Isolation and biological evaluation of chromone alkaloid dysoline,a new regioisomer of rohitukine from Dysoxylum binectariferum

The chromone alkaloid dysoline (1), a new regioisomer of rohitukine (2) along with rohitukine and rohitukine-N-oxide (3) were isolated from the stem barks of Dysoxylum binectariferum. The structure of dysoline (1) was determined by extensive 2D-NMR studies and the absolute configuration was established by NOESY and CD spectra. Dysoline (1) consisted of a 5,7-dihydroxy-2-methylchromone nucleus substituted with a 2′-hydroxylated N-Me piperidine ring at the C-6 position. Dysoline differs from rohitukine by the position of the piperidine ring on the chromone nucleus. Dysoline displayed promising cytotoxicity in HT1080 fibrosarcoma cells with an IC₅₀ of 0.21 μM, and also displayed significant inhibition of proinflammatory cytokines TNF-α and IL-6.     

Synthesis of Aristotelia-Type Alkaloids. Part III. (3R,4R)- and (3R,4S)-1-p-menthene-3,8-diol and the corresponding racemates: Preparation and assignment of configuration

A 1:1 mixture of the racemic trans- and cis-1-p-menthene-3,8-diols ((±)- 3 and (±)- 4 , resp.) was readily prepared in 3 steps starting from 3-methyl-2-cyclohexen-1-one. The relative configuration of the diols, purified via the corresponding cyclocarbonates, was assigned by ¹H-NMR spectroscopy and found to be at variance with tentative claims in the literature. Optically active samples of 3 and 4 were prepared by resolution of the racemates with (R)-1-phenylethylamine. The absolute configuration of the resulting diols was determined by chemical correlation with standards of known absolute configuration.     

Rogioldiol A,a new obtusane diterpene,and rogiolal,a degraded derivative,of the red seaweed Laurencia microcladia from II rogiolo along the coast of tuscany: A Synergism in Structural Elucidation

The structure of rogioldiol A ((?)- 1 ), isolated from the red seaweed Laurencia microcladia, was determined. Employing the exciton-coupling technique for rogioldiol A p-bromobenzoate ( 2 ), the absolute configuration at C(9) of (?)- 1 was assigned, and, together with extensive NMR experiments, the absolute configuration at C(10) and preferred conformations of (?)- 1 were determined. The absolute configuration of the hetero-substituted cyclohexane ring was deduced in analogy from the X-ray structure of 4 , a derivative of the aldehyde 3 , which was isolated from the same seaweed and is believed to be a degradation product of (?)- 1 .     

Cyclobutanones through SNi' ring closure, a mechanistic study

Mechanistic studies on the intramolecular nucleophilic substitution with allylic rearrangement (SNi' reaction) and a new stereoselective access to substituted cyclobutanones are reported. 4,4-Dialkyl-5-oxohex-2E-en-1-yl methanesulfonates 4 were converted to 2,2-dialkyl-3-vinylcyclobutanones 6 by SNi' ring closure. The stereochemical analysis of the reaction was achieved through ring closure of (6S)-6-chloro-3,3-diethylhept-4E-en-2-one (S)-17, defined by the absolute configuration of C(6), leading to (3S)-2,2-diethyl-3-(prop-1E-en-1-yl)cyclobutanone (S)-(E)-18 and (3R)-2,2-diethyl-3-(prop-1Z-en-1-yl)cyclobutanone (R)-(Z)-18, in a ratio of 85:15, with almost complete transfer of chirality (>97%). The absolute configuration of (S)-17 was determined by X-ray diffraction analysis of the camphanoate derivative 16. The absolute configuration of the cyclobutanone products (S)-(E)-18 and (R)-(Z)-18 was determined by Raman optical activity spectroscopy. Comparison of the absolute configuration of (S)-17 and the resulting (E)- and (Z)-cyclobutanones 18 allowed the conclusion that the SNi' reaction proceeds with syn geometry relative to the leaving group.     

Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus

Aflastatin A (1) is a specific inhibitor of aflatoxin production by Aspergillus parasiticus. It has the novel structure of a tetramic acid derivative with a long alkyl side chain. The absolute configurations of 29 chiral centers contained in 1 were chemically elucidated in this study. First, four small fragment molecules were prepared from 1 or its methyl ether (2), and their absolute structures were assigned as N-methyl-D-alanine, (2S,4R)-2, 4-dimethyl-1,6-hexanediol dibenzoate, (R)-3-hydroxydodecanoic acid, and (R)-1,2,4-butanetriol tribenzoate. Next, an acyclic fragment molecule 3 with 13 chiral centers was obtained from 1 by NaIO(4) oxidation, and its relative stereochemistry was elucidated by J-based configuration analysis. By analyzing coupling constants of (3)J(H,H) and (2,3)J(C,H) and ROE data, the relative configuration of 3 was verified. Finally, by further J-based configuration analysis using a fragment molecule 7 prepared from 2 with 28 chiral carbons, all relative configurations in the alkyl side chain of 1 were clarified. By connecting these relative configurations with the absolute configurations of first four fragment molecules, the absolute stereochemistry of 1 was fully determined.     

Reinvestigation of absolute stereostructure of (-)-rosiridol: structures of monoterpene glycosides, rosiridin, rosiridosides A, B, and C, from Rhodiola sachalinensis

Three new (-)-rosiridol glycosides, rosiridosides A, B, and C, were isolated from the roots of Rhodiola sachalinensis together with rosiridin [(-)-rosiridol 1-O-beta-D-glucopyranoside]. In the course of the structure elucidation of those new glycosides, the absolute configuration of the 4-position in (-)-rosiridol was reinvestigated. On the basis of the application of the modified Mosher's method for (-)- and (+)-rosiridol derivatives, the absolute configuration of the 4-position in (-)-rosiridol should be revised to be S orientation from the recently assigned R form, so that the absolute stereostructures of rosiridosides A, B, and C and rosiridin were determined.     

An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331 and the reassessment of the absolute configuration

GT-2331 is a potent histamine H(3) antagonist which has entered clinical trials. Efficient multigram syntheses of this compound and its enantiomer are described. The literature reports that GT-2331 is the dextrorotatory (+), more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole with the absolute configuration of (1R,2R)-1. However, we found that the dextrorotatory, more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole has the (1S,2S) absolute configuration. We suggest a reconsideration of the absolute configuration of GT-2331.     

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.     

Synthesis of optically active forms of a-factor the inducer of streptomycin biosynthesis in inactive mutants of streptomyces griseus

The absolute configuration at C-3 of A-factor, 2-(6-methylheptanoyl)-3-hydroxymethyl - 4 - butanolide 1a, was determined to be S by synthesizing both enantiomers of it from paraconic acid. (3S)-A-factor was 2.5 times more active than the (3R)-isomer as the inducer of streptomycin biosynthesis in inactive mutants of Streptomyces griseus.     

Total synthesis of malyngamides K, L, and 5'-epi-C and absolute configuration of malyngamide L

An accelerated, enantioselective, and general synthetic route to a class of malyngamides, K (1), L (3), and 5'-epi-C (4), bearing a cyclohexenone ring or a heavily oxygenated six-membered ring and a vinyl chloride structural motif was developed. The key step was the Suzuki cross-coupling reaction of boronic acids 6-8 with unsaturated carboxylic amides 5a,b possessing the chlorovinyl iodide functionality for the construction of the skeletons of 1-4. The key intermediates 10a,b were prepared using Ogilvie's method for the construction of the chlorovinyl iodide functionality. The NMR data of the synthetic compound 2 were in full agreement with those of the reported product, and the discrepancy in the specific rotation data suggested that the correct structure of malyngamide L should be 3, in which the absolute configuration of the amine part was enantiomeric to that in compound 2. Then the absolute configuration of the stereogenic center at C(3') and C(4') in malyngamide L was confirmed by synthesis of compound 3.     

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.     

The absolute configuration of (+)-(E)-4-phenylbut-3-ene-2-ol

A derivative of (+)-(E)-4-phenylbut-3-ene-2-ol is shown by X-ray crystallography to be of (R) configuration, confirming the assumption in the literature that the absolute configuration of (+)-(E)-4-phenylbut-3-ene-2-ol is (R).     

