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.     

Synthesis of (4R,5S)-(−)- and (4S,5S)-(+)-L-Factors and Muricatacin from D-Glucose

Abstract

In connection with our projects on the synthesis of biologically active 5-hydroxyalkan-4-olides which have a chiral 2.3-diol unit,¹ we have carried out the synthesis of (4R,5S)-(?)- and (4R,5S)-(+)-L-factors (1).² the proposed autoregulators from Streptomyees griseus, and muricatacin (2),³ a biologically active constituent from the seeds of Annona muricata L. via 2.3-dihydroxy aldehydes derived from D-glucose. Hex-3-enofuranose4 was prepared by the elimination of thetriflate derived from D-glucose.     

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.     

Efficient synthesis of (−)-(R)- and (+)-(S)-rolipram

A novel, efficient and protecting group free enantioselective synthetic approach of (?)-(R)-1 and (+)-(S)-rolipram 2 is described employing the organocatalyzed asymmetric Michael addition, Henry condensation, Wittig olefination and reductive lactamization reactions as key steps.     

Synthesis of (+)- and (−)-Tetrabenazine from the Resolution of α-Dihydrotetrabenazine

Abstract

Tetrabenazine (1) was reduced with NaBH₄ to α-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)- and (?)-α-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (?)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.     

Synthesis of (3R, 4R)-1, 2-Divinylglycol and its Unsymmetrical Derivatives : An Application to the Synthesis of R-(+)-α-Lipoic Acid

ABSTRACT

The synthesis of (3R, 4R)-divinylglycol (1) and some of its unsymmetrical derivatives has been described starting from D-mannitol. I has been converted into R-(+)-α-lipoic acid.     

Non-thiazolidinedione antihyperglycaemic agents. Part 4: Synthesis of (±)-, (R)-(+)- and (S)-(−)-enantiomers of 2-oxy-3-arylpropanoic acids

The synthesis of a new series of potent 2-oxy-3-arylpropanoic acid antihyperglycaemic agents in both racemic and non-racemic form is described. Resolution of racemic acids 1 is accomplished via amide formation with either (S)-2-phenylglycinol or (S)-4-benzyloxazolidin-2-one as complementary resolving agents.     

TiCl3-Mediated Synthesis of 2,3,3-Trisubstituted Indolenines: Total Synthesis of (+)-1,2-Dehydroaspidospermidine, (+)-Condyfoline,and (−)-Tubifoline

2,3,3-Trisubstituted indolenine constitutes an integral part of many biologically important monoterpene indole alkaloids. We report herein an unprecedented access to this skeleton by a TiCl₃-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent. The proof of concept is demonstrated firstly by accomplishing a concise total synthesis of (+)-1,2-dehydroaspidospermidine featuring a late-stage application of this key transformation. A sequence of reduction of nitroarene to nitrosoarene followed by 6π-electron-5-atom electrocyclization and a 1,2-alkyl shift of the resulting nitrone intermediate was proposed to account for the reaction outcome. A subsequent total synthesis of (+)-condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2-alkyl shift. The exclusive formation of (+)-condyfoline indicates that the 1,2-alkyl migration follows a concerted Wagner–Meerwein pathway, rather than a stepwise retro-Mannich/Mannich reaction sequence. Conditions for almost quantitative conversion of (+)-condyfoline to (−)-tubifoline by way of a retro-Mannich/1,3-prototropy/transannular cyclization cascade are also documented.     

Synthesis of (−)-(1′S,4aS,8aR)- and (+)-(1′S,4aR,8aS)-4a-ethyl-1-(1′-phenylethyl)-octahydroquinolin-7-ones

A synthesis of the enamine (−)-(1′S)-5-ethyl-1-(1′-phenylethyl)-1,2,3,4-tetrahydropyridine 4 and its application in a synthesis of (−)-(1′S,4aS,8aR)- and (+)-(1′S,4aR,8aS)-4a-ethyl-1-(1′-phenylethyl)-octahydroquinolin-7-ones 5 and 6 is described. In addition, an X-ray study of 6 is reported. Finally, the preparation of (+)-(4aS,8aR)-4a-ethyl-octahydroquinolin-7-one 7 is described.     

Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids and some derivatives

(2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (−)- and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)-(+)-2-methyl-1,2-butanediol.     

Absolute configuration and anti-hypercholesterolemic activity of (+)- and (−)-4-(2,6-dimethylheptyl)benzoic acids

The biologically inactive (+)-enantiomer of 4-(2,6-dimethylheptyl)benzoic acid was converted into the known (R)-3,7-dimethyloctanol withee≥96% by ozonolysis followed by a two-step reduction of the ozonide. This confirmed theR configuration of the starting acid, theS configuration of its biologically active levorotatory antipode, and the absolute configurations assigned to their synthetic precursors. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1316–1318, July, 2000.     

