ABSTRACT
The synthesis of a spirolactone analogue of xylapyrraside B1, a potent antioxidant agent, is described. The key step is the stereoselective formation of the spirolactone skeleton via the formal [3+2] annulation of the isopropylidene-protected glyceraldehyde and δ-methylene lactone, mediated by trifluoroborane etherate. This study addresses the stereoselective synthesis of pyrrolomorpholine spiroketal alkaloids, enabling the production of these bioactive compounds and their analogues.
ABSTRACT
A highly regioselective method was developed for the preparation of pyridazine derivatives via the aza-Diels-Alder reaction of 1,2,3-triazines with 1-propynylamines under neutral conditions. This methodology allowed direct access to a wide range of 6-aryl-pyridazin-3-amines in high yields with good functional group compatibility. Key features of this strategy included a broad substrate scope and simple, metal-free, and neutral reaction conditions.
ABSTRACT
An efficient approach to stereoselective construction of a spiro-γ-lactone core structure via BF3-promoted formal [3 + 2] annulation of aldehydo-aldose derivatives with γ-methylene-γ-butyrolactone has been developed. The spiro-γ-lactone derivative was then used in an efficient total synthesis of (+)-pyrenolide D. The developed chemistry paves the way for total synthesis of structurally diverse natural products containing spiro-lactone cores.
ABSTRACT
A highly efficient and convenient method for the synthesis of 6-aryl-1,2,3-triazine-4-carboxylate esters has been developed using readily accessible ( Z)-4-aryl-2,4-diazido-2-alkenoates. This reaction is performed under mildly basic conditions without the assistance of any transition metals or strong acid.
ABSTRACT
6-Thioguanine (1a) is considered to be photochemotherapeutic due to its specific characteristics of photosensitivity to UVA light and singlet molecular oxygen generation. To extend its phototherapeutic ability, two related thioguanines, 8-thioguanine (2a) and 6,8-dithioguanine (3a), have been designed and explored. Since the solubility of these thioguanines in dehydrated organic solvents is too poor to study, their triacetyl-protected ribonucleosides, that is, 2',3',5'-tri-O-acetyl-6-thioguanosine (1c), 2',3',5'-tri-O-acetyl-8-thioguanosine (2c) and 2',3',5'-tri-O-acetyl-6,8-dithioguanosine (3c) were prepared and investigated. The absorption maxima of 1c, 2c and 3c in acetonitrile were found at longer wavelengths than that of unthiolated guanosine (4c). Especially, 3c has the longest wavelength for absorption maximum and the highest value in terms of molar absorption coefficient among all thionucleobases and thionucleosides reported. These absorption properties were also well reproduced by quantum chemical calculations. Quantum yields of singlet oxygen generation of 2c and 3c were determined by near-infrared emission measurements to be as large as that of 1c. These results suggest that the newly synthesized thioguanosines, in particular 3c, can be further developed as a potential photosensitive agent for light-induced therapies.
Subject(s)
Guanosine/analogs & derivatives , Quantum Theory , Singlet Oxygen/chemistry , Thionucleosides/chemistry , Carbon-13 Magnetic Resonance Spectroscopy , Guanosine/chemical synthesis , Guanosine/chemistry , Photochemical Processes , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Spectrophotometry, Ultraviolet , Spectroscopy, Near-Infrared , Thionucleosides/chemical synthesisABSTRACT
2',3',5'-Tri- O-acetyl-6,8-dithioguanosine (taDTGuo) is a nucleoside derivative of drug 6-thioguanine and under further development as a potential photochemotherapeutic agent due to its desirable properties of photosensitivity to UVA light and singlet molecular oxygen generation. The photochemical characteristics of taDTGuo under biological conditions (namely in aqueous solution) were intensively investigated by the steady-state absorption and emission, time-resolved near-infrared emission measurements, and quantum chemical calculations. taDTGuo was found to be held in sequential acid dissociation equilibria within pH 3.79-11.93. With the global fitting analysis of the absorption spectra at various pHs, two p Ka values of the equilibria were determined to be 7.02 ± 0.01 and 9.79 ± 0.01. Quantum chemical calculations suggested that its mono- and dianionic species in the ground state should be 1-imide anionic form (N1-taDTGuo-) and 1,7-di-imide anionic form (taDTGuo2-). taDTGuo generates a singlet molecular oxygen effectively and has pH-dependent quantum yields. In conclusion, taDTGuo would be very useful as a potent agent for photochemotherapy under certain carcinomatous pH conditions.
Subject(s)
Guanosine/chemistry , Quantum Theory , Singlet Oxygen/chemistry , Acetylation , Hydrogen-Ion Concentration , Solutions , Water/chemistryABSTRACT
The [3 + 2] annulation of 2,3-O-isopropylidene-aldehydo-aldose with methallyl ether leads to the stereoselective formation of a substituted tetrahydrofuran system, which is converted to a bicyclic lactone derivative via consecutive deprotection, oxidative cleavage of the terminal diol, oxidation of the resulting lactol, and Barton-McCombie deoxygenation. The efficiency of this process was demonstrated by the first total synthesis of Plakortone L.
Subject(s)
Lactones/chemical synthesis , Animals , Australia , Ether , Furans , Lactones/chemistry , Lactones/isolation & purification , Molecular Structure , Oxidation-Reduction , Porifera/chemistry , StereoisomerismABSTRACT
Influence of carbohydrate protecting groups on intramolecular glycosylation was examined, and it was found that the use of 4-methoxybenzyl group as the protection for the 4-O position as well as t-butyldimethylsilyl group at the 3-O position was necessary to obtain desired beta-nucleosides in good yields.
Subject(s)
Nucleosides/chemistry , Nucleosides/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Glycosylation , Pyrimidine Nucleosides/chemistryABSTRACT
In model studies directed to the total synthesis of guanofosfocins, a unique glycosidic bond formation between the 8-oxo-purine nucleosides and mannopyranose derivatives under Mistunobu conditions is described.
Subject(s)
Mannose/chemical synthesis , Purine Nucleosides/chemistry , Glycosylation , Indicators and Reagents , Mannose/analogs & derivatives , Models, Molecular , Molecular Conformation , Streptomyces , TrichodermaABSTRACT
2',6'-Dideoxy-beta-D-hexopyranosyl pyrimidine nucleoside, which is a component of anticoccidal antibiotics--cytosaminomycins, was synthesized in a stereoselective manner via the intramolecular pyrimidine delivery method. Further glycosylaion of the 4'-position with a glycosyl fluoride gave the disaccharide nucleoside skeleton of the cytosaminomycins.