Hupermine A,a novel C16N2-type Lycopodium alkaloid from Huperzia phlegmaria

A novel C₁₆N₂-type Lycopodium alkaloid consisting of a quinolizidine with a 6-dimethylaminohexyl side chain, hupermine A (1), was isolated from the club moss of Huperzia phlegmaria, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Kingamide A, a new indole alkaloid from the ascidian Leptoclinides kingi

Chemical investigation of the CH₂Cl₂/MeOH extract from the Australian ascidian Leptoclinideskingi led to the isolation of a new brominated indole alkaloid, kingamide A (1). The planar structure of kingamide A was elucidated following the interpretation of 1D/2D NMR and MS data, and the absolute configuration was determined using Marfey’s method. This is the first report of a natural product from L. kingi.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

A convergent and stereoselective synthesis of a seco-precursor of macrolactin A

A seco-precursor of macrolactin A was synthesized by coupling two advanced segments. Wittig reaction and Horner-Emmons reaction were utilized to construct the three characteristic E,Z and E,E dienes. The C₁-C₁₀ segment was synthesized through Horner-Emmons reaction with phosphonate reagent. The α-alkylation of sulfone stabilized anion with allyl bromide followed by desulfonation gave the C₁₁-C₂₄ segment.     

A cyclic trimer of 2-(2-aminophenoxy)propionic acid with a bowl-shaped structure

A cyclic trimer of (R)-2-(2-aminophenoxy)propanoic acid, a δ-amino acid analogue, was synthesized. Molecular mechanics calculations on the cyclic trimer predicted that a concave network of sequential hydrogen bonds forms a C₃-symmetric bowl-shaped structure. Evidence for this conformation was found in the NMR spectra of the trimer in d-chloroform. Although the single-crystal structure of the cyclic trimer indicates that chloroform could be included in the bowl-shaped structure, the conformation was not C₃-symmetric and the hydrogen bonding network was of a different mode. These different conformations between solid and solution were reasonably clear from IR spectra.     

Synthesis and characterization of a tetraruthenium butterfly cluster containing a quadruply-bridging ligand derived from an N,N′-dipyrid-2-ylurea

The tetraruthenium cluster complex [Ru₄(μ₄-κ⁴-dmpu)(CO)₁₀], H₂dmpu = N,N′-bis(6-methylpyrid-2-yl)urea, has been prepared by treating [Ru₃(CO)₁₂] with H₂dmpu in toluene at reflux temperature. An X-ray diffraction study has determined that this cluster has a butterfly metallic skeleton hold up by a doubly-deprotonated N,N′-bis(6-methylpyrid-2-yl)urea ligand (dmpu). This ligand has the pyridine N atoms attached to the wing-tip Ru atoms and the amido N atoms spanning Ru-Ru wing-edges, in such a way that the cluster has C₂ symmetry. The donor atoms of doubly-deprotonated N,N′-dipyrid-2-ylureas seem to be appropriately arranged to hold butterfly tetranuclear clusters.     

Synthesis and structural characterization of a zinc(II) complex of the mycobactericidal drug isoniazid - Toxicity against Artemia salina

A new zinc(II) complex of the mycobactericidal drug isoniazid (complex 1) was synthesized and characterized by XRD, vibrational spectroscopy (IR, Raman) and thermogravimetric analysis. The complex is constituted by two isoniazid (INH) molecules, six hydration water molecules and two perchlorate counter-ions for each metal center (C₁₂H₂₆N₆Cl₂O₁₆Zn). Zinc(II) adopts a distorted octahedral geometry, where two INH molecules coordinate in a bidentate manner through the hydrazide group (N, O) and the other two isoniazid residues complete the coordination sphere of zinc(II) through their aromatic nitrogen atoms. This coordination pattern gives rise to a 2-D coordination polymer. Complex 1 belongs to the monoclinic system [a = 8.1190(2) Å, b = 17.977(4) Å, c = 9.1051(2) Å and β = 100.87(3)°], space group P2₁. A biological assay with Artemia salina was also performed. Complex 1 is almost 8.5 times more active than the free ligand. Its toxicity against A. salina correlates well with the cytotoxic activity for some human solid tumors. Therefore, antitumoral properties could be expected from complex 1.     

