A new synthesis of potent antitumor saponin OSW-1 via Wittig rearrangement

OSW-1 and its analogues in which thiophene ring was introduced at the side chain were synthesized employing Wittig rearrangement of 17E(20)-ethylidene-16α-(4′-methyl-2′-thienyl)methyloxy steroid. The synthesis required nine steps from the known 17E(20)-ethylidene-16α-hydroxy steroid in 15.6% overall yield.     

Convergent synthesis of stereoisomers of THF ring moiety of acetogenin thiophene analogue and their antiproliferative activities against human cancer cell lines

The convergent synthesis of thiophene-3-carboxamide analogues of annonaceous acetogenins was accomplished through the asymmetric alkynylation of a 2-formyl THF ring fragment with an alkyne having a thiophene ring as the key step. Eight stereoisomers of the THF ring moiety were synthesized by this convergent route and their antiproliferative activities against 39 human cancer cell lines were evaluated. It was revealed that derivatives having the threo configuration between C17–C18 positions showed more potent activities than the corresponding erythro ones.     

Development in synthesis and electrochemical properties of thienyl derivatives of carbazole

A convenient and higher yielding synthetic route to N-alkyl-bis(thiophene)- and N-alkyl-bis(ethylenedioxythiophene) carbazole derivatives is reported and their aggregation, and electrochemical properties are characterized. The key step in the synthesis of this group of compounds has been the Stille-type coupling reaction between the N-alkyldibromocarbazole and tin derivatives of thiophene or ethylenedioxythiophene, as the best way for preparation of conjugated N-alkylcarbazole derivatives. For this group of compounds we also present an electrochemical polymerization effect.     

Versatile synthesis of 3,4-b diheteropentalenes

We describe a new route for the synthesis of thieno[3,4-b]thiophene, alkyl derivatives thereof, seleno[3,4-b]thiophene, and thieno[3,4-b]furan made from inexpensive starting materials, such as thiophene-2-carboxylic acid and furan-2-carboxylic acid. Such fused heterocycles are of great interest for low band gap organic semiconductors and applications including OLEDs, organic photovoltaic cells, and electrochromics.     

Recent advances in the synthesis of benzo[b]thiophene fused polycyclic derivatives: Strategies and reactions

Benzo[b]thiophene fused compounds with a unique active heterocyclic skeleton have wide applications in the fields of medicinal chemistry, organic synthesis, and organic functional materials, which resulted in rapid development of many efficient methods for the construction of benzo[b]thiophene-fused heterocycles in recent years. Among these methods, the domino reaction of benzo[b]thiophene derivatives is a practical and powerful synthetic route to access benzo[b]thiophene-fused heterocycles by virtue of the particularity of sulfur atom. This review summarizes the latest developments in the construction of benzo[b]thiophene-fused heterocycles by ring formation at the C2-C3-position of benzo[b]thiophene derivatives in the past decade. Additionally, this review is divided into four parts according to the four kinds of benzo[b]thiophene derivatives used, including thioaurone, thioisatin, substituted benzo[b]thiophene, and azadiene.     

Sodium halides as the source of electrophilic halogens in green synthesis of 3-halo- and 3,n-dihalobenzo[b]thiophenes

A convenient methodology for the synthesis of mono- and di-halogenated benzo[b]thiophenes is described herein, which utilizes copper(II) sulfate pentahydrate and various sodium halides in the presence of substituted 2-alkynylthioanisoles. The proposed method is facile, uses ethanol as a green solvent, and results in uniquely substituted benzo[b]thiophene structures with isolated yields up to 96%. The most useful component of this methodology is the selective introduction of bromine atoms at every available position (2–7) around the benzo[b]thiophene ring, while keeping position 3 occupied by a specific halogen atom such as Cl, Br or I. Aromatic halogens are useful reactive handles; therefore, the selective introduction of halogens at specific positions would be valuable in the targeted synthesis of bioactive molecules and complex organic materials via metal-catalyzed cross coupling reactions. This work is a novel approach towards the synthesis of dihalo substituted benzo[b]thiophene core structures, which provides a superior alternative to the current methods discussed herein.     

