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 an efficient relay synthesis of the pyrrole containing alkaloids polycitone A and B

A new and efficient relay synthesis of the marine natural products polycitone A and B is described. The new strategy relies on the formation of 2,4-disubstituted pyrroles from a vinamidinium salt followed by electrophilic substitution at the 5-position of the pyrrole and Suzuki coupling at the 4-position to produce the tetrasubstituted heterocycle efficiently and with complete control of regiochemistry.     

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.     

Synthesis and characterization of new derivatives of bis(1,4-diazepinium) salts and bis(γ-substituted pentamethine cyanine(dyes using vinamidinium salt

The preparation of several bis(1,4-diazepinium) salts from the reaction of three 1,2-diamines with a bis(vinamidinium) salt is described. Bis(γ-substituted pentamethine cyanine(dyes are also prepared from the reaction of vinamidinium salt with 1,2-dimethylquinolinium perchlorate and 1,2,3,3-tetramethyl-3H-indolium perchlorate. Data from elemental analyzes, IR, ¹H-NMR, ¹³C-NMR, and mass spectra (MS) confirm the molecular structure of the obtained 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.     

Two Convenient Syntheses of 2-Aryl-1-Cyano-1-Propenes From Quaternary Ammonium Salts

Two readily available and different quaternary ammonium salts have been prepared by the alkylation of vinamidinium salt reduction products. These salts have been successfully converted to 2-aryl-1-cyano-1-propenes and this methodology represents a clean and efficient procedure for the construction of such systems.     

Hydrogen iodide-promoted reduction of beta-chlorovinamidinium salts

HI cleanly reduced chlorovinamidinium salts to the vinamidinium salt in essentially quantitative assay yield and 55-85% isolated yield following recrystallization. The reaction proceeds via protonation of the beta-carbon atom of the vinamidinium and dechlorination via the formation of I-Cl.     

A [2 + 2] cycloaddition route to dimethylaminomethylene vinamidinium salts

[reaction: see text] Trifluoropropanoic acid reacts with 1 equiv of POCl3 in DMF to generate the trifluoromethyl enamine (7). At this stage, two reaction manifolds are available. The expected reaction with additional POCl3 generates the 2-trifluoromethyl vinamidinium salt (3c). However, thermally driven loss of fluoride generates an iminium ion, which sets the stage for a [2 + 2] cycloaddition to ultimately generate the dimethylaminomethylene vinamidinium salt (1).     

Xanthene-based ligand with two adjacent beta-diiminato binding sites

A novel potential ligand has been designed where two beta-dialdimine units are linked by a xanthene backbone (H2Xanthdim). The synthesis proceeds via a double vinamidinium salt and the products of its hydrolysis (containing eneamine/malonaldehyde units), which were converted into H2Xanthdim via a reaction with 2,3-dimethylaniline. The reaction of H2Xanthdim with n-butyllithium yields ((Et2O)Li)2Xanthdim, which was isolated and crystallized. The crystal structures of both H2Xanthdim and its lithium salt are discussed.     

Synthesis of alkylpyrroles by use of a vinamidinium salt

The synthesis of alkyl-substituted 2-pyrrolecarboxylate esters has been accomplished by the condensation reaction of a symmetrical vinamidinium salt and glycine ester derivatives.     

Efficient One-Pot Synthesis of Substituted Pyrido[2,3-d]pyrimidines from Vinamidinium and Chloropropeniminium Salts

A novel and efficient one-pot preparation of 6-substituted pyrido-[2,3-d]pyrimidines by cyclocondensation of 6-amino-1,3-dimethyluracil with symmetrical vinamidinium salts under basic conditions has been developed. Regioselectivity was observed with an unsymmetrical chloropropeniminium salt.     

Conversion of L-proline to pyrrolyl-2-carboxyl-S-PCP during undecylprodigiosin and pyoluteorin biosynthesis

Several medically and agriculturally important natural products contain pyrrole moieties. Precursor labeling studies of some of these natural products have shown that L-proline can serve as the biosynthetic precursor for these moieties, including those found in coumermycin A(1), pyoluteorin, and one of the pyrroles of undecylprodigiosin. This suggests a novel mechanism for pyrrole biosynthesis. The biosynthetic gene clusters for these three natural products each encode proteins homologous to adenylation (A) and peptidyl carrier protein (PCP) domains of nonribosomal peptide synthetases in addition to novel acyl-CoA dehydrogenases. Here we show that the three proteins from the undecylprodigiosin and pyoluteorin biosynthetic pathways are sufficient for the conversion of L-proline to pyrrolyl-2-carboxyl-S-PCP. This establishes a novel mechanism for pyrrole biosynthesis and extends the hypothesis that organisms use A/PCP pairs to partition an amino acid into secondary metabolism.     

