Stereoselective synthesis of selenosteroids

A stereoselective synthesis of selenosteroids 4 and 5 has been achieved. Starting from commercial available cholesterol 1, followed by asymmetric epoxidation, and subsequently, by stereoselective epoxide ring opening, employing a selenium nucleophilic species, the correspondent products were afforded in high yields. The compounds were being evaluated for their biological activity and as a chiral pool for asymmetric transformations.     

Stereoselective synthesis and anti-HCV activity of conformationally restricted 2′-C-substituted carbanucleosides

Conformationally restricted 2′-C-azido-, hydroxy- and fluoromethyl-carbanucleosides 4b–f were efficiently synthesized via the stereoselective conversion of ketone 7 to epoxide 14, followed by the stereoselective opening of the epoxide with nucleophiles (OAc, N₃, and F), while the corresponding 2′-C-methyl-carbanucleoside 4a was synthesized via the stereoselective Grignard reaction of ketone 7 with methylmagnesium iodide as a key step. All the final nucleosides 4a–f were assayed for anti-HCV activity, but showed neither significant anti-HCV activity nor cytotoxicity in a cell-based replicon assay.     

Stereoselective intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction of N-formyl-β-nitroamides

The stereoselective intramolecular nitrile oxide cycloaddition (INOC) reaction was achieved from N-formyl-β-nitroamides, which were prepared through the Michael addition of allylic formamides to nitroalkenes, and cis-pyrroroisoxazoles and trans-piperidinoisoxazoles were obtained in a stereoselective manner.     

The total synthesis of (±)-cycloeudesmol

The highly stereoselective total synthesis of (±)-cycloeudesmol was achieved by the stereoselective cyclopropane ring formation of an epoxy alcohol ($\text{7}$) as a key reaction.     

Stereoselective diversity-oriented syntheses of functionalized saccharides from bicyclic carbohydrate 1,2-lactones

Bicyclic carbohydrate 1,2-lactones have been synthesized in only two steps and high yields by saponification and subsequent cyclization from known malonate addition products to glycals. The gluco-configured lactone serves as an important precursor for diversity-oriented syntheses. Thus, stereoselective opening of the lactone ring was realized with various nucleophiles in the presence of Sc(OTf)₃. This enabled the introduction of different substituents at the anomeric position, to afford a broad variety of 1-functionalized carbohydrates. On the other hand, stereoselective α-substitution of the gluco-configured lactone with different electrophiles and subsequent ring opening gives a collection of 2-functionalized saccharides. More than 30 products have been isolated in analytically pure form, and their configurations were unequivocally established by various NMR methods. Thus, carbohydrate 1,2-lactones are attractive precursors for the stereoselective synthesis of diverse saccharides.     

Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.     

Stereoselective Synthesis of the Optical Isomers of a New Muscarinic Receptor Antagonist,HL‐031120

We present here a practical stereoselective synthetic method to produce enantiopure isomers of a new muscarinic receptor antagonist, HL‐031120 (3‐quinuclidinyl‐2′‐cyclopentyl‐2′‐hydroxy‐2′‐phenylacetate, I). Four optical isomers were effectively by stereoselective synthesized using pivaldehyde as steric hindrance agent from the chiral starting material, (S) or (R)‐mandelic acid. The isomers were obtained with 70–76% yields in 98–99% e.e.     

A novel approach to functionalized (E)-1,4-diaryl-1-butenes by Heck reaction and their applications for the construction of dibenzylbutyrolactone lignan skeletons by radical cyclization

A highly regio- and stereoselective [Pd(allyl)Cl]₂ catalyzed Heck reaction of aryl iodides and electronically neutral terminal olefins generated in situ by fluoride induced protiodesilylation of alkenylsilanol derivatives under mild conditions has been developed. The products, viz. terminally substituted styrenes and (E)-1,4-diaryl-1-butenes were obtained in very good yields. The dibenzylbutyrolactone lignan skeletons have been prepared employing two regio- and stereoselective Bu₃SnH-mediated radical cyclization routes.     

A Novel Synthesis of the Macrocyclic Spermidine Alkaloid (+)‐(S)‐Dihydroperiphylline

A novel, short, and highly stereoselective synthesis of the macrocyclic spermidine alkaloid (+)‐(S)‐dihydroperiphylline ( 15 ) is described. The key synthetic steps were the stereoselective addition of the chiral amine 1 to the cinnamate 2 and cyclization of the bis[toluene‐4‐sulfonamide] precursor 12 in the presence of Cs₂CO₃ as a template. Unambiguous assignments of the signals in both the ¹H‐ and ¹³C‐NMR spectra of 15 were achieved by 2D NMR spectra.     

Total Synthesis of Siomycin A: Construction of Synthetic Segments

The five practical segments for the total synthesis of siomycin A, that is, the dehydropiperidine segment A ( 5 ), the pentapeptide segment B ( 3 ), the dihydroquinoline segment C ( 6 ), and the β‐phenylselenoalanine dipeptide segments D ( 7 ) and E ( 4 ), were synthesized. Segment A ( 5 ) was constructed by the coupling of the azomethine ylide and the chiral sulfinimine, followed by the stereoselective reduction of the six‐membered imine function. Segment B ( 3 ) was synthesized by the phenylselenylation of the β‐lactone, stereoselective vinylzinc addition to the chiral sulfinimine, and oxazoline–thioamide conversion. Segment C ( 6 ) was prepared by the one‐pot olefination of the tetrahydroquinoline N‐oxide using triflic anhydride and triethylamine, stereoselective reduction of the methyl ketone function, and regioselective Yb(OTf)₃‐catalyzed epoxide opening by the amino group. Segments D ( 7 ) and E ( 4 ) were synthesized by coupling of the properly protected β‐phenylselenoalanines.     