Efficient synthesis and antioxidant activity of coelenterazine analogues

A convenient and highly convergent method for the synthesis of new imidazo[1,2-a]pyridine-based coelenterazine analogues is reported. The imidazo[1,2-a]pyridine core was constructed through a condensation between 2-aminopyridine analogues and arylglyoxals. Additionally, a new approach to the synthesis of benzylglyoxals was introduced. The imidazo[1,2-a]pyridines display moderate antioxidant activities at a low micromolar level in 2,2-diphenyl-1-picrylhydrazyl (DPPH).     

Exploring the functionalisation of the thieno[2,3-d]pyrimidinedione core: Late stage access to highly substituted 5-carboxamide-6-aryl scaffolds

The thieno[2,3-d]pyrimidinedione core is found as a component in a range of pharmaceutically active compounds, however, synthetic approaches to these scaffolds rely on access to functionalised, highly substituted thiophenes. Here we describe a new approach for the preparation of 5-carboxamide-6-aryl analogues that involves a two-step synthesis of the thieno[2,3-d]pyrimidinedione core from a readily available mercaptouracil derivative. Thio-alkylation with ethyl 3-bromopyruvate, followed by cyclisation and dehydration mediated by polyphosphoric acid allowed the scalable synthesis of the thieno[2,3-d]pyrimidinedione unit. The late-stage functionalisation of this core motif via bromination of the thiophene ring and a subsequent Suzuki-Miyaura reaction as the key steps permitted access to a novel library of 5-carboxamide-6-aryl analogues. The physicochemical properties of these compounds were determined, generating an insight into the potential bioavailability of these scaffolds. Based on these results, a selection of the novel 5-carboxamide-6-aryl analogues were tested as lactate uptake inhibitors of monocarboxylate transporters 1, 2 and 4 in Xenopus oocytes.     

The synthesis and physical evaluation of 5-alkoxy-1,3-thiazoles prepared via Lawesson's reagent-mediated cyclisation of α-benzamido esters

The synthesis of the first series of 5-alkoxy-1,3-thiazole-based liquid crystals is reported. The aforementioned liquid crystals were synthesised through a Lawesson's reagent-mediated cyclisation of appropriate α-benzamido esters. This methodology was found to be highly efficient, even on a large scale, and the resulting 5-alkoxy-1,3-thiazoles could be purified without the use of column chromatography. The synthesis and mesomorphic properties of a family of 5-alkoxy-2-(4-cyanophenyl)-1,3-thiazole liquid crystals prepared via this approach are discussed and compared with their thiophene and phenyl analogues.     

Activity of catalysts in thiophene synthesis from furan and hydrogen sulfide

Thiophene synthesis from furan and H₂S over acid catalysts is reported. Proton donor catalysts are low-active, nonselective, and prone to deactivation. Alumina-supported catalysts having Lewis acid sites, such as alumina-supported catalysts, are more efficient. With these catalysts, the thiophene formation rate per Lewis acid site increases with increasing site strength. It is assumed that the reaction proceeds via the formation of a surface intermediate consisting of an acid site bonded to an α carbon atom of the furan ring and an H₂S molecule nondissociatively adsorbed on a basic site. At atmospheric pressure, T = 250–450°C, initial furan concentrations of 1–20 vol %, and H₂S/furan = 0.4–20 (mol/mol), the thiophene formation reaction is first-order with respect to both reactants and its rate constant increases with increasing temperature. The thiophene formation rate depends on the H₂S/furan molar ratio. Under optimal conditions, the thiophene yield is 95–98 mol % and the thiophene formation rate is high.     

Application of directed metalation in synthesis. Part 4: Expedient synthesis of substituted benzo[b]thiophene and naphthothiophene

A short, simple and inexpensive synthesis of several diversely substituted benzo[b]thiophenes and one naphthothiophene is described. The method involves introduction of methylsulfanyl group ortho- to the amide function of readily available N,N-diethylamides of aryl carboxylic acid by directed metalation. Thioindoxyls, obtained in high yields through side-chain deprotonation and cyclisation in one pot, are reduced to benzo[b]thiophene or napthothiophene.     

