Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors

Application of our original photooxidation-reduction methodology to prenylated dihydroxycoumarin and trihydroxyxanthone compounds led to the corresponding ortho-(2-hydroxy-3-methylbut-3-enyl)phenol derivatives with yields ranging from 8 to 65%. In most of the reported experiments, the oxidation products distribution, after the photooxygenation step, was controlled by the competition between the large group effect and the stabilising phenolic assistance effect. We also showed that ortho-(3-hydroxy-3-methylbut-1-enyl)phenol derivatives could be considered as biogenetic precursors of 2,2-dimethylbenzopyranic structures.     

13C NMR-spectroscopy of substituted xanthones—III: Computer supported structure elucidation of polyhydroxy xanthones

A procedure for developing ¹³C NMR chemical shift additivity rules for all 136 polyhydroxy xanthones, which is based on the method of multiple linear regression analysis with dummy parameters, is reported. A computer search program is presented, which rapidly identifies unkown polyhydroxy xanthones with the help of these additivity rules. The working mode is described and its selectivity demonstrated by means of examples from literature.     

New triazole derivatives containing substituted 1, 2, 3-triazole side chains: Design,synthesis and antifungal activity

In order to discover new generation of triazole antifungal agents,a series of novel antifungal triazoles were designed and synthesized by structural simplification of our previously identified triazole-piperdine-heterocycle lead compounds.Several target compounds showed good antifungal activity with a broad spectrum.In particular,compound 7l was highly active against Candida albicans and Candida glabrata.Moreover,compound 7l showed potent in vivo antifungal efficacy in the Caenorhabditis elegans-C.albicans infection model.     

Liphagal, a Selective inhibitor of PI3 kinase alpha isolated from the sponge akacoralliphaga: structure elucidation and biomimetic synthesis

[structure: see text] Liphagal (1), a selective inhibitor of PI3K alpha, has been isolated from the marine sponge Aka coralliphaga collected in Dominica. The "liphagane" meroterpenoid carbon skeleton of liphagal (1) is new. A biomimetic total synthesis has been used to confirm the constitution of liphagal (1) and support a proposed biogenesis.     

Synthesis, characterization and theoretical interpretation of vibrational spectra of poly(2-methylbut-2-enyl thiophene-3-carboxylate)

Electroactive thiophene substituted polyacetylene derivative, namely poly(2-methylbut-2-enyl thiophene-3-carboxylate) (PMT) was synthesized. First, novel acetylene monomer was synthesized by the reaction of 3-thiophenecarboxylic acid with propargyl bromide and then polymerized with a Rh catalyst to give the corresponding polymer. FTIR and FT-Raman spectra were recorded experimentally and used for complete normal mode analysis using Wilson’s GF matrix method and Phonon dispersion of poly(2-methylbut-2-enyl thiophene-3-carboxylate). The simple non-redundant set of internal coordinates and a simplified Urey-Bradley force-field approximation was employed in normal coordinate analysis and to calculate the potential energy distribution (PED) for each fundamental vibration. The PED contribution corresponding to each of the observed frequencies shows the reliability and accuracy of the spectral analysis. Apart from detailed assignments of modes, various characteristic features of dispersion curves have also been explained as arising due to internal symmetry in energy momentum space. Predicted values of intramolecular contribution to the heat capacity of this polymer calculated by density-of-states are also being reported.     

Organocatalytic asymmetric synthesis of substituted 3-hydroxy-2-oxindoles via Morita-Baylis-Hillman reaction

We report a highly enantioselective Morita-Baylis-Hillman (MBH) reaction of isatins and acrolein to provide enantiomerically enriched 3-substituted 3-hydroxyoxindoles, which could serve as valuable synthetic building blocks. This is also the first time that a ketone has been used as the electrophile and acrolein as the nucleophile in a highly enantioselective catalytic asymmetric MBH reaction. Hatakeyama's catalyst, β-isocupreidine (1), turned out to be a powerful catalyst for this transformation.     