Total synthesis of cucurbitoside A using a novel fluorous protecting group

The first total synthesis of cucurbitoside A was achieved using a new fluorous N-phenylcarbamoyl (^FCar) protecting group. The ^FCar group was introduced into carbohydrates in high yield and was selectively removed with Bu₄NNO₂ without damaging other acyl protecting groups. The synthetic intermediates were easily isolated by fluorous solid-phase extraction.     

A picolinate-N2 complex of rhenium, the first dinitrogen complex bearing a carboxylate or a N,O-ligand

A new dinitrogen rhenium(I) complex with a picolinate ligand has been prepared and fully characterized, providing the first example of a genuine NN complex bearing a carboxylate or a N,O-coligand. The Lever electrochemical E_L ligand parameter was estimated for the first time for the picolinate ligand and shows that its carboxylate arm has a net electron-donor character similar to that of chloride, thus stabilizing the trans Re-N₂ bond.     

Aerobic alcohol oxidation using a PdCl2/N,N-dimethylacetamide catalyst system under mild conditions

A new and simple PdCl₂/DMA catalytic system for the alcohol oxidation has been developed using molecular oxygen as the sole oxidant under mild conditions. The catalytic system could be reused for three runs without significant loss of catalytic activity. A variety of active and non-active alcohols were oxidized to their corresponding carbonyl compounds in good to excellent yields. Gas-uptake kinetics for the catalytic system was also investigated. The ca. 1:1 molar ratio of O₂ uptake to product yield is observed, suggesting the in situ formation of H₂O₂.     

Titanium superoxide: a heterogeneous catalyst for anti-Markovnikov aminobromination of olefins

A new facile procedure for the aminobromination of olefins in high yields has been described using p-toluene sulfonamide (p-TsNH₂) and N-bromosuccinimide (NBS) as nitrogen and bromine sources, respectively, and titanium superoxide as a truly heterogeneous catalyst. The formation of anti-Markovnikov product exclusively in all the cases studied possibly proceeding through a free radical reaction pathway is remarkable.     

Synthesis of polylactide using a zinc complex containing (S)-N-ethyl-N-phenyl-2-pyrrolidinemethanamine

The reaction between ZnCl₂ and (S)-N-ethyl-N-phenyl-2-pyrrolidinemethanamine (S-EPP) as a chiral ligand affords [ZnCl₂(S-EPP)], whose structure has been determined by X-ray crystallography. [ZnEt₂(S-EPP)] has demonstrated high activity toward the polymerization of rac-lactide with a maximum turnover frequency (TOF) of 121. Despite the intended stereocontrol by employing a chiral ligand, however, the observed heterotacticity was limited to under 0.6. The MWDs of the PLAs were found to be modulated by changing the solvent or controlling the concentration of the monomer in the solution. The glass transition temperature (T_g) was critically dependent on the MW within the narrow MWD regime, but the dependence became significantly shallow when the MWD was broadened.     

Chemoenzymatic synthesis of a focused library of enantiopure structured 1-O-alkyl-2,3-diacyl-sn-glycerol type ether lipids

A highly efficient two-step chemoenzymatic synthesis of enantiopure structured ether lipids of the 1-O-alkyl-2,3-diacyl-sn-glycerol type has been developed. Chimyl, batyl and selachyl alcohols possessing pure saturated fatty acid (SFA) attached to the sn-3 position and pure EPA and DHA attached to the sn-2 position were obtained under full regiocontrol. This was offered by mild conditions and a highly efficient lipase that operated at room temperature. High-resolution ¹H NMR spectroscopy was used to monitor the progress of the reactions and to evaluate the full regiocontrol of the reactions involved by keeping track of all prospective adducts involved in these reactions. This was extended to preparation of a focused library of eight monoacyl intermediate adducts for all even-numbered SFA ranging from C₂-C₁₆ and the corresponding EPA and DHA structured diacyl glycerol ethers (DAGE) products for chimyl, batyl and selachyl alcohols, the total of 72 compounds.     