Isolation and absolute configuration determination of aliphatic sulfates as the Daphnia kairomones inducing morphological defense of a phytoplankton-part 2

4,8-Dimethylnonyl sulfate (1) and 3-methyl-4E-decenyl sulfate (2) were isolated from Daphnia pulex as the Daphnia kairomones that induced morphological defense of a freshwater phytoplankton Scenedesmus gutwinskii var. heterospina (NIES-802). The absolute configuration at C4 of 1 was determined by Ohrui's method applied to alcohol 3. The absolute stereochemistry at C3 of 2 was determined by (1)H-NMR analysis of the (R)-1NMA ester of alcohol 11.     

Absolute Conformation and Configuration of (2S, 3S)-3-Acetoxy-5-(dimethylaminoethyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one Chloride (Dilthiazem Hydrochloride)

Resolution of racemic cis-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid ( 2 ) via the cinchonidine salt 3 , and brucine salt 4 , isolation of the calcium salts (+)- and (?)- 5 , as well as their cyclization to enantiomeric 1,5-benzothiazepines (+)- and (?)- 1 , are described. X-Ray single-crystal analysis reveals (2S, 3S) absolute configuration of (+)- 1 on the basis of tentative comparison of CD data with those for the 1,4-benzodiazepine derivative (+)- 8 of known absolute configuration.     

Synthesis and absolute configurations of the cytotoxic polyacetylenes isolated from the callus of Panax ginseng

Panaxacol (1) and dihydropanaxacol (2), cytotoxic polyacetylenes isolated from the callus of Panax ginseng, were synthesized starting from D-(-)-diethyl tartrate. The absolute configuration of 1 was determined to be 9R, 10R and the absolute configuration at C-3 of 2 was tentatively assigned as 3S by the application of the R(+)-alpha-methoxy-alpha-(trifluoro methyl)phenylacetyl (MTPA) method.     

Determination of molecular stereochemistry using vibrational circular dichroism spectroscopy: absolute configuration and solution conformation of 5-formyl-cis,cis-1,3,5-trimethyl-3-hydroxymethylcyclohexane-1-carboxylic acid lactone

The determination of the absolute configuration of chiral molecules is an important aspect of molecular stereochemistry. Vibrational circular dichroism (VCD) is the extension of electronic CD into the infrared region where fundamental vibrational transitions occur. VCD has a number of advantages over all previous methods of absolute configuration assignment. The absolute configuration and predominant solution-state conformation in CDCl(3) of the chiral lactone, 5-formyl-cis,cis-1,3,5-trimethyl-3-hydroxymethylcyclohexane-1-carboxylic acid lactone, 1, obtained by the comparison of measured and calculated VCD spectra, are reported. It is found that (-)-1 corresponds to the absolute configuration (1S,3S,5R)-1.     

Stereochemistry of amino-carbonyl compounds—VII: Absolute and ralative configuration of some diastereomeric 1,3-amino-alcohols.

The absolute configuration of (+)-4-dimethylamino-2,4-diphenyl-butan-2-ol and (+)-4-piperidino-2-phenyl-pentan-2-ol, the predominant diastereomers obtained by reaction of (+)-3-dimethylamino-1,3-diphenyl-propan-1-one with MeLi and (+)-3-piperidino-1-phenyl-butan-1-one with MeMgI, respectively, was determined by chemical correlation. The relative configurations of the diastereomers afforded by such reactions were thus assigned.     

Derivatives of vibralactone from cultures of the basidiomycete Boreostereum vibrans

Four new natural products possessing vibralactone skeleton, 1,5-secovibralactone (1), vibralactone B (2), vibralactone C (3) and acetylated vibralactone (4), together with known compound vibralactone (5), had been isolated from cultures of the basidiomycete Boreostereum vibrans. The structures of 1-4 were elucidated on the basis of spectroscopic methods. The absolute configuration of 1 was suggested to be S by computational methods.     

Synthesis and absolute configuration of A-factor,the inducer of streptomycin biosynthesis in inactive mutants of Streptomyces griseus

The absolute configuration at C-3 of A-factor, 2-(6-methylheptanoyl)-3-hydroxymethyl-4-butanolide $\text{1a}$, was determined to be $\text{S}$ by synthesizing(3$\text{S}$)-(+)-A-factor.     

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.