-oxopiperidin-3-carboxylic acid (trans-1). For the preparation of racemic trans-1, the Castagnoli-Cushman reaction was employed. (Semi)-preparative enantioselective HPLC allowed to obtain enantiomerically pure trans-1 whose absolute configuration was assigned by X-ray diffractometry. Compound (+)-(2R,3R)-1 represents a reference compound for the configurational study of structurally related lactams.     

Isolation of an anthrabenzoxocinone 1.264-C from Streptomyces sp. FXJ1.264 and absolute configuration determination of the anthrabenzoxocinones

The anthrabenzoxocinones (ABXs) are hexacyclic aromatic compounds with various bioactivities. Some ABXs with two stereogenic carbon centers have been isolated from different actinomycetes. However, none of them have an absolute configuration assigned, which precludes further studies on the structure–activity relationship and biosynthetic mechanisms of the ABXs. An ABX compound 1.264-C was isolated from Streptomyces sp. FXJ1.264. The absolute configuration of 1.264-C was characterized by X-ray crystallographic, electronic, and experimental circular dichroism (CD) analyses. Based on the reported CD and specific rotation data, the absolute configurations of several other ABXs were also assigned.     

Croissamide,a proline-rich cyclic peptide with an N-prenylated tryptophan from a marine cyanobacterium Symploca sp.

Croissamide, a proline-rich cyclic peptide that contains an N-prenylated tryptophan, was isolated from a marine cyanobacterium Symploca sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on chiral HPLC analyses of acid hydrolysates.