Total Synthesis and Structural Revision of the Antibiotic Tetrapeptide GE81112A

The total synthesis of the naturally occurring antibiotic GE81112A, a densely functionalized tetrapeptide, is reported. Comparison of spectral data with those of the natural product and the lack of biological activity of the synthesized compound led us to revise the published configuration of the 3‐hydroxypipecolic acid moiety. This hypothesis was fully validated by the synthesis of the corresponding epimer.     

Unguiculins A-C: cytotoxic bis-guanidine alkaloids from the French Polynesian sponge,Monanchora n. sp

Two new acyclic bis-guanidine alkaloids, unguiculins B-C (2–3), were isolated from a French Polynesian sponge Monanchora n. sp. together with the known compound unguiculin A (1). Their structures were established by spectroscopic data interpretation and comparison with the literature. Unguiculins A-C displayed antiproliferative and cytotoxic efficacy against several human cancer cells with IC₅₀ values in the micromolar range.     

Structural characterization of a lariat ether based on 4,10-diaza-2,3,11,12-dibenzo-18-crown-6 and of a coordination Pb(II) complex using picrate as co-ligand

A new lariat ether, N,N′-di(methylenecarboxyethoxy)-4,10-diaza-2,3,11,12-dibenzo-18-crown-6, C₂₈H₃₈N₂O₈, has been characterized and tested for Pb²⁺ extraction in a picrate medium. The isolated complex, [(picrato-O,O′)-(N,N′-di-methylenecarboxyethoxy-4,10-diaza-2,3,11,12-dibenzo-18-crown-6)]-lead(II) picrate, [C₃₄H₄₀N₅O₁₅Pb]⁺[C₆H₂N₃O₇]⁻, includes a 7-coordinated Pb²⁺ cation complex where sidearms of the macrocycle are involved in complexation, with Pb‐O bond lengths of 2.587(4) and 2.617(4) ?. Picrate ions serve both as co-ligand and as anion for charge balance. Both free ligand and Pb²⁺ complex have been X-ray characterized: a = 18.4723(16), b = 24.0057(19), c = 14.4309(14) ?, β = 112.962(7)°, P2₁/c, for the ligand; a = 12.7591(15), b = 21.951(2), c = 16.4389(15) ?, β = 97.144(8)°, P2₁/n, for the complex.     

The molecular structure of 3(5)-methyl-4,5(3)-trimethylenepyrazole hydrochloride and its13C and15N NMR spectroscopy

The title compound (C₇N₂H₁₀, HC1, 1/2H₂O) crystallizes in the space groupC2/c with cell parameters:a=11.651(9),b=16.309(1),c=9.167(1)Å,=94.95(3)°,Z=8, withd=1.287 g cm^–3. One of the chlorine atoms lies on a twofold axis, the second and the oxygen atom of the water molecule have disordered positions. Intermolecular interactions through hydrogen bonds are established between nitrogen atoms of the pyrazole ring and chlorine atoms or the water molecule. In this way, chains of molecules are built; these chains, through van der Waals interactions, form layers which are stacked in the a direction. The¹H,¹³C, and¹⁵N NMR (this last using the double labelled compound) have been recorded in solution and the¹³C NMR spectrum also in the solid state (CP/MAS technique). The NMR parameters ( andJ's) thus obtained are discussed using the molecular structure.     

Anti-Markovnikov hydroarylation of styrenes catalyzed by an in situ generated ruthenium complex

An efficient and practical catalytic system for the anti-Markovnikov ruthenium-catalyzed hydroarylation of styrenes with acetophenone, allowing a straightforward access to bibenzyl backbones, is described for the first time: this process, involving regioselective C-H bond activation, is complementary to a Friedel-Crafts type reaction giving the branched adduct.     

Recent synthetic approaches toward non-anomeric spiroketals in natural products

Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.     

Efficient and simple synthesis of 6-aryl-1,4-dimethyl-9H-carbazoles

A synthetic method for the preparation of 6-aryl-1,4-dimethyl-9H-carbazoles involving a palladium catalyzed coupling reaction of 1,4-dimethyl-9H-carbazole-6-boronic acids and (hetero)aryl halides is described.     

Synthesis and testing of chromogenic phenoxazinone substrates for beta-alanyl aminopeptidase

Novel 7-N-(beta-alanyl)aminophenoxazin-3-one salts 27a-d have been synthesized and tested as chromogenic substrates for beta-alanyl aminopeptidase, which is present in Pseudomonas aeruginosa, the most common respiratory pathogen in patients with cystic fibrosis. The biological results show that 7-N-(beta-alanyl)amino-1-pentylphenoxazin-3-one trifluoroacetate salt 27a is a chromogenic substrate for this bacterium, with a low degree of diffusion in nutrient media for growing bacterial cultures and a bright red colour, making it easily distinguishable from the agar background.     

Sterically hindered benzophenones via rhodium-catalyzed oxidative arylation of aldehydes

Efficient cross-coupling, allowing a straightforward access to congested benzophenones, between aromatic aldehydes and potassium aryltrifluoroborates, is described in the presence of a rhodium/tri-tert-butylphosphane catalyst system and acetone as cosolvent. The use of the stable phosphonium salts of tri-tert-butylphosphane prevented the use of highly oxidizable tri-tert-butylphosphane and allowed a careful control of the stoichiometry with the rhodium.     

Homophymine A, an anti-HIV cyclodepsipeptide from the sponge Homophymia sp

A new anti-HIV cyclodepsipeptide, homophymine A, was isolated from a New Caledonian collection of the marine sponge Homophymia sp. The structure of homophymine A was determined by interpretation of spectroscopic data, acid hydrolysis, and LC-MS analysis. Homophymine A contains 11 amino acid residues and an amide-linked 3-hydroxy-2,4,6-trimethyloctanoic acid moiety. Along with four D-, two L-, and one N-methyl amino acids, it also contains four unusual amino acid residues: (2S,3S,4R)-3,4-diMe-Gln, (2R,3R,4S)-4-amino-2,3-dihydroxy-1,7-heptandioic acid, L-ThrOMe, and (2R,3R,4R)-2-amino-3-hydroxy-4,5-dimethylhexanoic acid. In a cell-based XTT assay, homophymine A exhibited cytoprotective activity against HIV-1 infection with a IC50 of 75 nM.