Computer supported structure elucidation of polymethoxy- and polyacetoxyxanthones. V—13C NMR spectroscopy of substituted xanthones

A procedure for developing ¹³C NMR chemical shift additivity rules for all 136 polymethoxyxanthones and all 136 polyacetoxyxanthones, based on multiple linear regression analysis, is reported. The influence of steric interactions between the substituents on the chemical shifts of the carbon atoms in the xanthone ring system is discussed and included in the calculations of the additivity rules for the polymethoxyxanthones. The derived chemical shift increments are implemented into the computer program SEOX 1. The extended program, SEOX 2, allows an automated structure elucidation of polyhydroxy-, polymethoxy- and polyacet-oxyxanthones. The increments are tested using the leave-one-out method in conjunction with SEOX 2, and have been found to be very suitable for this purpose.     

First synthesis of N-(3-carboxylpropyl)-5-amino-2-hydroxy-3- tridecyl-1,4-benzoquinone, an unusual quinone isolated from Embelia ribes

The first synthesis of the unusual nitrogen-containing 3-alkyl-1,4-benzoquinone, N-(3-carboxylpropyl)-5-amino-2-hydroxy-3-tridecyl-1,4-benzoquinone, isolated from Embelia ribes, is reported. The key steps are a microwave-assisted combined Mitsunobu reaction-Claisen rearrangement to introduce the alkyl side chain into 2,5-dimethoxyphenol, followed by alkene reduction, oxidation to the quinone, and sequential displacement of the methoxy groups with hydroxide and GABA tert-butyl ester. Two other naturally occurring benzoquinones, O-methylrapanone and rapanone, were also prepared en route.     

Synthesis of analogues of (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate, an isoprenoid precursor and human gamma delta T cell activator

(E)-1-Hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP) is an intermediate in the non-mevalonate pathway for the biosynthesis of isoprenoids and also serves as a very strong activator of human gamma delta T cells expressing Vgamma9Vdelta2 receptors. This paper describes the synthesis of analogues of HMBPP, in which the diphosphate group is replaced by potential isosteric moieties, i.e., carbamate, N-acyl-N'-oxy sulfamate, or aminosulfonyl carbamate functionalities. The potential of the synthesized analogues to stimulate Vgamma9/Vdelta2 T cell response or to inhibit GcpE and LytB, the last enzymes in the non-mevalonate pathway, was assessed.     

A new CoII complex of diniconazole: synthesis,crystal structure and antifungal activity

A new Co^II complex of diniconazole, namely diaqua[(E)‐(RS)‐1‐(2,4‐dichlorophenyl)‐4,4‐dimethyl‐2‐(1H‐1,2,4‐triazol‐1‐yl‐κN⁴)pent‐1‐en‐3‐ol]cobalt(II) dinitrate dihydrate, [Co(C₁₅H₁₇Cl₂N₃O)₃(H₂O)₂](NO₃)₂·2H₂O, was synthesized and characterized by elemental analysis, IR spectroscopy and single‐crystal X‐ray diffraction. Crystal structural analysis shows that the centrosymmetric Co^II cation is coordinated by four diniconazole ligands and two water molecules, forming a six‐coordinated octahedral structure. There are also two free nitrate counter‐anions and two additional solvent water molecules in the structure. Intermolecular O—H...O hydrogen bonds link the complex cations into a one‐dimensional chain. In addition, the antifungal activity of the complex against Botryosphaeria ribis, Gibberella nicotiancola, Botryosphaeria berengriana and Alternariasolani was studied. The results indicate that the complex shows a higher antifungal activity for Botryosphaeria ribis and Botryosphaeria berengriana than diniconazole, but a lower antifungal activity for Gibberella nicotiancola and Alternariasolani.     

