A highly stereocontrolled and efficient synthesis of α- and β-pseudouridines

A five-step practical and stereocontrolled synthesis of α- and β-pseudouridines from d-ribonolactone is described. The key step involves a highly stereoselective reduction of a hemiketal C-nucleoside intermediate in each case. Multi-gram quantities of β-pseudouridine can now be made available.     

Novel epimerization of aromatic C-nucleosides with electron-withdrawing substituents with trifluoroacetic acid-benzenesulfonic acid using mild conditions

Trifluoroacetic acid and benzenesulfonic acid in dichloromethane at ambient temperature have been found to be efficient co-catalysts for the epimerization of C-nucleosides with electron-withdrawing substituents. This approach provides a convenient route to the β anomer of the nucleosides with high yields in the range 54-78%. Synthesis of the 3′-phosphoramidite of 2,4-difluorophenyl C-nucleoside suitable for solid-phase DNA synthesis is described.     

An efficient approach to 2,5-anhydro-glucitol-based 1′-homo-N-nucleoside mimetics

This Letter describes an efficient synthesis of a range of 1′-homo-N-nucleoside mimetics with a series of 4-substituted 1,2,3-triazoles replacing the natural nucleobase. The synthesis of 6-O-monosulfated 1′-homo-N-nucleoside mimetic derivatives is also discussed.     

Design and synthesis of a novel ring-expanded 4′-thio-apio-nucleoside derivatives

The synthesis of a ring-expanded 4′-thio-apio-nucleoside derivative 4, designed to serve as a potential anti-HIV agent, is described. The epoxy alcohol derivative 10, prepared from 2-butene-1,4-diol, was converted to an allylsulfide derivative 13 in 3 steps. Ring-closing-metathesis of 13 gave the dihydrothiopyran derivative 20, which was further converted into sulphoxide 24. A Pummerer-type thioglycosylation reaction of 24 with a persilylated uracil derivative, followed by conversion to a cytosine derivative and deprotection, gave a racemic mixture of the ring-expanded 4′-thio-apio-nucleoside derivative 4 in good yield.     

Total synthesis and structural confirmation of malayamycin A: a novel bicyclic C-nucleoside from Streptomyces malaysiensis

[reaction: see text] The stereocontrolled synthesis of malayamycin A, a novel naturally occurring bicyclic C-nucleoside of the perhydrofuropyran type, is described.     

A new one-pot synthesis of all E-retinoic acid via a new enaminodiester synthon

A ‘one-pot’ synthesis of allE-retinoic acid from a new enaminodiester was described. The enaminodiester was easily produced from methyl isopropylidenemalonate and DMF-DMA.     

Gold(I)-catalyzed [4+2] cycloaddition of N-(hex-5-enynyl) tert-butyloxycarbamates

A study concerning the gold(I)-catalyzed transformation of N-(hex-5-enynyl) tert-butyloxycarbamates is described. The mild conditions employed allow the moderately efficient but stereoselective synthesis of a range of bicyclic carbamates following a formal [4+2] cycloaddition process.     

A novel effective electrophile: β-trifluoroacetylketene diphenyldithioacetal S,S-tetroxide

A synthesis of a novel electrophilic reagent--β-trifluoroacetylketene diphenyldithioacetal S,S-tetroxide 3 is described. The reaction of 3 with various electron-rich aromatics such as 1,3-dimethoxybenzene, 2-methylthiophene, N-methylpyrrole, and 2-methylindole was investigated. In the course of these reactions an unusual migration of a phenylsulfonyl group takes place. An easy and ready for scale-up procedure for the synthesis of previously unknown β-aryl, α-phenylsulphonyl substituted α,β-unsaturated trifluoromethyl ketones is reported.     

A novel, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines

A novel, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-pyridyl)amides to produce the title compounds under mild reaction conditions in good yields.     

Total synthesis of N-malayamycin A and related bicyclic purine and pyrimidine nucleosides

Methods are described for the total synthesis of bicyclic perhydrofuropyran nucleosides as N-analogues of the naturally occurring malayamycin A. Formation of the N-nucleosides relied on the activation of thioglycosides, proceeding via sulfonium intermediates. Ring closure metathesis was used in two approaches to build the bicyclic dioxa heterocycle. Another approach relied on the use of a sugar precursor and cyclization to the bicyclic thioglycoside.     

Furan ring opening-isochromene ring closure: a new approach to isochromene ring synthesis

A new approach toward the synthesis of 1H-isochromenes based on the recyclization of the furan ring in the corresponding ortho-hydroxymethylbenzylfurans is described.     

Practical and efficient synthesis of N-halo compounds

A practical and efficient synthesis of N-halo compounds is described. Treatment of primary and secondary amines or amides with sodium hypohalite in the presence of tert-butanol and acetic acid afforded N-halo compounds in 90-100% yield.     

One-pot synthesis of benzimidazoles from gem-dibromomethylarenes using o-diaminoarenes

A one-pot synthesis of benzimidazoles from gem-dibromomethylarenes is described. The reaction shows the method to prepare a variety of benzimidazole analogues with excellent yield.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.     

Solvent-free reaction between acenaphthoquinone, various benzils and ammonium acetate: synthesis of 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones

A simple synthesis of benzo[d,e]imidazo[2,1-a]isoquinolines is described. Heating a mixture of acenaphthoquinone, a benzil, and ammonium acetate under solvent-free conditions afforded 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones in good to excellent yields.     

Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin

A stereocontrolled linear synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, diarrhetic shellfish toxins, is described. Iterative application of a tetrahydropyran synthesis by reaction of the alkylation of a sulfonyl-stabilized oxiranyl anion followed by 6-endo cyclization of a 4,5-epoxy alcohol led to the synthesis of the trans-fused hexacyclic ether system, and the seven-membered E ring was constructed by ring expansion reaction.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.     

A novel strategy for the solid-phase synthesis of cyclic lipodepsipeptides

A rapid and efficient Fmoc solid-phase synthesis of cyclic lipodepsipeptide analogue 1 to antibiotic fusaricidin A is described. Our synthetic approach includes resin attachment of the first amino acid via side chain, successful use of combination of four quasi-orthogonal removable protecting groups, stepwise solid-phase synthesis of linear peptide analogue, lipid tail attachment followed by depsipeptide bond formation and on-resin head-to-tail cyclization. Undesired O→N acyl shift, which may occur during Fmoc removal, was successfully avoided by the incorporation of the lipid tail into the linear peptide precursor prior to on-resin depsipeptide bond formation and the ring closure.     

Synthesis of substituted carbazoles and β-carbolines by cyclization of diketoindole derivatives

A new route to substituted β-carbolines and carbazoles is described. Diketoindole intermediates, prepared by Friedel-Crafts acylations of 3-substituted indoles, have been converted to 3-hydroxycarbazoles and β-carbolines in good yields, 51-96% and 82-97%, respectively. This method also allows for the formation of 4-substituted β-carbolines. The application of this methodology to the synthesis of the natural products hyellazole and 6-chlorohyellazole is also described.     

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs containing benzo[b]thiophene/benzo[b]pyrrole

The synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating benzo[b]thiophene/benzo[b]pyrrole units is described.