Systematic approach to the chemical synthesis of arabidopyrones,the unique α-pyrones of Arabidopsis metabolites

Abstract

Total synthesis of two arabidopyrones, iso-arabidopyl alcohol (1) and iso-arabidopic acid (2) isolated from Arabidopsis thaliana was achieved for the first time using Claisen condensation and Wittig reaction as the key steps. In addition, arabidopic acid (4) was synthesized from the methyl ester of arabidopyl alcohol (3). Thus, chemical synthesis of the unique natural α-pyrones 1–4 was accomplished with a short synthetic route by a systematic approach from readily available substances.     

Eco-friendly synthesis of 2-azetidinone analogs of isonicotinic acid hydrazide

Abstract

2-Azetidinones possess broad and potent activity due to presence of β-lactam ring and has been established as one of the biologically important scaffolds. The synthesis of N-(4-aryl-2-oxoazetidinone)-isonicotinamide by novel methods of stirring and sonication are described. The conventional method for synthesis of 2-azetidinones involves use of Dean–Stark water separator for the removal of water from the reaction with long reaction time (12–16 h reflux) at a very low temperature (?70 to ?90°C). The microwave method reported requires inert atmosphere of nitrogen gas for the synthesis of 2-azetidinones. We report herein the synthesis of 2-azetidinone analogs of isonicotinic acid hydrazide by novel green route methods of sonication and stirring using molecular sieves. Results indicate that higher yields and shorter reaction times can be achieved by employing novel green route methods of synthesis.     

Inhaltsstoffe des Osmanthus-Absolues. 1. Mitteilung: 2,5-Epoxy-megastigma-6,8-dien

Constituents of Osmanthus Absolute, Ist communication:2,5-Epoxy-megastigma-6,8-dienes Besides some further ionone derivatives we identified two new bicyclic oxacompounds ( 1a / 1b ) of the megastigmane type in the Osmanthus absolute. Isolation, special features of their spectral datas and synthesis starting from ethyl α-safranate are described. The synthetic pathway choosen allowed the additional identification of four substances occurring in the same natural substrate, because some synthetic by-products formed int he reaction sequence exhibited corresponding spectra and GLC. retention as the hitherto unknown components of the Osmanthus absolute.     

Synthesis of New bis-Iminocoumarins by Schmidt Reaction Catalyzed by Ion-Exchange Resins

Abstract

A new synthetic route to bis-iminocoumarins is proposed which involves the synthesis of iminocoumarins from reaction of 2-hydroxybenzaldehydes with arylacetonitriles and their coupling with aromatic diamines. Ion-exchange resins were used as catalysts in both steps of this synthesis. The reaction parameters were varied and obtained using Amberlyst 15 resin in cyclohexane at 80°C.     

Synthesis of Eupolauridine and Its Benzo-Annulated Derivative

The unique diazafluoranthene alkaloid eupolauridine (1) was synthesized by a three-step route utilizing as the initial step the thermal rearrangement of the oxime O-crotyl ether 12, which afforded onychine (2). Bracher pyridine synthesis procedure subsequently converted 2 into 1. On the other hand, Friedländer reaction was employed for the synthesis of 3, which is a benzo-annulated derivative of eupolauridine (1).     

Synthesis of dendritic polyamide with protected amino functional groups in the periphery

A homologous series of first-to third-generation dendritic polyamides 2a, 3, and 5 with tris(aminoethyl) amine (TREA) as the core and the protected amino functional groups at the periphery were synthesized via active ester route from “Schlüter” type dendron 1a. Their structures were characterized by ¹H-NMR and mass spectra. Based on the efficient synthesis of the first generation dendrimer 2a (yield 75%), the synthesis of second-generation dendrimer 3 was found to be more efficient via the convergent method (yield 69%), while the mixed strategy was applied efficiently for the synthesis of the higher generation dendrimer 5 (yield 37%). The overall yield for the third generation dendrimer 5 from Schlüter dendron is 12%. __________ Translated from Huaxue Tongbao (Chemistry), 2005, 68(12) (in Chinese)     

A new megastigmane sulphoglycoside and polyphenolic constituents from pericarps of Garcinia mangostana

A megastigmane sulphoglycoside together with three phenolic compounds were isolated from the water-soluble fraction of the pericarps of Garcinia mangostana. The structure of the new compound was determined as 4-O-sulpho-β-d-glucopyranosyl abscisate (1) by spectroscopic data. Proanthocyanidin A2 (2) showed potent α-glucosidase inhibitory and DPPH scavenging activities with IC₅₀ values of 3.46 and 11.6 μM, respectively.     