Biocatalytic and chemical investigations in the synthesis of sucrose analogues

Herein, we report about the synthesis of sucrose analogues, obtained by two different approaches: a chemical and an enzymatic. The one step synthesis of the sucrose analogues with the exo-fructosyltransferase (EC 2.4.1.162) from Bacillus subtilis NCIMB 11871, which transfers the fructosyl residue of the substrate sucrose to the monosaccharide acceptors galactose, mannose, xylose and fucose, has been developed. Effects in the fructosylation by variation of the positions of the hydroxyl-groups in glycopyranoside acceptors have been studied in respect to their acceptor properties. In contrast, the chemical equivalent nonenzymatic organic synthesis of galacto-sucrose and manno-sucrose has been achieved including six synthetic steps.     

One-step synthesis of [1]benzothieno[3,2-b][1]benzothiophene from o-chlorobenzaldehyde

Simple one-step synthesis of [1]benzothieno[3,2-b][1]benzothiophene (BTBT) from commercially available o-chlorobenzaldehyde is reported. The procedure is also applicable to the synthesis of dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (DNTT).     

The second-generation synthesis of BICMAP analogues

We previously reported the synthesis of BICMAP (1a) via 6-diphenylphosphino-2,3-dihydrobenzofuran as a key intermediate. However, we did not successfully synthesize BICMAP analogues via a similar synthetic route. Herein we report the second-generation synthesis of BICMAP and its derivatives via diethylphosphonate as a key intermediate.     

Total synthesis of the marine alkaloid halitulin

The structure of the strongly cytotoxic marine alkaloid halitulin (1) has been confirmed by total synthesis and its absolute configuration determined as (15S). The synthesis follows a strategy previously reported by one of us and uses an efficient preparation of the quinoline-7,8-diol unit by modified Baeyer-Villiger and Skraup reactions. The O-benzyl protecting groups were removed in the last step of the synthesis by transfer hydrogenolysis without concomitant reduction of the quinoline ring. The method can be applied for the synthesis of halitulin analogues.     

Investigation,optimization and synthesis of sulfamoyloxy-linked aminoacyl-AMP analogues

Aminoacyl-tRNA synthetases (aaRSs) constitute a family of enzymes that transfer amino acids to their corresponding tRNA molecules to form aminoacyl-tRNAs and have been validated as potential drug targets. Sulfamoyloxy-linked aminoacyl-AMP analogues are potent inhibitors of aaRSs. In this article, we report the synthesis of several new sulfamoyl analogues of aa-AMP that up to now have been difficult or even impossible to prepare with current synthetic strategies. The developed synthetic strategy relies on performing the synthesis under neutral conditions followed by global deprotection using catalytic hydrogenation affording the desired 5′-O-(N-aminoacyl)sulfamoyladenosine compounds.     

Total synthesis of dysiherbaine

An efficient total synthesis of dysiherbaine, a potent and subtype-selective agonist for ionotropic glutamate receptors, has been achieved. An advanced key intermediate in the previous synthesis of neodysiherbaine A and its analogues was selected as the starting point, and cis-oriented amino alcohol functionality on the tetrahydropyran ring was installed by using an intramolecular S_N2 cyclization of N-Boc-protected amino alcohol. The amino acid appendage was constructed by catalytic asymmetric hydrogenation of enamide ester.     

Efficient synthesis of 1,4-dihydronaphthalenelignans from 5-methylene-4-substituted-2(5H)-furanones and a concise synthesis of solafuranone

A short synthetic strategy for synthesis of lignan analogues involving 5-methylene-4-substituted-2(5H)-furanones as the key intermediates has been developed. Various lignans including the natural product solafuranone and analogues of dihydrotaiwanin C and deoxydehydropodophyllotoxin were synthesized in good yields.     

A short, concise synthesis of queuine

A short, concise synthesis of queuine was accomplished in a 36% overall yield through a convergent scheme utilizing a reductive amination as the penultimate step. The synthesis demonstrates the utility of silylation to facilitate reactions of various pyrrolo[2,3-d]pyrimidine intermediates, and offers the possibility of easily accessing related pyrrolo[2,3-d]pyrimidines as well as making additional analogues of queuine.     

Total synthesis of farylhydrazones A and B

Herein we report a concise total synthesis of farylhydrazones A and B, naturally occurring phenylhydrazones recently isolated from cultures of the Cordyceps-colonizing fungus Isaria farinosa, completed in six and five steps respectively starting from 2-nitrobenzoic acid. The synthesis is completely scalable, and highly convergent—making it adaptable for the preparation of analogues and investigation into the biological activity of these unique natural products.