A facile and highly stereoselective synthesis of (2E)-, (2E,4E)-unsaturated amides and related natural products

A facile synthesis of (2E)-, (2E, 4E)-unsaturated amides was achieved via arsonium bromides with high stereoselectivity. Its application to the synthesis of related natural products 4 and 5 is also reported.     

Stereoselective synthesis of cis- or trans-3,5-disubstituted pyrazolidines via Pd-catalyzed carboamination reactions: use of allylic strain to control product stereochemistry through N-substituent manipulation

The stereoselective synthesis of either trans- or cis-3,5-disubstituted pyrazolidines is accomplished via Pd-catalyzed carboamination reactions of unsaturated hydrazine derivatives. The products are obtained in good yield with up to >20:1 diastereoselectivity. Stereocontrol is achieved by modulating the degree of allylic strain in the transition state for syn-aminopalladation through a simple modification of the substrate N(2)-substituent. The pyrazolidine products can be further transformed to 3,5-disubstituted pyrazolines via deprotection/oxidation, or to substituted 1,3-diamines via N-N bond cleavage.     

Mixed disproportionation versus radical trapping in titanocene(III)-promoted epoxide openings

The formation of either deoxygenation products or allylic alcohols from epoxides is observed when these substrates are treated with Cp₂TiCl under anhydrous conditions. It seems that processes via trisubstituted radicals give allylic alcohols whereas processes via disubstituted radicals may give deoxygenation products or allylic alcohols depending on the structure of the original epoxide. This method allows a controlled access to these functional groups, providing a useful tool in organic synthesis. A mechanistic discussion for these transformations is reported.     

An intramolecular oxo Diels-Alder approach to 1-oxo-1,2,3,3a,4,7a-hexahydro-pyrano[3,4-c]pyrrole-4-carboxylic acid ethyl esters

The diastereoselective synthesis of a series of 1-oxo-1,2,3,3a,4,7a-hexahydro-pyrano[3,4-c]pyrrole-4-carboxylic acid ethyl esters via an oxo Diels-Alder reaction is described. Ab initio calculations predicted the products of the exo cycloaddition to be the thermodynamic products while the products resulting from the endo cycloaddition were predicted to be the kinetic products. The calculations were born out by experimental data.     

不同制备方法对BiOCl材料的形貌、结构与光催化性能的影响研究

对比采用溶剂热合成、传统固相合成与溶胶-凝胶合成技术,制备了四方相BiOC1和Nd3+掺杂BiOCl光催化材料.运用X射线粉末衍射(XRD)、扫描电子显微镜(SEM)及紫外-可见吸收光谱(UV-Vis),研究了不同合成方法所制备BiOCl材料的相结构、形貌和紫外-可见光吸收性能;并以甲基橙溶液为模拟废水,研究了不同方法所制备的BiOCl材料的光催化性能.结果表明:溶剂热合成的BiOCl是由纳米片组装成粒径小于1μm微球,紫外-可见吸收边为335 nm;固相合成所得BiOCl结晶度较高,其片状颗粒粒径约为6μm,紫外-可见吸收边为430n m;溶胶-凝胶合成法制得BiOCl片状颗粒粒径约为3～4 μm,紫外-可见吸收边为430 nm.进一步地对比研究了稀土离子Nd3+掺杂前后BiOCl样品的结构、紫外-可见光吸收特性,可以发现,Nd3+掺杂后样品的相结构及形貌均无变化,但吸收边均发生不同程度的红移,以溶胶-凝胶法制得的样品效果最为明显,并具有最优的光催化性能.     

Palladium-catalyzed synthesis of 1,3,4-alkatrien-2-yldihydrofurans from 2,3-allenylacetylacetates and propargylic carbonates and their application to synthesize polysubstituted dihydrofurylcyclopentenones

An efficient route to 1,3,4-alkatrien-2-yldihydrofurans via a highly chemo- and regioselective palladium(0)-catalyzed coupling-cyclization reaction of 2-(2′,3′-allenyl)acetylacetates with propargylic carbonates was reported. The reaction proceeded smoothly under neutral conditions, affording the O-attacked five-membered products with a 1,3,4-trienyl substituent exclusively in good to excellent yields. The products can be efficiently applied to the synthesis of polysubstituted 2-(dihydrofuryl)cyclopentenone derivatives via a catalytic Pauson-Khand reaction under ambient conditions.     

