A new protecting group ‘3,5-O-sulfinyl’ for xylo-nucleosides. A simple and efficient synthesis of 3-amino-3-deoxyadenosine (a puromycin intermediate), 2,2-anhydro-pyrimidine nucleosides and 2,3-anhydro-adenosine

We developed a new protecting group, the cyclic sulfite for the protection of the 3^′,5^′-dihydroxy group of nucleosides. Seven cyclic sulfites, 4a-c, 5a-b, and 6a-b were prepared in high yields from the corresponding xylo-uridines 1 and 2, and xylo-adenosines 3 with thionyl chloride, respectively. Synthesis of the puromycin intermediate 8 was carried out by deprotection of the sulfite moiety through an intramolecular cyclization of the 2^′-α-carbamate 7.     

Laccase-catalyzed conversion of green tea catechins in the presence of gallic acid to epitheaflagallin and epitheaflagallin 3-O-gallate

Green tea extract containing catechin mixtures was treated with gallic acid using laccase (EC 1.10.3.2) to improve its function as a food material. After enzymatic oxidation, two new products were detected on an HPLC chromatogram. These products were purified by extraction with ethyl acetate, sequential column chromatographies, and crystallization. On the basis of ¹H/¹³C NMR, MALDI-TOF/high resolution MS, and UV-visible absorption spectral analyses, they were confirmed to be epitheaflagallin (5) and epitheaflagallin 3-O-gallate (6). This enzymatic process allows us to preferentially convert catechin derivatives in a crude mixture of green tea into different compounds.     

Phosphoramidite building blocks for efficient incorporation of 2′-O-aminoethoxy(and propoxy)methyl nucleosides into oligonucleotides

A simple and efficient method for the preparation of eight phosphoramidite building blocks for incorporation of 2′-O-(2-aminoethoxymethyl)ribonucleosides and 2′-O-(3-aminopropoxymethyl)ribonucleosides into synthetic oligonucleotides has been developed. The synthetic routes are maximally convergent and provide sufficient amounts of phosphoramidites for several solid-phase synthesis coupling reactions. Using acyclic derivatives 17a,b the overall yields of phosphoramidites 2 and 3 were increased up to 50% for pyrimidine nucleosides and up to 30% for purine derivatives with substantial decrease of total reaction steps. The 2′-O-substituent was found to be stable during oligonucleotide synthesis. The resulting oligonucleotides are of particular interest for post-synthetic functionalization and conjugation.     

Production and degradation mechanism of theacitrin C, a black tea pigment derived from epigallocatechin-3-O-gallate via a bicyclo[3.2.1]octane-type intermediate

Black tea is rich in polyphenols and has been shown to have various health benefits; however, its components have not yet been clarified in detail. Enzymatic oxidation of epigallocatechin-3-O-gallate, the most abundant polyphenol in tea, is thought to contribute significantly to the production of black tea polyphenols. We identified theacitrin C, an unstable black tea pigment, as an enzymatic oxidation product of epigallocatechin-3-O-gallate. Degradation of theacitrin C afforded theacitrinin A and 2,3,5,7-tetrahydroxychroman-3-O-gallate. Furthermore, theacitrinin B, which was isolated from black tea, is deduced to be a degradation product of theacitrin A, the desgalloyl analogue of theacitrin C. The structures of theacitrinins A and B were elucidated based on spectroscopic data. This is the first time that a degradation product of theacitrin has been isolated from black tea. We also examined the influence of esterification of the epigallocatechin C-3 hydroxyl group on the decomposition of bicyclo[3.2.1]octane-type intermediates.     

Efficient synthesis of 5′-O(N)-carbamyl and -polycarbamyl nucleosides

A simple and efficient method for the preparation of 5′-O(N)-carbamyl and 5′-O(N)-polycarbamyl nucleoside derivatives is reported. The method consisted of treatment of 2′,3′-O-protected purine (Ado, Ino) or pyrimidine nucleosides (Thd, Urd) with trichloroacetylisocyanate, followed by cleavage of the trichloroacetyl moiety by silica-gel promoted methanolysis during column chromatography. Iterative application of this method gave mono, di, and tricarbamyl derivatives in good to excellent yields (ave = 80%).     

