The application of vinylogous iminium salt derivatives to an efficient synthesis of the pyrrole containing alkaloids Rigidin and Rigidin E

Studies directed on the synthesis of the pyrrole containing marine natural products Rigidin and Rigidin E via vinylogous iminium salts are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole from a vinamidinium salt followed by acylation at the 5-position of pyrrole. Halogenation and aminocarbonylation at the 3-position of pyrrole followed by hydrolysis of the ester group at C-2 and subsequent Curtius rearrangement generates the pyrrolopyrimidine skeleton. A final deprotection step completes the synthesis of Rigidin and Rigidin E.     

The application of vinylogous iminium salt derivatives to efficient formal syntheses of the marine alkaloids lamellarin G trimethyl ether and ningalin B

Studies directed at the synthesis of lamellarin G trimethyl ether and ningalin B via vinylogous iminium salt derivatives are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 1,2,3,4-tetrasubstituted pyrrole from a vinylogous iminium salt or vinylogous iminium salt derivative. Subsequent transformations of these highly substituted pyrroles lead to efficient and regiocontrolled formal syntheses of the respective pyrrole containing natural products.     

The application of vinylogous iminium salt derivatives to the synthesis of Ningalin B hexamethyl ether

A vinylogous iminium salt derivative has been used to prepare a 2,3,4-trisubstituted pyrrole synthon in a regioselective, efficient and convenient manner. This pyrrole synthon was subsequently converted to the multidrug-resistant (MDR) reversal agent, Ningalin B hexamethyl ether, via alkylation, hydrolysis and oxidative lactonization steps. This methodology provides an alternative pathway to this important class of pyrrole containing marine natural products.     

The Application of Vinylogous Iminium Salt Derivatives and Microwave Accelerated Vilsmeier-Haack Reactions to Efficient Relay Syntheses of the Polycitone and Storniamide Natural Products

Studies directed at the synthesis of polycitone and storniamide natural products via vinylogous iminium salts and microwave accelerated Vilsmeier-Haack formylations are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 2,3,4-trisubstituted pyrrole from a vinamidinium salt or vinamidinium salt derivative followed by formylation at the 5-position of the pyrrole. Subsequent transformations of the selectively formylated pyrroles lead to efficient and regiocontrolled relay syntheses of the respective pyrrole containing natural products.     

Annulation of pyrrole: application to the synthesis of indolizidine alkaloids

The nucleophilicity of pyrrole has been exploited to rapidly assemble the bicyclic skeleton of the indolizidine alkaloids. The key sequence is the annulation of a second ring onto pyrrole from a γ-lactone and has been exploited in the synthesis of the natural products (±)-monomorine and (±)-indolizidine 209D.     

Total syntheses of the marine pyrrole alkaloids polycitone A and B

Polycitone B (2) was obtained in four steps from pyrrole dicarboxylic acid 3, including Friedel-Crafts reaction of the corresponding acid chloride with anisole. The conversion of 2 into polycitone A (1) was achieved in two steps via Mitsunobu alkylation of the pyrrolic NH group. The synthesis of polycitone A proceeds in 18% overall yield and offers the possibility of varying the substituents on the pyrrole ring.     

Formyl group activation of a bromopyrrole ester in Suzuki cross-coupling reactions: application to a formal synthesis of Polycitone A and B and Polycitrin A

A new pyrrole building block is described, which allows for the regiospecific synthesis of 2,3,5-trisubstituted pyrroles and 2,3,4,5-tetrasubstituted pyrroles. Optimization studies are presented for the preparation of the pyrrole building block along with the evaluation of various cross-coupling conditions and cross-coupling agents. A short, formal synthesis of the natural products Polycitone A, Polycitone B, and Polycitrin A from the pyrrole building block is also described.     

The application of formyl group activation of bromopyrrole esters to formal syntheses of lycogarubin C,permethyl storniamide A and lamellarin G trimethyl ether

Lycogarubin C, permethyl storniamide A, and lamellarin G trimethyl ether are pyrrole containing, natural products, which exhibit interesting biological properties. Such properties include anti-tumor activity on a variety of cancer cell lines including those that confer drug resistance, inhibition of HIV integrase, and vascular disrupting activity. We now describe the use of methyl and ethyl 3-bromo-2-formylpyrrole-5-carboxylate as building blocks for the formal synthesis of these three highly functionalized, bioactive pyrroles. These new building blocks will now provide ready access to the natural products and many novel analogs due to the ability to easily modify positions 2,3,4, and 5 of the pyrrole core.     

Remarkable solvent effect in Barton-Zard pyrrole synthesis: application in an efficient one-step synthesis of pyrrole derivatives

A unique solvent effect encountered in the Barton-Zard pyrrole synthesis was exploited to develop an efficient synthesis of pyrrole-2-esters. The chemistry was extended to a one-pot synthesis of pyrrole-2,4-dicarboxylates.     