Asymmetric synthesis of cytotoxic sponge metabolites R-strongylodiols A and B

The asymmetric synthesis of the marine sponge natural products, R-strongylodiols A 1 and B 2 using a minimum protection strategy is described. The chirality of the natural products was introduced via the Noyori asymmetric reduction of ynones.     

Enantioselective sulfoxide-directed preparation of 1,2-diols from oxalic compounds: formal synthesis of the 10-membered lactone core of ascidiatrienolides and didemnilactones

The synthesis of diene 17, which is available in both possible absolute configurations is described. This diene constitutes the key intermediate of a previous synthesis of the 10-membered lactone core of the marine natural products ascidiatrienolides and didemnilactones. This intermediate is available via two successive highly diastereoselective sulfoxide-directed reductions of oxalic diamide 18.     

Studies towards complex bridged alkaloids: regio- and stereocontrolled enolate chemistry of 2,5-diketopiperazines

The substitution of symmetrical N-protected diketopiperazines (DKPs) via enolate intermediates has been studied. The enolate reactions were highly diastereocontrolled, leading to enantiopure DKP products if chiral amino acid precursors were employed, and giving racemic products, starting with centrosymmetric DKPs, even when a chiral lithium amide base was used to generate the lithium enolate. With unsymmetrical DKPs derived from proline and either alanine, phenylalanine or valine, the enolate substitution occurred with high regio- and stereoselectivity on the proline residue. This enabled the synthesis of substituted DKPs that could be cyclised via cationic processes to give the bicyclo[2.2.2]diazaoctane core structure present in paraherquamide and stephacidin natural products.     

One-pot conversion of phenols to anilines via Smiles rearrangement

A convenient one-pot synthesis of phenols to anilines using 2-chloroacetamide/K₂CO₃/DMF system catalyzed by KI via Smiles rearrangement has been described. The synthesis of extensive amino aromatic products from phenols containing electron withdrawing group, has been performed in moderate to excellent yields to demonstrate the potentiality of this method in bio-medicinal and pharmaceutical applications.     

Molecular recognition of diketide substrates by a β-ketoacyl-acyl carrier protein synthase domain within a bimodular polyketide synthase

Background: Modular polyketide synthases (PKSs) are large multifunctional proteins that catalyze the biosynthesis of structurally complex bioactive products. The modular organization of PKSs has allowed the application of a combinatorial approach to the synthesis of novel polyketides via the manipulation of these biocatalysts at the genetic level. The inherent specificity of PKSs for their natural substrates, however, may place limits on the spectrum of molecular diversity that can be achieved in polyketide products. With the aim of further understanding PKS specificity, as a route to exploiting PKSs in combinatorial synthesis, we chose to examine the substrate specificity of a single intact domain within a bimodular PKS to investigate its capacity to utilize unnatural substrates.Results: We used a blocked mutant of a bimodular PKS in which formation of the triketide product could occur only via uptake and processing of a synthetic diketide intermediate. By introducing systematic changes in the native diketide structure, by means of the synthesis of unnatural diketide analogs, we have shown that the ketosynthase domain of module 2 (KS2 domain) in 6-deoxyerythronolide B synthase (DEBS) tolerates a broad range of variations in substrate structure, but it strongly discriminates against some others.Conclusions: Defining the boundaries of substrate recognition within PKS domains is crucial to the rationally engineered biosynthesis of novel polyketide products, many of which could be prepared only with great difficulty, if at all, by direct chemical synthesis or semi-synthesis. Our results suggest that the KS2 domain of DEBS1 has a relatively relaxed specificity that can be exploited for the design and synthesis of medicinally important polyketide products.     