Stereoselective Metal‐Free Synthesis of β‐Amino Thioesters with Tertiary and Quaternary Stereogenic Centers

β‐Amino thioesters are important natural building blocks for the synthesis of numerous bioactive molecules. An organocatalyzed Mannich reaction was developed which provides direct and highly stereoselective access to acyclic β²‐ and β^2,3,3‐amino thioesters with adjacent tertiary and quaternary stereocenters. Mechanistic studies showed that the stereochemical course of the reaction can be controlled by the choice of the substrates. The β‐amino thioesters were further functionalized by, for example, stereoselective decarboxylation to access β^2,3‐frameworks. In addition, the value of the β‐amino thioesters was shown in coupling‐reagent‐free peptide synthesis.     

A stereocontrolled synthesis of (−)-detoxinine from l-ascorbic acid

A stereoselective synthesis of (−)-detoxinine, the core unit of the detoxifying agent detoxin D₁, is presented. The approach, characterized by the use of an inexpensive starting material and by the easy and stereoselective preparation of the key 4,5-disubstituted oxazolidin-2-one 11, proves to be a suitable alternative to the known procedures.     

Novel construction of the brassinolide side chain

A stereoselective synthesis of brassinolide, which involves construction of the side chain by a highly stereoselective aldol reaction between 20S-6β-methoxy-3α,5-cyclo-5α-pregnane-20-carboxaldehyde 2 and ketone 3 or 4 catalyzed by l-proline, is described.     

Stereoselective Synthesis of Trisubstituted Olefins

Abstract

A new method for the highly stereoselective synthesis of trisubstituted olefins is. presented. The method involves the stereoselective construction of various β-hydroxy phosphonamidates followed by their thermolysis to provide trisubstituted olefins in extremely high geometrical purity (>99/1).     

One‐Pot Stereoselective Synthesis of 2‐Acylaziridines and 2‐Acylpyrrolidines from N‐(Propargylic)hydroxylamines

The stereoselective direct transformation of N‐(propargylic)hydroxylamines into cis‐2‐acylaziridines was achieved by the combined use of AgBF₄ and CuCl. Copper salts were found to promote the transformation of the intermediary 4‐isoxazolines into 2‐acylaziridines and both 3‐aryl‐ and 3‐alkyl‐substituted 2‐acylaziridines could be prepared by using this method. Furthermore, subsequent 1,3‐dipolar cycloaddition of azomethine ylides that were generated in situ from the intermediary 2‐acylaziridines with maleimides was achieved in a stereoselective one‐pot procedure to afford the corresponding 2‐acylpyrrolidines, which consisted of an octahydropyrrolo[3,4‐c]pyrrole skeleton.     

Asymmetric synthesis of N-phenylethyl-2-phenyldecahydroquinolin-4-ones via Lewis acid catalyzed imino-Diels–Alder reaction

The asymmetric synthesis of N-phenylethyl-2-phenyldecahydroquinolin-4-ones was performed via a Lewis acid catalyzed imino-Diels–Alder reaction between the enantiopure (R)-N-phenylethylbenzylideneimine and the trimethylsilyl enol ether of acetylcyclohexene. The regio- and stereoselective formation of intermediary bicyclic enoxysilanes, followed by their stereoselective protonation was evidenced. The initial stereoselectivity was kept only if the reaction mixture was treated using controlled basic conditions. Three enantiopure title compounds were isolated with a 5–15% yield.     

Ultrasound-promoted regioselective and stereoselective synthesis of novel spiroindanedionepyrrolizidines by multicomponent 1,3-dipolar cycloaddition of azomethine ylides

A series of novel spiroindanedionepyrrolizidines have been synthesized by multicomponent 1,3-dipolar cycloaddition of a variety of (E)-3-aryl-1-(thiophen-2-yl)prop-2-en-1-ones with unstabilized azomethine ylides generated from ninhydrin and l-proline. The reactions were highly regioselective and stereoselective and were conducted with both conventional heating and ultrasonic irradiation conditions. In general, milder conditions, and moderate improvement in rates, reaction times, and yields were observed when the reactions were performed under ultrasonic conditions. The regioselective and stereoselective nature of the products was established by use of single-crystal X-ray structure and spectroscopic techniques.     

Total synthesis of (−)-funebrine via Au-catalyzed regio- and stereoselective γ-butyrolactonization of allenylsilane

The stereoselective total synthesis of (−)-funebrine from 2-butyn-1-ol was described. The crucial steps in the synthesis involved the stereoselective enolate Claisen rearrangement of the (S)-α-acyloxy-α-alkynylsilane 8, the Au-catalyzed regio- and stereoselective lactonization of the allenylsilane 7, and the Paal-Knorr pyrrole condensation using an unsymmetrical 1,4-diketone 4b.     

Nitrogen bridgehead compounds. Part 77. Addition reaction of 9-methylene-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones

Addition of bromine or thioacetic acid onto 6-methyl-9-methylenetetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones is stereoselective and gives the cis 6-Me,9-CH substituted products. Addition is also stereoselective in respect to the C(9) and C(10) centers, and gives as the primary product the erythro diastereomer, which may then undergo epimerization to the threo isomer. Relative configuration and predominant conformation of the products were determined by 1D and 2D nmr methods.     

A concise and stereoselective synthesis of the brassinolide and related compounds’ side chains

A stereoselective synthesis of brassinolide, which involves construction of the side chain by highly stereoselective aldol reaction of 20S-6β-methoxy-3α,5-cyclo-5α-pregnane-20-carboxadehyde 5 with the anion of α-silyloxy ketone 6 is described.