Synthesis of new metal-free 1,2,4,5,9,10,12,13-octaaza[16]annulene derivatives using the reaction of vinamidinium salts with thiocarbohydrazide

A new series of marcocyclic ligands, 1,2,4,5,9,10,12,13-octaaza[16]annulene derivatives were synthesized by using the condensation reaction of the correspondingly [2+2] 2-heteroaryl-substituted vinamidinium salts or phenyl vinamidinium salts and derivatives or halo-substituted vinamidinum salt [1A-10A] with thiocarbohydrazide in ethanolic medium under mild condition. Metal complexes were formed by reacting of ethanolic solution of Co, Ni, and Zn with macrocyclic ligand in ethanolic medium under mild condition. Purposed complexes have been characterized with the help of elemental analyses, comparative absorption band of ν(C=N), mass, and NMR. Geometry and complex formulation are out of scope of this work. The biological activities of carohydrazide and thiocarbohydrazide base of the ligands and purposed complexes such as antimicrobial, antitumor, and insecticides have attracted significant attention in bioorganic chemistry.     

Polypyrrole-coated natural rubber latex by admicellar polymerization

Admicellar polymerization has been used for the preparation of an electrically conductive polypyrrole coating on latex particles. An anionic surfactant, sodium dodecyl sulfate (SDS), was adsorbed onto natural rubber (NR) latex particles to form the surfactant bilayers after adjusting the pH below the point of zero charge of the latex surface. Adsorption of SDS and pyrrole adsolubilization were determined as a function of pyrrole and sodium chloride concentrations. Pyrrole caused a decrease in SDS adsorption at equilibrium. Sodium chloride increased the surfactant adsorption and the pyrrole adsolubilization. Thermogravimetric results showed the presence of polypyrrole. The conductivity of the polypyrrole-coated NR latex film prepared by admicellar polymerization without salt was the lowest; however, with salt addition, the conductivity of the film improved significantly. The oxidative polymerization technique resulted in a relatively higher conductivity than oxidative admicellar polymerization.     

Iridium‐Catalyzed Enantioselective Synthesis of Pyrrole‐Annulated Medium‐Sized‐Ring Compounds

Enantioselective synthesis of pyrrole‐annulated medium‐sized‐ring compounds by an iridium‐catalyzed allylic dearomatization/retro‐Mannich/hydrolysis sequence is presented. Various substituted pyrrole‐annulated seven‐ and eight‐membered‐ring products were obtained under mild reaction conditions with moderate to good yields and excellent enantioselectivity. Additionally, these products contain a scaffold widely distributed in natural products and biologically active compounds. The current method provides a convenient way for accessing such pyrrole‐anuulated medium‐sized‐ring compounds.     

Scope and mechanism of direct indole and pyrrole couplings adjacent to carbonyl compounds: total synthesis of acremoauxin A and oxazinin 3

Full details are provided for a recently invented method to couple indoles and pyrroles to carbonyl compounds. The reaction is ideally suited for structurally complex substrates and exhibits high levels of chemoselectivity (functional group tolerability), regioselectivity (coupling occurs exclusively at C-3 of indole or C-2 of pyrrole), stereoselectivity (substrate control), and practicality (amenable to scaleup). In addition, quaternary stereocenters are easily and predictably generated. The reaction has been applied to a number of synthetic problems including total syntheses of members of the hapalindole family of natural products, ketorolac, acremoauxin A, and oxazinin 3. Mechanistically, this coupling protocol appears to operate by a single electron-transfer process requiring generation of an electron-deficient radical adjacent to a carbonyl which is then intercepted by an indole or pyrrole anion.     

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.     

Facile synthesis of novel 3-substituted pyrido[1,2-a]pyrimidinium salts using vinamidinium salts

Pyrido[1,2-a]pyrimidinium salt derivatives 2a–f were prepared in good yields by condensation of 2-aminopyridine with 2-substituted vinamidinium salt derivatives 1a–f. The purity and the structure of the synthetized compounds were ascertained by elemental analysis, mass spectrometry, infrared, and NMR (¹H and ¹³C 400?MHz) spectroscopy.     

Synthesis of N‐Aryl Formyl Pyrrole from γ‐Lactam Derivatives: A Highlight

Pyrrole containing analogs are considered as a potential source of biologically active compounds and have significant set of advantageous properties and are found in many natural products. A number of methods have been reported till now to synthesize pyrrole and pyrrole containing analogs. This review article outlines highlight the recent progresses in pyrrole synthesis from γ‐lactam derivatives.     

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.