A chemoselective Reformatsky–Negishi approach to α-haloaryl esters

A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)₂ and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.     

A Simple Preparation of 2-Pyrone Structural Unit

The synthesis of 4-substituted 2(5H)-furanones via organosilicon intermediates has been reported from this laboratory.¹ This method gave possibilities to extend the synthesis to include 2-pyrone species (e. g. 1), which are structure units of some natural products.     

Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines

Ring-closing olefin metathesis (RCM) has been applied to the efficient synthesis of densely and diversely substituted pyridine and pyridazine frameworks. Routes to suitable metathesis precursors have been investigated and the scope of the metathesis step has been probed. The metathesis products function as precursors to the target heteroaromatic structures via elimination of a suitable leaving group, which also facilitates earlier steps by serving as a protecting group at nitrogen. Further functionalisation of the metathesis products is possible both prior to and after aromatisation. The net result is a powerful strategy for the de novo synthesis of highly substituted heteroaromatic scaffolds.     

I2-mediated α-selective Ferrier glycosylation approach to synthesis of O-glycosyl amino acids

I₂ is an effective promoter for the synthesis of 2,3-unsaturated glycosides via Ferrier glycosylation. This reaction was used in the present work for the synthesis of O-glycosylated Fmoc amino acid building blocks. This metal-free reaction afforded the desired products with good to excellent yields with good α-selectivity.     

A strategy for the synthesis of the fargenone/fargenin family of natural products: synthesis of the tricyclic core

A synthesis of the core ring structure of the fargenin/fargenone family of natural products is presented. The general strategy is based upon biosynthetic speculation and exploits a cascade reaction, which transforms a spirocyclic dienone into the core ring system via a deprotonation-oxy-Michael-Wittig olefination sequence. This study represents the first synthesis work towards this family of natural products.     

Condensation of Cp2TiCI2 with Tetraamines

The synthesis of titanium polyamines from tetraamines is general and rapid. Systems utilizing equimolar quantities of reactants produce linear products, whereas tri- and tetra-substitution occurs when excess Cp₂TiCl₂ is used. The products exhibit moderate high-temperature stability but poor low-temperature stability, with degradation occurring via nonoxidative routes to ca. 200°C, and by oxidative routes in air at higher temperatures.     

Cascade polycyclization: exploration of a convergent route to access various tricyclic and tetracyclic products related to sterols

The expedient synthesis of tricyclic and tetracyclic compounds via a cascade polycyclization methodology is described. Nazarov substrates (II) containing two Michael acceptors and a cyclohexenone ester (I) underwent cycloaddition followed by intramolecular 1,4-addition to furnish, in a highly stereoselective manner, tricyclic and tetracyclic products (III). Such compounds are interesting intermediates for the synthesis of polycyclic natural and unnatural products.     

Semi-synthesis of a novel hybrid isoxazolidino withaferin via chemoselective and diastereoselective 1,3-dipolar nitrone cycloaddition reaction

Abstract

A facile, atom-economic synthesis of isoxazilidino withaferin, a novel hybrid of withaferin A, has been accomplished via two-step reaction of nitrone synthesis followed by nitrone 1,3-dipolar cycloaddition. The reaction is highly chemoselective (preferential reaction only on one of the two double bonds present on withaferin A) and diastereoselective affording exclusively the cis-fused products. The structure was determined by detailed analysis of 1D, 2D NMR and mass spectral data.     

A new domino Knoevenagel-hetero-Diels-Alder reaction: an efficient catalyst-free synthesis of novel thiochromone-annulated thiopyranocoumarin derivatives in aqueous medium

An efficient catalyst-free synthesis of novel pentacyclic thiochromone-annulated thiopyranocoumarin derivatives is achieved via domino Knoevenagel-hetero-Diels-Alder reaction of 4-hydroxy dithiocoumarin and O-acrylated salicylaldehyde derivatives in H₂O as solvent. The products are formed in good yields with high regio- and stereo-selectivity.