Synthesis of (−)-okundoperoxide and determination of the absolute configuration of natural (+)-okundoperoxide

The first enantioselective synthesis of (3S,4aR,8aR)-1 (the enantiomer of natural okundoperoxide) has been accomplished. The synthesis features: 1) stereoselective installation of the peroxy functionality (16 → 17); 2) ring opening of peroxyacetal and subsequent intramolecular reaction between the hydroperoxide and the vinyl epoxide to form the peroxy six-membered ring (5 → 1). The absolute configuration of okundoperoxide was determined to be 3R,4aS,8aS by comparing specific rotations of the synthetic sample and the natural product.     

Extraction and determination of biologically active components of St. John’s wort and its pharmaceutical preparations

A procedure is developed for the determination of biologically active substances (BAS) of common St. John’s wort (Hypericum perforatum L.) by HPLC using two columns, Luna C18, 100 Å (for the determination of phenolcarboxylic acids and flavonoids), and Onyx Monolithic C18 (for the determination of phloroglucinols and naphthodianthrones), in the gradient elution mode with diode array detection. The detection limits for analytes are 0.05–0.20 μg/mL. To optimize the conditions, we studied the extraction of biologically active substances from St. John’s wort by a water–ethanol solution at different temperatures and pressures and under the effect of microwave radiation and ultrasound. The maximum amounts of substances were extracted in a dynamic mode under heat and pressure. The procedure was applied to the St. John’s wort samples of different brands and some pharmaceutical products based on it. The components of extracts were identified by retention times, UV spectra, and mass spectra. It was shown that the content of biologically active substances in pharmaceutical samples of St. John’s wort depends on the herb habitat. It was shown that hyperforin decomposed in pharmaceutical formulations based on St. John’s wort during storage.     

Assessment of the absolute configuration of a series of (3R)-3-hydroxy-3-alkyl-β-lactams

The absolute stereochemistry of a series of (3R)-3-hydroxy-3-alkyl-β-lactams has been determined by circular dichroism and NMR spectroscopies. The sign of the circular dichroism band between 250 and 220 nm was related to the stereochemistry by applying the β-lactam sector rule. The NMR analysis unambiguously determines the relative configuration at C3 and C4 of the β-lactam ring. The reliability of the method has been proved by X-ray analysis of two of the examined compounds. The obtained results are in agreement with the mechanism proposed for the employed synthetic route.     

Resolution and determination of the absolute configuration of 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde

Racemic 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde 1 was resolved via the formation of diastereomeric dioxolanes with (S)-(+)-1-phenyl-1,2-ethanediol. Four stereoisomers were separated by column chromatography. The absolute configuration of one of them (2′′R, 4′′S,1R) was established by X-ray diffraction. Acid hydrolysis of the dioxolanes afforded quantitatively (R)- and (S)-enantiomers of 1. Optical rotatory dispersion (ORD) spectra of both enantiomers are also reported.     

Ab initio simulation of the sum-frequency generation response of optically active liquids in the presence of a dc electric field —determination of the absolute molecular configuration

Quantum chemical computations have been performed to evaluate the first and second hyperpolarizability quantities of the interference term, linear in the external static electric field, that appear in the electric field-induced sum-frequency generation signal of chiral liquids. These are performed at the time-dependent Hartree-Fock level on the prototypical 1,1′-bi-2-naphtol chiral species.     

Resolution and determination of the absolute configuration of 3,3′4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid

(±)-3,3′4,4′-Tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid 1 was resolved via diastereomeric salts with brucine. The (R)-absolute configuration of (+)-1 was determined by X-ray crystallography.     

Synthesis, resolution, and absolute configuration of difunctionalized Tröger's base derivatives

Two racemic derivatives of Tr?ger's base, the 2,8-diboronic acid ester 6 and the 3,9-dibromo-substituted derivative 5, were synthesized and successfully resolved by HPLC on a chiral stationary Whelk-01 phase on a semipreparative scale, thereby giving rise to both enantiomers in a pure form. These functionalized C(2)-symmetric building blocks are valuable precursors for a variety of further applications. Their absolute configurations were determined by comparison of their quantum chemically calculated CD and UV/Vis spectra with the experimental ones and were independently confirmed by X-ray diffraction analysis.     