Conformational and configurational chirality of 1,2-dimethylaminoalkylformylcymantrenes. Molecular structure and absolute configuration of (−)578-1-[α-(N,N-dimethylamino)ethyl]-2-formylcymantrene

The molecular structure and the absolute configuration of (−)₅₇₈-1-[α-(N,N-dimethylamino)ethyl]-2-formylcymantrene have been established by the X-ray method. These data were used for the direct determination of the orientation and stereochemistry of the preferable attack of n-BuLi on metallation of [α-(N,N-dimethylamino)ethyl]cymantrene. CD and UV spectra of (−)-(S)-1-[(R-α-(N,N-dimethylamino)ethyl]-2-formylcymantrene (planar and central chirality) and (−)-(S)-1-N,N-dimethylaminomethyl-2-formylcymantrene, I (only planar chirality) and related compounds have been studied, a change in both the sign and the intensity of Cotton effects is observed between solutions of I and II in aprotic solvents and solutions in 0.1 N HCl and quaternary salts of these compounds. The data obtained indicate that the optical characteristics of aminoaldehydes of cymantrene are determined by the conformation of these molecules but not by their absolute configuration.     

Synthesis and biological activity of the (−)-(2R,3S,4S)-3-azido-4-methoxy-2-(1′S-methoxy-2′-azido)ethyl-thiolane

A stereospecific ring contraction reaction, promoted by NaN₃, was detected starting from a thiepane derivative obtained from d-sorbitol, an inexpensive alcohol sugar. The major polyfunctionalized thiolane derivative obtained was investigated as a potential glycosidase inhibitor.     

Synthesis of (+)-altholactone, (+)-7-epi-altholactone, (−)-etharvensin,and (+)-alumheptolide-A using Pd-catalyzed carbonylation

Syntheses of (+)-altholactone isolated from Goniothalamus giganteus and its C-7 epimer (+)-7-epi-altholactone, (?)-etharvensin and (+)-alumheptolide-A were achieved. The lactone ring of these compounds was constructed using Pd-catalyzed carbonylation.     

Synthesis and ozonization of (+)-4α-(1-trimethylsilyloxyethen-1-yl)-2-carene

(+)-4-(1-Trimethylsilyloxyethen-1-yl)-2-carene was synthesized, and the products of its ozonization were identified.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1984–1987, October, 1995.     

Synthesis of biologically active (-)-dehydroiso-β-lapachone and the determination of its absolute configuration

Synthesis of dehydoriso-β-lapachone (1) in both racemic and enantioenriched forms is achieved starting from reduced naphthoquinone equivalents. As for the synthesis of enantioenriched dehydroiso-β-lapachone, introduction of the asymmetric center was carried out by catalytic asymmetric epoxidation of the unfunctionalized trisubstituted olefin using Shi epoxidation diketal catalyst. The construction of isopropenylfurano-1,2-(β)-naphthoquinone was carried out by acidic ring-opening reaction of the epoxynaphthalene and the following diammonium cerium(IV) nitrate (CAN) oxidation. The absolute configuration of naturally occurring (-)-dehydroiso-β-lapachone was finally determined as (R) by comparing the measured optical rotation value of the synthetic (R)-dehydroiso-β-lapachone.     

Stereoselective Synthesis and Characterization of (Z)-(−)-4-(1′-Alkoxyl-1′-alkyloxycarbonyl-methylidene)-5(R)-[(1R)-menthyloxy]-γ-butyrolactones

Abstract

A series of enantiomerically pure (Z)-(?)-4-(1′-alkyloxy-1′-alkyloxycarbonyl-methylidene)-5(R)-[(1R)-menthyloxy]-γ-butyrolactones were synthesized and characterized in good to excellent yields via O-alkylation of (4R,5R)-(?)-4-ethoxyoxalyl-5-[(1R)-menthyloxy]-γ-butyrolactone with alkyl halides in the presence of K₂CO₃ in acetone at room temperature.     

Stereoselective synthesis and absolute configuration of (1′R,3R,4R)-4-acetoxy-3-(2′,2′,2′-trifluoro-1′-hydroxyethyl)azetidin-2-one

The title compound 3, an intermediate in the synthesis of fluorocarbapenems, is obtained with high stereocontrol by the condensation of (R)-(+)-ethyl 4,4,4-trifluoro-3-hydroxybutanoate with N-trimethylsilyl cinnamylidenimine. X-Ray diffraction analysis of the condensation product and chemical correlations allowed the unambiguous determination of the absolute configuration.