Divergent Approach for Regioselective Synthesis of Linearly and Angularly Fused Benzoimidazoquinazolinones from Isatoic Anhydrides.

Ph3P-I2-mediated condensation reactions of isatoic anhydrides and o-phenylenediamines have been developed for the regioselective syntheses of a wide range of linearly and angularly fused benzoimidazoquinazolinones. The selectivity of the products relies on the generation of either highly electrophilic oxyphosphonium or less reactive imidate intermediates. A direct amine attack at the C-2 position of the oxyphosphonium intermediate presumably drives the reaction toward the linearly fused products, whereas an attack of the diamine at the C-4 position of the in situ generated cyclic imidate leads to the angularly fused derivatives. This strategy serves as a practical handle for the efficient synthesis of other related heterocycles.

Divergent Synthesis of Methylisatoid and Tryptanthrin Derivatives by Ph3P-I2-Mediated Reaction of Isatins with and without Alcohols.

A novel phosphonium-mediated reaction of isatins is described. In the presence of alcohol, the reaction proceeds to furnish C-12 modified tryptanthrin derivatives. Without alcohol, self-dimerization of isatins gives rise to tryptanthrin and its analogs. This divergent and step-economic approach provides a facile access to diverse indoloquinazoline structures including the natural alkaloids, methylisatoid and cephalanthrin B, in high yields from simple precursors under mild and metal-free reaction conditions.

Simultaneous Formation and Functionalization of Aryliminophosphoranes Using 1,3-Dihydro-1H-benzimidazol-2-ones as Precursors.

An atom- and step-economic synthesis of aryliminophosphoranes bearing ortho urea was achieved via unprecedented Ph3P-I2 mediated ring-opening of 1,3-dihydro-1H-benzimidazol-2-ones with secondary amines. Tandem aza-Wittig/heterocyclization of the functionalized aryliminophosphoranes upon treatment with isothiocyanates enables a facile access to a single regioisomer of N1-substituted 2-aminobenzimidazoles as well as fused tetracyclic quinazolinone derivatives in one-pot. 31P{1H} NMR studies suggested that the urea C-N bond of benzimidazolone is weakened by N-phosphorylation, leading to aminolysis rather than the expected deoxygenative amination.

Zwitterionic Ring-Opened Oxyphosphonium Species from the Ph3P-I2 Mediated Reactions of Benzo[d]oxazol-2(3H)-ones with Secondary Amines.

Instead of the expected substituted 2-aminobenzo[d]oxazoles, relatively stable ring-opened oxyphosphonium betaines were isolated for the first time from the Ph3P-I2-mediated reactions of benzo[d]oxazol-2(3H)-ones with acyclic secondary amines. The structure of one of these compounds was unambiguously confirmed by single-crystal X-ray analysis. Thermolysis of the betaines gave rise to 2-dialkylaminobenzoxazoles with concomitant loss of triphenylphosphine oxide, suggesting their possible role as intermediates in an alternative reaction path.

Metal-Free Synthesis of 2- N, N-Dialkylaminobenzoxazoles Using Tertiary Amines as the Nitrogen Source.

The unprecedented reaction of tertiary amines with 2(3 H)-benzoxazolones has been investigated. In the presence of the Ph3P-I2 reagent system, the reaction of both acyclic and cyclic aliphatic tertiary amines led to the formation of 2- N, N-dialkylaminobenzoxazoles with the selective cleavage of an alkyl group. Especially, N-(2-iodoethyl)piperazinyl derivatives were rapidly produced in good yields when using DABCO as the nitrogen source. Only in the cases when the nucleophilicity of the substrates exceeds that of the amine, competitive self-condensation of benzoxazolones then proceeds preferentially. 31P{1H}-NMR study suggested the involvement of an aryloxyphosphonium intermediate and/or possibly 2-iodobenzoxazole which activates the C-2 position of benzoxazolones toward nucleophilic aromatic substitution.

A convenient one-pot synthesis of N-substituted amidoximes and their application toward 1,2,4-oxadiazol-5-ones.