Synthesis of ( ) 8-O-Cinnamyl-p-chlorogoniotriol and its Analogues

HowiinolAI',anovellactoneisolatedfromtheethanolicextractsoftherootandsternbarkofGoniolhanlush()TI)iiMerr.(Annoaceae)inourlaboratory.hasbeenshowntopossesssignificantantitullloractivitiestowardhumantumor117vilroandI,71'if'oandfoxytoxlcit}.Recently.wehavesynthesized1anditsderivativeswitllditTerentestergroupsstartingfromcommerciallyavailablea-D-glucoheptonic-y-lactone.Inordertotindtheirrelationshipofstructureandactivityandtosearchfordrugswithmorepotentantitumoractivity.wehavesynthesized( )8-O-…     

7-β- and 10-β-Hydroxylated congeners of CAF-603; elucidation of absolute configuration of CAF-603 family,and their SAR studies in the anti-fungal activity

Novel 7-β- and 10-β-hydroxylated congeners of CAF-603 (4 and 5, respectively) were isolated from Trichoderma crassum. Relative configuration of 4 was determined by NOE experiments. Stereochemistry of 7-β-hydroxy group in 5 was established by a combination of vicinal ³J_H–H analyses and quantum chemical calculations. Absolute configurations of 4 and 5 were established by observing the Cotton effects of their bis(2-naphthoate) esters. T. crassum also produce known CAF-603 (1), 14-hydroxy and 8,9-β-epoxy derivatives (2 and 3, respectively). Present study first established the absolute configuration of CAF-603 family by taking their biosyntheses into account. Preliminary biological experiments revealed that the molecular target strictly recognizes the β-side of the cycloheptane ring.     

Synthesis of ( )-5α-Hydroxy-β-selinene and (-)-5β-Hydroxy-β-selinene

Eudesmanederivativeshavebeendrawingconsiderableattentionduetotheirwidespectrumofbiologicalproperties,particularlyantifeedant,cellgroWthinhibitoryandplantgroWthregulatingactivitiesl'2.Recently,twoepimericeudesmanederivatives( )-5a-hydroxy-6-selinene1and(-)-56-hydroxy-6-selinene2wereisolated3fromtheaerialpartsofCSubtraPicaFMell.,andtheirstructuresweredeterminedbyspectroscopicmethods.Herein,wereportafacilesynthesisofbothtwodiastereomers1and2from( )-dihydrocarvone3infivesteps,usingtheregioselect…     

Reassignment of the absolute configuration of the baker's yeast reduction of (±)-ethyl 1-allyl-2-oxocyclopentanecarboxylate

The baker's yeast reduction of (±)-ethyl 1-allyl-2-oxocyclopentanecarboxylate under aqueous conditions in the presence of CuO yields (1S,2S)-(+)-ethyl 1-allyl-2-hydroxycyclopentanecarboxylate and the unreacted enantiomer (1R)-(−)-ethyl 1-allyl-2-oxocyclopentanecarboxylate. The absolute configuration of the secondary alcohol was determined from the X-ray crystal structure of the (1S)-10-camphorsulfonyl derivative of (1S,2S)-(+)-ethyl 1-allyl-2-hydroxycyclopentanecarboxylate. This refutes configurational claims based on CD/ORD and chemical affiliation techniques currently reported in the literature for this reaction.     

9-(β-pyridylmethylene)-4-azafluorene synthesis of the Z- and E-isomers of its methiodides and reduction of the Z-isomer

The 9-(-pyridylmethylene)-4-azafluorene was obtained as the mixture of the Z- and E-isomers. Condensation of 4-azafluorene with methiodides of 3-formylpyridine afforded the methiodides of these isomers which were isolated in discrete form. Their configuration was established. It was established using the example of the reduction of the methiodide of the Z-isomer by sodium borohydride that the -pyridinium portion of this quaternary salt is completely reduced to the piperidyl.Russian University of the Friendship of Peoples, Moscow 117923. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1243–1246, September, 1998.     

Synthesis of optically active α-(allenyl)- and α-substituted-α-(allenyl)glycines

The synthesis of various types of optically active α-(allenylsilane-containing)glycines via a chirality-transferring ester-enolate Claisen rearrangement of α-acyloxy-α-alkynylsilanes is described. The conversion of the rearranged products into the optically active silicon-free α-(allenyl)- and α-substituted-α-(allenyl)glycines was achieved by the removal of the Me₂PhSi- or TMS group from the allene terminus.     