Recent advances and perspectives on the synthesis and C–H bond functionalization of quinoxalin-2(1H)-one

Abstract

Over the past few decades, quinoxalin-2(1H)-one derivatives are serving as active components in diverse families of drugs such as antimicrobial, anticancer, antithrombotic agents and protein kinase inhibitor. Previously, significant attention has been marked for its synthesis and recent years have also observed an upsurge in the modification of this scaffold as well as its functionalization. This review (2008–2020) focused on selective C–H bond functionalization namely arylation, amination, acylation, amidation, alkylation, benzylation, alkoxycarbonylation, cyanoalkylation and phosphorylation etc. at C-3 position of quinoxalin-2(1H)-one. Additionally, alternative complimentary route (radical cyclization protocol) for its synthesis part is well elaborated herein. We also briefly summarized the mechanistic pathway of the C–H bond functionalization approach.     

Stereoselective total synthesis of paecilomycin E and F and its two congeners Cochliomycin C and 6-epi-Cochliomycin C

An efficient and concise approach to the total synthesis of Paecilomycins E (1) and F (2), Cochliomycin C (4) and 6-epi-Cochliomycin C (3) is described. The synthesis involves novel route to the synthesis of Paecilomycin E and F and further conversion to Cochliomycin C and 6-epi-Cochliomycin C. Olefin metathesis and base promoted macro lactonization being the key reactions followed by chlorination to achieve target Cochliomycin C and 6-epi-Cochliomycin C.     

Regio- and Stereoselective Synthesis of γ-Alkylidenebutenolides by Cyclization of Dilithiated 1,3-Dicarbonyl Compounds with N,N′-Dimethoxy-N,N′-dimethylethane- diamide

The remarkably simple synthesis of γ-alkylidenebutenolides 3 is achieved by cyclization of the dilithiated 1,3-dicarbonyl compounds 1 with N,N′-dimethoxy-N,N′-dimethylethanediamide ( 2 ). This regio- and stereoselective cyclization provides a route to a wide range of butenolides, which are of pharmacological relevance and of importance for natural product synthesis.     

Flow reactor synthesis of unsymmetrically substituted p-terphenyls using sequentially selective Suzuki cross-coupling protocols

ABSTRACT

Synthetic procedures, based on integrated flow chemical methods, have been developed for the sequential chemo-selective Suzuki–Miyaura cross-coupling of 1,4-dibromo-2-nitrobenzene (1) with various arylboronic acids. The first Suzuki coupling step used a phosphine-(ligand)-free palladium catalyst at room temperature and gave regio-selective coupling of (1) at the ortho-position to the nitro group. The bromo-biaryl product was then directly subjected in situ to a second coupling step, using different arylboronic acids, as a continuous in-flow operation. Based on this methodology, a number of unsymmetrically substituted p-terphenyl compounds were synthesized in excellent overall yields. This approach provides a convenient route to this class of compounds, and is suited for the generation of targeted chemical libraries, or the synthesis of precursors of biologically active natural product analogues that contain the p-terphenyl core. During the first coupling step, dimerization at low levels of the bromo-biaryl intermediate occurred, leading to formation of quaterphenyl compounds.     

First asymmetrically beta-tetrasubstituted porphyrin-based discotic lamellar liquid crystal

The synthesis and liquid crystalline properties of a new asymetrically tetrasubstituted porphyrin, namely 2,4-bis[2-(o-didodecyloxyphenoxycarbonyl)ethenyl]-6,7-bis[2-(m -didodecyloxycarbonyl)ethyl]-1,3,5,8-tetramethylporphyrin, 1 (figure 1), obtained from a commercially available porphyrin, hemin 2, are reported here. The synthetic route basically consists of two reactions: on the one hand, one esterification of the two propionic acid groups in positions 6 and 7 in the hemin 2 with the phenol 12, and on the other hand, a Heck-type reaction between the two vinyl groups in positions 2 and 4 of the hemin 2 and the iodo-aryl derivative 9. This is the first example of a porphyrin-based discotic liquid crystal which is neither symmetrically substituted nor prepared via total synthesis from monopyrrole units. It exhibits a well-defined enantiotropic discotic lamellar mesophase (D_L) in a range of temperature from -2°C to the clearing point at 70°C. This interval includes room temperature, which makes this molecule suitable for a wide variety of applications.     

Improved Routes for the Preparation of Pentaerythritol Mono‐O‐benzyl Ether

Two new efficient routes for the synthesis of pentaerythritol monobenzyl ether are described. In one route, the known mono‐O‐benzylidenepentaerythritol (5) is selectively benzylated via its dibutylstannylene acetal and then the benzylidene acetal is hydrolized. In the other route, compound 5 is reduced directly to the monobenzyl ether using EtAlCl₂‐Et₃SiH.     

Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT

The stereocontrolled synthesis of methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (EC, 1), methyl α-L-rhamnopyranosyl-(1→3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (B(E)C, 3) and methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyl-α-L-rhamnopyranoside (11) and 8 afforded the fully protected αE-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding βE-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding βE-disaccharide, namely, methyl β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (βEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the αE and βE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required αE-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2,3-di-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.     

