Privileged medicinal scaffolds based on the structures of tetra-and penta-substituted 2-aminopyrroles were prepared via one-pot multicomponent reactions of structurally diverse aldehydes and N-(aryl-, hetaryl-, alkyl-sulfonamido)-acetophenones with activated methylene compounds. This methodology was used in a four-step synthesis of alkaloids rigidins A, B, C and D in overall yields 61%, 58%, 60% and 53%, respectively. Of these, rigidins B, C and D were synthesized for the first time.Polysubstituted pyrroles are an important class of heterocycles that display diverse pharmacological activities. 1 Furthermore, they are useful building blocks in the synthesis of natural products and heterocyclic chemistry. Although a large number of new pyrrole syntheses, 2 including multicomponent reactions (MCRs), 3 have been reported in recent years, relatively few examples are known for the preparation of polysubstituted 2-aminopyrroles. 4 Aminopyrroles are not readily available through general pyrrole ringformation methods. At the same time the 2-aminopyrrole fragment is part of many different bioactive compounds and it is recognized as a privileged medicinal structure. Known bioactivities for this class of compounds include anti-inflammatory, 5 anticancer, 6 antiviral, 7 antifungal, 8 pesticidal, 9 radioprotective, 10 MEK inhibitory, 11 MK2 inhibitory, 12 FAK, KDR and Tie2 inhibitory, 13 PDE inhibitory, 14 anti-interleukin-6, 15 TNF-α production inhibitory, 16 and afferent pelvic nerve activity inhibitory. 17 Moreover, 2-aminopyrroles are precursors for the synthesis of purine analogs -pyrrolopyrimidines, pyrrolotriazines and pyrrolopyridines. [18][19][20][21][22][23][24] Previously, we described a novel method for the synthesis of multisubstituted pyrrolines using a multicomponent reaction of various N-(aryl-and alkylsulfonamido)-acetophenones with aldehydes and malononitrile (see Table 1 graphic). 27 While the reaction is regioselective, it is not stereoselective and gives mixtures of cis and trans 2-pyrrolines, which are not easily separable. Utilizing this methodology as a starting point, we developed a new muticomponent one-pot method for the synthesis of tetra-and penta-diversely substituted 2-aminopyrroles. In addition, we utilized the new method for a short total synthesis of alkaloids rigidins A, B, C and D.Penta-substituted 2-aminopyrroles A 1-17 were prepared by a multicomponent reaction of N-(aryl-, hetaryl-and alkylsulfonamido)-acetophenones, aldehydes and cyanoacetic acid derivatives in acetonitrile, followed by oxidation with DDQ in one pot (Table 1). This threecomponent process works well for any tested combination of aliphatic, aromatic (including sterically hindered or heteroaromatic) aldehydes and malononitrile, cyanoacetamide or ethyl cyanoacetate. Because of the lower reactivity of the intermediate Knoevenagel products of cyanoacetamide or ethyl cyanoacetate, the reactions were sluggish in acetonitrile (A 16 and A 17 ). In these cases the pyrrolines were obtained in ethanol, the solvent was the...

A multicomponent reaction of 3-aminopyrazol-5-ones with substituted salicylic aldehydes and acetylacetic ester leading to the formation of novel 2,3-dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones was discovered. The elucidation of the reaction scope revealed that 5-aminopyrazoles, 3-amino-1,2,4-triazoles and 6-aminouracil could be used as the heterocyclic amine component. Selected heterocyclic products were found to possess notable antibacterial activities.

A novel reaction of indole with aryldiazonium salts leading to the formation of 2-aryl-3-(arylazo)indoles was discovered. The products were found to possess potent anti-MRSA and anti-LLVRE activities. The SAR studies indicate that the potentially metabolically labile azo functionality can be replaced with ether oxygen and thioether sulphur atoms without any loss of activity.

A new reaction of white phosphorus (P4) with elemental sulfur and thiols in the presence of different amines has been investigated. Ammonium salts of S,S′‐dialkyltetrathiophosphoric acids have been observed as main products of the reaction. Octathiotetraphosphetane ammonium salts were formed as side products. The reaction is characterized by a complete conversion of the white phosphorus and is not accompanied by the release of hydrogen sulfide. The crystal structures of both products were determined by the single crystal X‐ray diffraction. Biological activity of obtained compounds was investigated, and some promising compounds with antifungal activity identified. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:163–167, 2013; View this article online at http://wileyonlinelibrary.com. DOI 10.1002/hc.21077

Base-mediated coupling of sulfonamides of type (I) and (V) with aldehydes and activated cyanides allows new access to tetra-and pentasubstituted 2-aminopyrroles. Some of them show anticancer or antibacterial activity. The method can be applied successfully to prepare the rigidin alkaloids A, B, C, and D (XIII). -(FROLOVA, L. V.; EVDOKIMOV, N. M.; HAYDEN, K.; MALIK, I.; ROGELJ, S.; KORNIENKO, A.; MAGEDOV*, I. V.; Org. Lett. 13 (2011) 5, 1118-1121, http://dx.doi.org/10.1021/ol103149b ; Dep. Chem., N. Mex. Inst. Min. Technol., Socorro, NM 87801, USA; Eng.) -Jannicke