Enantioselective synthesis of natural biologically active ivaide A: 1,3-di-(R)-β-hydroxy-glyceride glycerol

The natural 1,3-di-β-hydroxy-glyceride glycerol ivaide A 1 from Ajuga iva has been synthesised by diacylation of dihydroxyacetone with 3-hydroxyhexadecanoic acid, followed by reduction to the corresponding glycerol derivative. The enantiomerically pure (R)-β-hydroxyhexadecanoic ester intermediate 6 was obtained by a coupling reaction of an ethylacetoacetate dianion and the corresponding bromoalkyl, followed by the known reduction of the resulting β-ketoester 5 by fermenting baker's yeast.     

SYnthesis and absolute configuration of (−)-pentalenolactone E methyl ester

The naturally occurring enantiomer of pentalenolactone E was synthesized as its levorotatory Me ester1 starting from (+)-2-ethoxycarbonyl-7,7-ethylenedioxybicyclo[3.3.0]octan-3-one3, which was obtained by treating (±)-3 with baker's yeast. The absolute configuration of pentalenolactone E Me ester was established as depicted in1.     

The absolute configuration of (+)- and (−)-1-phenylundec-4-yn-3-ols. Synthesis of (R)-4-dodecanolide,a component of the defensive secretion of rove beetle Bledius mandibullaris

Hydrogenation of the triple bond of (+)-1-phenylundec-4-yn-3-ol (obtained from (+)-[η⁶-(3-hydroxyundec-4-yn-1-yl)benzene]chromium tricarbonyl) with the NaBH₄-NiCl₂·6H₂O reagent system in MeOH leads to (?)-1-phenylundecan-3-ol. Ozonolysis of the phenyl ring in the corresponding acetate gives (R)-(?)-acetoxydodecanoic acid, lactonization of which leads to the known (R)-(+)-4-dodecanolide. The starting (+)-1-phenylundec-4-yn-3-ol was thus shown to have the S-configuration.     

Synthesis of (S)-(−)-β-cuparenone and (S)-(−)-cuparene

A short and efficient synthesis of the title compounds is described. (S)-(−)-β-Cuparenone was prepared in 31% yield from p-tolualdehyde and mesityl oxide in eight steps. Absolute stereochemistry was established by means of a diastereoselective cyclopropanation using (R,R)-hydrobenzoin as a recoverable auxiliary.     

Synthesis and electron transfer studies of redox active trans-β-diketonate Ni(II) complexes

The synthesis of trans-[Ni(dbm)₂(RN=C(Me)NHR)₂] (dbm?=?1,3-diphenylpropanedionate; R?=?phenyl, p-tolyl, 3,5-dimethylphenyl, 3,5-dichlorophenyl) has been achieved by reaction of [Ni(dbm)₂(H₂O)₂] with two equivalents of the amidine ligands, RN=C(Me)NHR. X-ray crystallographic studies reveal that trans-[Ni(dbm)₂(RN=C(Me)NHR)₂] (R?=?3,5-dimethylphenyl) exhibits an intramolecular N?CH···O hydrogen bond, which along with the large steric bulk of the amidine ligands may enforce the trans geometry. Electrochemical studies show a strong dependence of the oxidation potential on the substituent groups despite their remote position. DFT calculations indicate that the HOMO consists of Ni-ligand ??* orbitals with a significant contribution from the amidine ligands.     

Synthesis and Cyclization of N-(4-Phenoxyphenyl)-β-alanines

We have used the reaction of 4-aminodiphenyl ester with acrylic, methacrylic, crotonic, and itaconic acids to synthesize N-substituted -alanines, which undergo ring closure to form derivatives of dihydropyrimidinedione and 4-carboxy-2-pyrrolidinone. We have studied the reactions of acylation and recyclization of the dihydropyrimidinedione ring, and we have synthesized derivatives of 4-carboxy-1-(4-phenoxyphenyl)-2-pyrrolidinone: arylidene hydrazides, 2[(2-oxo-4-pyrrolidinyl-1-(4-phenoxyphenyl)]benzimidazole.