Linear Synthesis of the Methyl Glycosides of Tetra- and Pentasaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT

Starting from the known methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2-O-benzoyl-α-L-rhamnopyranoside, the stepwise linear syntheses of methyl α-L-rhamnopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→ 3)-[α-D-glucopyranosyl-(1→ 4)]-α-L-rhamnopyranoside (AB(E)C, 4), and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→ 2)-α-L-rhamnopyranosyl-(1→ 3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (DAB(E)C, 5) are described; these constitute the methyl glycosides of a branched tetra- and pentasaccharide fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a, respectively. The chemoselective O-deacetylation at position 2_B and/or 2_A of key tri- and tetrasaccharide intermediates bearing a protecting group at position 2_C was a limiting factor. As such a step occurred once in the synthesis of 4 and twice in the synthesis of 5, the regioselective introduction of residue A on a B(E)C diol precursor (12) and that of residue D on an AB(E)C diol precursor (19) was also attempted. In all cases, a trichloroacetimidate donor was involved. The latter pathway was found satisfactory for the construction of the target 4 using the appropriate tri-O-benzoyl rhamnosyl donor. However, attempted chain elongation of 12 using 2-O-acetyl-3,4-di-O-benzyl-α-L-rhamnopyranosyl trichloroacetimidate (8) resulted in an inseparable mixture which needed to be benzoylated to allow the isolation of the target tetrasaccharide. Besides, condensation of the corresponding tetrasaccharide acceptor and the N-acetylglucosaminyl donor was sluggish. As the target pentasaccharide was isolated in a poor yield, this route was abandoned.     

Synthesis,antimicrobial evaluation and docking study of triazole containing triaryl-1H-imidazole

An efficient route for the synthesis of triazole containing triaryl-1H-imidazole (3a–3r) was achieved involving multicomponent condensation of triazole aldehydes, ammonium acetate and 1,2-dicarbonyl compounds in glacial acetic acid. The structure of newly synthesized imidazoles was established by the FTIR, HRMS and NMR spectra. All the compounds displayed considerable antimicrobial activity against fungal and bacterial strains. The triazolyl imidazole 3p was substantially potent against P. aeruginosa (0.0113?µmol/mL), A. niger (0.0113?µmol/mL) and C. albicans (0.0056?µmol/mL) wherein triazolyl imidazoles 3i was found to be more potent against B. subtilis (0.0122?µmol/mL) & A. niger (0.0121?µmol/mL); and compound 3r was also found to be more potent against S. epidermidis (0.0117?µmol/mL) & C. albicans (0.0058?µmol/mL). As a result of docking studies, the binding affinity of the compound 3o was –9.6?kcal/mol which was even more in comparison to the binding affinity of co-crystallized ligand CBN (–9.4?kcal/mol).     

Synthesis of Chiral Aminocyclopropanes by Rare‐Earth‐Metal‐Catalyzed Cyclopropene Hydroamination

The search for efficient and selective routes for the synthesis of chiral aminocyclopropane derivatives is of great interest and importance as these structures are important components of biologically active natural products and pharmaceuticals. We herein report the enantioselective intermolecular hydroamination of substituted cyclopropenes with various amines catalyzed by chiral half‐sandwich rare‐earth‐metal complexes. This method constitutes a 100 % atom‐efficient route for the synthesis of a variety of chiral α‐aminocyclopropane derivatives in high yields (up to 96 %) and excellent stereoselectivity (up to >20:1 d.r. and 99 % ee) under mild reaction conditions (25 °C).     

Debilosides A–C: Three New Megastigmane Glucosides from Equisetum debile

Debilosides A–C ( 1 – 3 ), three new megastigmane glucosides, were isolated from the whole plant of Equisetum debile, together with the four known constituents blumenol A, corchoinoside C, sammangaoside A, and (3S,5R,6R,7E,9S)‐9‐[(β‐D ‐glucopyranosyl)oxy]megastigm‐7‐ene‐3,5,6‐triol ( 4 ). Their structures were elucidated on the basis of in‐depth spectroscopic analyses including 2D‐NMR techniques.     

Radical Cyclization Route to the Stereoselective Synthesis of (+)‐trans‐Cognac Lactone and (+)‐trans‐Aerangis Lactone

Stereoselective total synthesis of two chiral lactones, (+)‐trans‐cognac lactone (1b) and (+)‐trans‐aerangis lactone (2c), has been achieved from the same intermediate using a radical‐based cyclization route.     

Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A−F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation

Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt-catalyzed hydrovinylation as the chirogenic step. Other noteworthy C−C bond forming transformations include diastereoselective Lewis acid-mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4-methyl-styrene the anti-tubercular agent (+)-erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti-inflammatory activity (inhibition of LPS-induced NF-κB activation) as a natural mixture of pseudopterosins A−D or iso-pseudopterosin A, prepared by β-D-xylosylation of the synthetic aglycone.