Straightforward synthesis of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes via 2′,3′-O-orthoester group elimination: a simple route to 3′,4′-didehydronucleosides

Straightforward, high-yielding syntheses of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes and 3′-deoxy-3′,4′-didehydronucleosides starting from 2′,3′-O-orthoester derivatives of ribonucleosides are described.     

A single chalcone and additional rotenoids from Lonchocarpus nicou

The lipophile extract of Lonchocarpusnicou roots afforded the new pyranochalcone 3-O-methylabyssinone A as well as the new rotenoids 7′-hydroxytephrosin, and 7′-nor-6′-oxo-2′,3′-dehydrorotenone, both compounds occurring with the known 7′-hydroxydeguelin and 7′-nor-6′-oxo-2′,3′-dehydro-12aβ-hydroxyrotenone. Furthermore, two rotenoid epoxides previously reported as resulting from the direct oxidative conversion of rotenone and 12aβ-hydroxyrotenone, respectively, were isolated for the first time from a plant source. All the structures were established on the basis of UV, MS, and NMR data.     

Improved synthesis of N-alkyl substituted dithieno[3,2-b:2′,3′-d]pyrroles

A new, convergent and improved synthetic method to prepare N-alkyl substituted dithienopyrroles is described. The procedure consists of a Pd-catalyzed amination of 3,3′-dibromo-2,2′-bithiophene. The reaction conditions were optimized, which makes this method applicable to prepare these molecules easily in high yields and on a large scale.     

Synthesis of pelargonidin 3-O-6″-O-acetyl-β-d-glucopyranoside, an acylated anthocyanin, via the corresponding kaempferol glucoside

The first total synthesis of pelargonidin 3-O-6″-O-acetyl-β-d-glucopyranoside, an acylated anthocyanin of magenta-colored Verbena flowers, was successfully carried out. The key intermediate, protected kaemferol 3-O-glucoside, was constructed by the Baker-Venkataraman rearrangement from a glucosyloxyacetophenone followed by Zn-Hg reduction to the corresponding acylated anthocyanin.     

Grignard reagent-promoted 6-endo-dig cyclization: instantaneous synthesis of original dipyrido[1,2-a:3′,4′-d]imidazole

Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2-a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.     

Preparation of 6-chloropyrazolo[3,4-b]pyridine-5-carbaldehydes by Vilsmeier-Haack reaction and its use in the synthesis of heterocyclic chalcones and dipyrazolopyridines

Novel 6-chloropyrazolo[3,4-b]pyridine-5-carbaldehydes 5 have been synthesized from the 4,5-dihydropyrazolo[3,4-b]pyridine-6-ones 4 via Vilsmeier-Haack reaction. Further treatment of carbaldehydes 5 with acetophenones 6 and hydrazine hydrate afforded chalcone analogues 7 and dipyrazolo[3,4-b:4′,3′-e]pyridines 8, respectively.     

Convenient synthesis of N-isobutyryl-2′-O-methyl guanosine by efficient alkylation of O-trimethylsilylethyl-3′,5′-di-tert-butylsilanediyl guanosine

We present a novel route for the synthesis of N²-isobutyryl-2′-O-methyl guanosine, introducing 3′,5′-di-tert-butylsilyl and O⁶-trimethylsilylethyl groups as efficient protections during the 2′-O-methylation step with NaH/CH₃I. These protections were then removed simultaneously in a single step with TBAF. The eight-step synthesis is easy to perform, employing convenient commercially available reagents; crude mixtures are of satisfying purity, so only three chromatography purifications were required. Title compound was obtained in 25% overall yield from guanosine.     

Facile synthesis of regio-isomeric naphthofurans and benzodifurans

Naphtho[1,2-b]furans 1a-f, naphtho[2,1-b]furans 2a-f, benzo[1,2-b:5,4-b′]difurans 3a-b, benzo[1,2-b:4,5-b′]difurans 4a-b, and benzo[1,2-b:4,3-b′]difurans 5a-b were synthesized by base-catalyzed cyclization reaction of the corresponding o-alkoxybenzoylarene derivatives. The o-alkoxybenzoylarenes were obtained from the etherification reaction of the o-hydroxybenzoylarenes, which were prepared either by the reaction of methoxyarenes with benzoyl chloride in the presence of aluminum chloride or by photo-Fries rearrangement of aryl benzoates.     