The first direct one-pot approach for the synthesis of N-substituted amidoximes from secondary amides or the intermediate amides has been developed. Through the Ph3P-I2-mediated dehydrative condensation, a variety of N-aryl and N-alkyl amidoximes (R1(C[double bond, length as m-dash]NOH)NHR2, where R1 or R2 = aryl, alkyl, or benzyl) were readily afforded under mild conditions and short reaction times. The synthetic application of the obtained amidoximes has also been demonstrated through the formation of 1,2,4-oxadiazolones via base-mediated carbonylative cyclization with 1,1'-carbonyldiimidazole.

Application of N-Acylbenzotriazoles in the Synthesis of 5-Substituted 2-Ethoxy-1,3,4-oxadiazoles as Building Blocks toward 3,5-Disubstituted 1,3,4-Oxadiazol-2(3H)-ones.

5-Substituted-2-ethoxy-1,3,4-oxadiazoles were conveniently prepared through a one-pot sequential N-acylation/dehydrative cyclization between ethyl carbazate and N-acylbenzotriazoles in the presence of Ph3P-I2 as a dehydrating agent. Subsequent treatment with a stoichiometric amount of alkyl halides (X = Cl, Br, I) enables a rapid access to a variety of 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-ones in good to excellent yields.

Ph3P/I2-Mediated Synthesis of N,N',N″-Substituted Guanidines and 2-Iminoimidazolin-4-ones from Aryl Isothiocyanates.

A convenient one-pot procedure for the synthesis of acyclic and cyclic guanidines mediated by the Ph3P/I2 system is described. Sequential condensation of aryl isothiocyanates with amines followed by dehydrosulfurization and guanylation could lead to both symmetric and unsymmetric N,N',N″-substituted derivatives. Through a tandem guanylation-cyclization, a series of 2-iminoimidazolin-4-ones could also be prepared in good yields from the reaction of aryl isothiocyanates with amino acid methyl esters.

Approach to the Synthesis of 2,3-Disubstituted-3H-quinazolin-4-ones Mediated by Ph3P-I2.

Readily available N-substituted amides or their requisite carboxylic acids or acid chlorides have been used to construct 2,3-disubstituted-3H-quinazolin-4-ones in a one-pot procedure. Key transformation in this convergent approach involves Ph3P-I2-mediated formation of amidine upon condensation of an amide or the intermediate amide with methyl anthranilate. Cyclization of the amidine-tethered anthranilate then affords 2,3-disubstituted-3H-quinazolin-4-ones in good to excellent yields under mild conditions.

Ultrasound-Assisted Solvent-Free Parallel Synthesis of 3-Arylcoumarins Using N-Acylbenzotriazoles.

An ultrasound-assisted one-pot acylation/cyclization reaction between N-acylbenzotriazoles and 2-hydroxybenzaldehydes has been developed for the synthesis of substituted 3-arylcoumarins. Using ultrasound not only allows rapid and clean conversion but also simplifies experimental setup and parallel workup leading to rapid generation of 3-arylcoumarin libraries under mild, solvent-free, and chromatography-free conditions.

Cowabenzophenones A and B, two new tetracyclo[7.3.3.3(3,11).0(3,7)]tetradecane-2,12,14-trione derivatives, from ripe fruits of Garcinia cowa.

Two new tetracyclo[7.3.3.3(3,11).0(3,7)]tetradecane-2,12,14-trione derivatives, cowabenzophenones A (1) and B (2), were isolated from ripe fruits of Garcinia cowa Roxb. Their structures were determined by spectroscopic methods. The tetracyclo[7.3.3.3(3,11).0(3,7)]tetradecane-2,12,14-trione skeleton from the Garcinia genus is reported for the first time.

Clausenawallines G-K, carbazole alkaloids from Clausena wallichii twigs.

Five carbazole alkaloids, clausenawallines G-K (1-5), along with 12 known alkaloids (6-17) were isolated from the twigs of Clausena wallichii. Their structures were established using spectroscopic methods and the antibacterial activity of compounds 1-5 was evaluated.

Rearranged benzophenones and prenylated xanthones from Garcinia propinqua twigs.

The first phytochemical investigation of Garcinia propinqua has led to the isolation and identification of three new compounds, including two rearranged benzophenones, doitunggarcinones A (1) and B (2), and a xanthone, doitunggarcinone C (3), together with seven known compounds (4-10). The structures of 1-3 were elucidated on the basis of spectroscopic methods, including UV, IR, NMR, and MS. The antibacterial activity of the 10 isolates was evaluated against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466, and methicillin-resistant Staphylococcus aureus (MRSA) SK1.