Application of vinylogous carbamates and vinylogous aminonitriles to the regiospecific synthesis of uniquely functionalized pyrroles and quinolones

Pyrroles and quinolones represent core structures, which are routinely found in both natural and synthetic bioactive substances. Consequently, the development of efficient and regiospecific methods for the preparation of such heterocycles with unique functionality is of some importance. We describe herein the regiospecific synthesis of 1,2,3,4-tetrasubstituted pyrroles containing polar substituents and such products are prepared from vinylogous carbamates and vinylogous aminonitriles. We also describe the regiospecific synthesis of 3-aryl containing 1,3,6-trisubstituted quinolones from vinylogous carbamates. The use of an amine exchange reaction to prepare precursors for the pyrrole and quinolone forming cyclizations represents a key factor in the strategy.     

Concise total synthesis of phidianidine A and B

The shortest total synthesis of cytotoxic indole alkaloids phidianidine A and B is described. Rapid assembly of the 1,2,4-oxadiazole core from a novel N-hydroxyguanidine and the corresponding indole-3-acetic acid chloride led to formal syntheses of phidianidine A and B in only three steps from known compounds. Deprotection under standard conditions provided the trifluoroacetate salts of phidianidine A and B in quantitative yield.     

Microwave-assisted ring-closing metathesis of diallylamines: a rapid synthesis of pyrrole and pyrroline derivatives

The ring-closing metathesis (RCM) reactions of diallylamines occurred under controlled microwave irradiation. In addition to the high reaction rate, the key features of the reaction are that it can be carried out without deactivation of the substrates and without the use of Lewis acids.     

The application of vinamidinium salts to the synthesis of 2,4-disubstituted thiophenes

The synthesis of 2,4-disubstituted thiophenes by the condensation of symmetrical vinamidinium salts with methyl thioglycolate has been accomplished for the first time. Simple experimental conditions were used to prepare seven different methyl 4-aryl-2-thiophenecarboxylates, three of which are new compounds.     

Copper catalyzed synthesis of highly substituted pyrrole and isoindole derivatives

We have developed an efficient synthesis of highly substituted pyrrole and isoindole derivatives using copper(I) catalyst. This methodology is helpful for the synthesis of some quinones bearing annealed N-heterocyclic natural products.     

Polygodial: A viable natural product scaffold for the rapid synthesis of novel polycyclic pyrrole and pyrrolidine derivatives

The dialdehyde polygodial was utilised as a chiral scaffold for the unified synthesis of novel polycyclic pyrrole and pyrrolidine derivatives. Mechanistic insight into the reaction of primary amines with this dialdehyde was obtained. In addition, one of these polycyclic pyrroles was transformed further to prepare novel pentacyclic frameworks.     

Clean and efficient microwave-solvent-free conversion of homochiral amines, α-amino alcohols and α-amino acids to their chiral 2-substituted pyrrole derivatives

Efficient synthesis of 1,2-disubstituted homochiral pyrroles has been achieved by a two-component coupling of chloroenones and amine compounds on the surface of silica gel without any solvent under microwave irradiation.     

Phosphole, pyrrole, and their tetrahydro derivatives: A theoretical study of their properties

A theoretical analysis of four molecules (phosphole, phospholane, pyrrole, and pyrrolidine) in their ground and transition states has been carried out. The transition state of phosphole is highly aromatic and a partition of its energy into atomic contributions reveals that it is the phosphorus atom that is responsible for this observation.     

TiO2-coated graphene oxide-molybdate complex as a new separable nanocatalyst for the synthesis of pyrrole derivatives by Paal-Knorr reaction

The preparation of chemical and pharmaceutical compounds through organic reactions has always been associated with the production of environmental waste. Growth population and concerns about ecological pollution increase the interest in using heterogeneous solid catalysts with capabilities such as increasing reaction efficiency and reducing the production of by-products, as well as the ability to separate and reuse. To develop and benefit such catalysts as much as possible, in this study, using graphene oxide (GO) as a support, we succeeded in preparing a heterogeneous catalyst with a high contact surface, excellent performance, and recyclability. Graphene oxide nanosheets were synthesized according to Hummer’s method. hexamolybdate anions ([n-Bu₄N]₂[Mo₆O₁₉]) were placed on this support as a catalytically active site using linkers. The structure of this catalyst was confirmed by XRD, FT-IR, EDS, SEM, TEM, TGA, Raman, and nitrogen adsorption–desorption analyses, and it was used to produce pyrroles by the Paal-Knorr method. The performance of the synthesized nanocatalyst was satisfactory for all the derivatives studied. Recovery and reuse of GO@TiO₂@(CH₂)₃N = Mo[Mo₅O₁₈] after catalytic reactions were examined. This catalyst could be quickly recovered by simple filtration and recycled ten times without significant loss of its catalytic activity.     

Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A

The highly stereoselective attachment of isoquinoline onto the steroidal framework of cortistatin A has been achieved. Our strategy features a Ce-mediated nucleophilic addition of an isoquinoline unit to the sterically congested ketone followed by formation of the phenyl thiocarbamate, and subsequent stereoselective radical reduction. The new method results in a formal total synthesis of cortistatin A.     

Stereoselective synthesis of the cyclic ether core of (+)-laurenyne

A concise enantioselective synthesis of the cyclic ether core of the marine natural product (+)-laurenyne has been accomplished using ring-closing metathesis for medium-ring construction.