Approach to highly functionalized oxazolones by a Pd-catalyzed cyclization of N-alkynyl tert-butyloxycarbamates

A mild and operationally simple approach to highly functionalized oxazolones has been developed, which involves an intramolecular oxypalladation of N-alkynyl tert-butyloxycarbamates, followed by either protonolysis of the alkenyl C-Pd bond to afford 3,5-disubstituted oxazolones or allylation with allyl halides in the presence of Ag₂CO₃ to generate 3,4,5-trisubstituted oxazolones, respectively.     

Regioselective cleavage of the bis-benzylidene acetal of d-mannitol under oxidative and reductive conditions: a new approach to C2-symmetric chiral ligands

A highly regioselective oxidative cleavage of 1,3:4,6-di-O-benzylidene-d-mannitol was carried out using NBS and the resultant product was readily converted to the C₂-symmetric chiral ligand, (R,R)-3,4-dihydroxy-1,5-hexadiene. On the other hand, reductive cleavage of 1,3:4,6-di-O-benzylidene-d-mannitol was achieved in a highly regioselective manner using BF₃·OEt₂ and Et₃SiH to give a highly functionalized benzyl ether, which was converted to a synthetically useful C₂-symmetric bis-amino alcohol derivative.     

Synthesis of indoles with a polyfluorinated benzene ring

A two-step sequence consisting of a Sonogashira coupling of polyfluorinated 2-iodoanilines with terminal alkynes, followed by a KOH promoted cyclization of the 2-alkynylanilines thus formed, has been developed as a one-pot synthesis of 2-R-indoles (R=n-Bu, Ph, CH₂OTHP→CH₂OH, C(CH₃)₂OH→H) containing a polyfluorinated benzene moiety.     

Saccharonol B,a new cytotoxic methylated isocoumarin from Saccharomonospora azurea

From an antimicrobial gram-positive actinomycete strain of Saccharomonospora azurea (MTCC11714) isolated from high altitude soil of Kargil (J&K, India), a new isocoumarin saccharonol B (2) along with two known compounds viz. saccharonol A (1) and piericidin A₃ (3) was isolated and characterized. The structure of the new compound was established based on extensive 2D-NMR data. Saccharonol B (2) exhibited mild antimicrobial activity against a standard panel of microorganisms Staphylococcus aureus ATCC 29213, Candida albicans ATCC 90028, and Aspergillus fumigatus MTCC 1811 with MIC values in the range of 128–248 μg/mL. Saccharonol B (2) and piericidin A₃ (3) showed selective cytotoxic activity against human pancreatic carcinoma cell line (MIAPaCa-2) with IC₅₀ values of 9 and 8 μM, respectively. Mechanistic studies indicated that saccharonol B (2) arrests S-phase of the cell cycle and causes dose-dependent loss of mitochondrial potential in MIAPaCa-2 cells.     

Amphezonol A, a novel polyhydroxyl metabolite from marine dinoflagellate Amphidinium sp.

Amphezonol A (1), a novel polyhydroxyl linear carbon-chain metabolite, has been isolated from the cultured marine dinoflagellate Amphidinium sp., which was isolated from an Okinawan marine acoel flatworm Amphiscolops sp. The structure of 1 was elucidated by detailed analyses of 2D NMR spectra. Amphezonol A (1) possesses one tetrahydrofuran ring, two tetrahydropyran rings, and twenty-one hydroxyl groups on C₆₀-linear aliphatic chain with one exo-methylene and one methyl branch. Amphezonol A (1) exhibited a modest inhibitory activity against DNA polymerase α.     

Highly enantioselective hydrogenation of exocyclic double bond of N-tosyloxazolidinones catalyzed by a neutral rhodium complex and its synthetic applications

A highly enantioselective synthesis of optically active N-tosyl-4-alkyl-1,3-oxazolidin-2-ones based on the asymmetric hydrogenation of the trisubstituted exocyclic double bond of N-tosyl-4-alkylidene-1,3-oxazolidin-2-ones under the catalysis of neutral [Rh(COD)Cl]₂ (COD=1,5-cyclooctadiene) and (S)-(+)-DTBM-SEGPHOS was developed. The utility of this highly enantioselective reaction was exemplified by the synthesis of optically active amino acids, amino alcohols, and piperidine derivatives.