Antibacterial compounds from Zanthoxylum rhetsa.

A new amide, zanthorhetsamide (1), along with nine known compounds (2-10) was isolated from the roots and stem barks of Zanthoxylum rhetsa. The structure was characterized by spectroscopic methods. In addition, the antibacterial activity of the isolates was evaluated. Dihydrochelerythrine (4) exhibited strong activity against methicillin-resistant Staphylococcus aureus SK1 and moderate activity against Escherichia coli TISTR 780 with MIC values of 8 and 16 µg/mL, respectively.

Antibacterial carbazole alkaloids from Clausena harmandiana twigs.

Three new carbazole alkaloids, harmandianamines A-C (1-3), together with fifteen known compounds (4-18) were isolated from the twigs of Clausena harmandiana. The structures were elucidated by spectroscopic methods, including UV, IR, NMR, and MS. The antibacterial activity against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466 and methicillin-resistant S. aureus (MRSA) SK1 of some isolated compounds was also evaluated. Compound 6 exhibited significant antibacterial activity against MRSA SK1 with an MIC value of 0.25 µg/mL which higher than that of standard drug, vancomycin (MIC value=1 µg/mL) whereas compounds 14 and 5 showed strong activity with MIC values of 4 and 8 µg/mL, respectively. Only compound 14 showed strong antibacterial activity against S. aureus TISTR 1466 with an MIC value of 4 µg/mL.

Bioactive carbazole alkaloids from Clausena wallichii roots.

Four new carbazole alkaloids, clausenawallines C-F (1-4), along with 18 known compounds (5-22) were isolated from the roots of Clausena wallichii. Compounds 3, 9, and 22 exhibited significant antibacterial activity against methicillin-resistant Staphylococcus aureus SK1 (MRSA SK1) and Staph. aureus TISTR 1466 with MIC values in the range 4-16 µg/mL, whereas compound 4 showed the highest cytotoxicity against oral cavity cancer (KB) and small-cell lung cancer (NCI-H187) with IC(50) values of 10.2 and 4.5 µM, respectively.

(1R,3R,4R,6S)-4-(7-Meth-oxy-2-oxo-2H-chromen-6-yl)-1-methyl-3,6-dioxa-bicyclo-[3.1.0]hexan-2-yl acetate.

In the title compound, C17H16O7, which was isolated from the leaves of Micromelum integerrimum, the furan ring adopts an envelope conformation with the O atom as the flap. An intra-molecular C-H⋯O hydrogen bond occurs. The carbonyl O atom is disordered in a 0.57 (8):0.43 (8) ratio. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds into a C(10) chain along [010].

Antibacterial dihydrobenzopyran and xanthone derivatives from Garcinia cowa stem barks.

Two new compounds, garciniacowol (1) and garciniacowone (2) along with 15 knowncompounds were isolated from the stem barks of Garcinia cowa. Their structures weredetermined by intensive spectroscopic methods. The structure of 1 was a symmetrical dimericdihydrobenzopyran derivative, whereas the framework of 2 was a triprenyl caged-xanthoneprecursor. The antibacterial activities against Escherichia coli TISTR 780, Salmonellatyphimurium TISTR 292, Staphylococcus aureus TISTR 1466, and methicillin-resistant S. aureus(MRSA) SK1 of the isolated compounds were also evaluated. Compounds 2 and 9 exhibitedgood antibacterial activity against MRSA SK1 with the same minimum inhibitory concentration(MIC) value of 2 µg/mL. Moreover, compound 2 also showed good antibacterial activityagainst S. aureus with an MIC value of 2 µg/mL.

Generation of ortho-quinone methides by p-TsOH on silica and their hetero-Diels-Alder reactions with styrenes.

2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the ortho-quinone methides (o-QMs) which, in turn, were generated by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized on silica (PTS-Si) in toluene under mild conditions (0 degrees C to rt). The corresponding chromans were obtained in moderate to excellent yields (42-97%) and in moderate to excellent diastereoselectivity (up to >99:1).