A concise synthesis of 4′-O-methyl honokiol

A concise and protecting group free synthesis of the naturally occurring neolignan 4′-O-methyl honokiol is developed. The key biaryl bond is constructed by 1,2-addition of an aryl Grignard reagent to a dienone followed by rearrangement.     

A new synthesis of key intermediates for the assembly of polycyclic ethers: Yb(OTf)3-promoted formation of O,S-acetals from α-fluorosulfides and alcohols

We report a new reaction for the direct construction of O,S-acetals, key intermediates in the assembly of fused polycyclic ethers. α-Fluorosulfides and secondary alcohols were coupled by the action of Yb(OTf)₃ to generate O,S-acetals in high yield. The neutral and selective nature of the reaction should be useful for synthesizing natural and artificial polyethers with multisensitive functionalities.     

Cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines): synthesis, structure and mechanism of their formation

Reactions of 3-alkylamino-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones with cyclohexyl- and cycloheptylamines in the presence of AgPy₂MnO₄ produce novel cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines). Detailed information concerning the scope and mechanism of these transformations is discussed.     

Selective palladium-catalyzed amination of the heterocyclic core of variolins

A new and selective palladium-catalyzed amination of the pyrido[3′,3′:4,5]pyrrolo[1,2-c]pyrimidine nucleus, the heterocyclic core of the variolin alkaloids, is described. The method allows the introduction of amino and aryl- and alkylamino substituents on the C9 position in advanced precursors of variolin B and deoxyvariolin.     

A novel acylated quercetin tetraglycoside from oolong tea (Camelia sinensis) extracts

A novel acylated quercetin tetraglycoside, namely quercetin 3-O-(2^G-p-coumaroyl-3^G-O-β-l-arabinosyl-3^R-O-β-d-glucosylrutinoside) was isolated from oolong tea (Camelia sinensis) extracts. Structural analysis of this compound was achieved by NMR, TOF-MS and high-resolution FAB-MS. Triglycosyl flavonols have previously been reported from tea leaves and tea seeds however this is the first report of an aromatic acylated and tetraglycosyl flavonol.     

Synthetic studies of carzinophilin. Part 3: Synthetic approach toward carzinophilin and successful synthesis of 13-O-desacetyl-12,13-di-O-benzyl-4-O-methylcarzinophilin

The synthetic procedures of the title compound (2), a protected form of carzinophilin (1), were developed. While efforts toward the total synthesis of 1 failed, comparison of the ¹H NMR spectra of 2 and some other related compounds with that of 1 provided definite support for the absolute stereochemistry of 1 which has a complicated history regarding its structure.     

Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines as synthons for the preparation of polycondensed heterocycles: reaction with chlorocarboxylic acid chlorides

Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines and 2-amino[1,2,4]triazolo[5,1-b]quinazolines react with the chlorides of chloroacetic, 3-chloropropanoic, and 4-chlorobutanoic acids at 0–5 °C to give amides through acylation of the 2-amino group. Heating the corresponding 3-chloropropanoyl derivatives at 80–90 °C in DMF leads to selective intramolecular alkylation at N-3 to form the chlorides of partially hydrogenated [1,2,4]triazolo[1,5-a:4,3-a′]dipyrimidin-5-ones and pyrimido[2′,1′:3,4][1,2,4]triazolo[5,1-b]quinazolin-12-ones. It may be more convenient to prepare such compounds through one-pot processes. Some reactions of the synthesized chlorides of polycondensed heterocycles have been studied. Conditions have been found to effect the selective synthesis of free bases, oxidative aromatization or hydrolysis of the dihydropyrimidine cycle, and the selective hydrolytic cleavage or elimination of the pyrimidone ring. Some of the resulting compounds represent new mesoionic heterocycles.