Latonduines A and B,new alkaloids isolated from the marine sponge Stylissa carteri: structure elucidation,synthesis, and biogenetic implications

[structure: see text] Latonduines A (6) and B (7), two new alkaloids with unprecedented heterocyclic skeletons, have been isolated from the Indonesian marine sponge Stylissa carteri. The structures of the latonduines were elucidated by analysis of spectroscopic data and confirmed by the total synthesis of latonduine A (6). It is proposed that ornithine is the biogenetic precursor to the aminopyrimidine fragment of the latonduines.     

Facile synthesis,crystal structure and antifungal activity of dimethylated trifluoroatrolactamide derivatives

Research on Chemical Intermediates - A series of novel substituted 3,3,3-trifluoro-2-methoxy-N-methyl-N,2-diphenylpropanamides were synthesized from α-hydroxyacetamide using CH3I as the...     

Synthesis and structure elucidation of oxidative coupling products of 2-hydroxy-1,4-naphthoquinones

2,3-Dihydro-3-O-(1,4-naphthoquinon-2-yl)-2-oxo-1,4-naphthoquinones are the products of oxidative coupling of substituted 2-hydroxy-1,4-naphthoquinones (regardless of the presence of peri-hydroxy groups in their structures) under the action of lead dioxide. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 294—298, February, 2006.     

First synthesis of the antifungal oidiolactone C from trans-communic acid: cytotoxic and antimicrobial activity in podolactone-related compounds

The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was carried out with an overall yield of 11.7%. The key step in the process consists of a new bislactonization reaction catalyzed by Pd(II), which gives rise to the podolactone-type tetracyclic skeleton from a norlabdadienedioic acid. We also carried out a study of the structure-biological activity of different natural podolactones and their synthetic precursors. Thus, the highest cytotoxic activity was found in dienic dilactones with ether-type substitutions on C-17, whereas the closure of the gamma-lactone ring is not critical for presenting a maximal antimicrobial activity.     

Structure and synthesis of a newly discovered terpenoid isolated from Lavandin oil: Trans-5-hydroxy-2-isopropenyl-5-methylhex-3-enyl acetate

A newly discovered component of the oil of Lavandin abrialis has been shown by spectroscopic data to be trans-5-hydroxy-2-isopropenyl-5-methylhex-3-enyl acetate (I). A synthesis of this material is described.     

Synthesis, structure, and properties of piperidinium 3-(4-chlorophenyl)-2-cyano-3-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)thiopropionimidate

Condensation of 4-chlorobenzaldehyde with cyanothioacetamide and dimedone in the presence of piperidine afforded piperidinium 3-(4-chlorophenyl)-2-cyano-3-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)thiopropionimidate. This salt was studied by X-ray diffraction analysis and used in the synthesis of the previously unknown partially hydrogenated 2-alkylthioquinolin-2-ones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 733–737, April, 2000.     

Stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine from d-mannitol

A novel stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine was achieved from d-mannitol involving the highly stereoselective addition of phenyl Grignard to an allyl imine (de >98%) and ring-closing metathesis (RCM) in the key steps.     

Design,synthesis, and biological activity studies of a new class of sulfonated aurones: First synthesis of acidoaurone isolated from Phyllanthus acidus

A novel series of aurones were designed by introducing sulfonic acid group on ring-A and ring-B of known natural aurones such as hispidol, sulfuretin, maritimetin, and aureusidin. These sulfonated aurones were synthesized by a unique approach. Sulfonation on ring-A or ring-B converts water-insoluble aurones into highly water-soluble aurones. The sulfonated aurones were tested for their antioxidant, antiinflammatory, and AChE inhibition activities along with their natural aurones. Ring-A sulfonated aurones displayed higher antioxidant activity, 5-LOX, and AChE inhibition in comparison with their corresponding natural aurones. Ring-B sulfonated aurones exhibited potent 5-LOX inhibitory activity and significant antioxidant activity. Acidoaurone, a first sulfonated aurone isolated from Phyllanthus acidus was synthesized for the first time and was well characterized using NMR, LC–MS, and further confirmed by HMBC.