No abstract

As part of a program focused on the development of new antineoplastic agents based on scaffolds found in natural products, we explored the isoflavone family as potential enzyme inhibitors. We required biotin‐modified isoflavones to identify potential biological targets, and we selected the C‐2 position in isoflavones as an attachment site for an alkyl group bearing a terminal carboxylic acid to which we could attach a biotin derivative. The base‐catalyzed condensation of 2,4‐dihydroxy‐substituted deoxybenzoins with cyclic anhydrides mediated by a combination of triethylamine and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene led to an efficient synthesis of the desired 2‐(ω‐carboxyalkyl)isoflavones with functional groups at C‐5, 6 and 7 and with various substituents in the C‐3 phenyl group.

No abstract

Readily available tetrachloro-2-aza-1,3-butadienes enter into directed cyclocondensation reaction with N-phenyl-1,2-cyclopentanediamine which leads to regioselective cyclopentane annulation by the 1,3,5-triazepine. The formation of the 1,3,5-triazepine derivatives was confirmed proved by 1 H-and 13 C-NMR spectral study, elemental analysis and, in one case, single-crystal x-ray crystallographic study.

No abstract

Based on readily available

Readily available 1-aryl-1,3,4,4-tetrachloro-2-azabuta-1,3-dienes enter into a pronouncedly directed cyclocondensation reaction with 2-(w-aminoalkyl)benzimidazoles to give the corresponding seven-, eight-, and nine-membered azaheterocycles regioselectively annulated to the benzimidazole nucleus. The products thus obtained are derived from benzimidazole fused to 2H-1,3,5-triazepine, 1,3,5-triazocine, or 2H-1,3,5-triazonine, in accordance with comprehensive structural determination by spectroscopic methods and X-ray diffraction analysis.Previously we showed that the electrophilic centers at C1 and C3 in 1,3-dichloro-2-aza-1,3-dienes differ notably in their reactivity. 1,2 Nucleophilic agents first attack the center C1, whereas C3 is activated only due to the prototropy in substituted intermediates; this feature was invoked to develop a rather general approach to directed cyclocondensations (Scheme 1). Using this strategy, we purposefully designed a great number of five-and six-membered azaheterocycles. 3,4 In the present study, we have found that this method is also appropriate for the synthesis of some seven-, eight-, and nine-membered heterocyclic systems. 2-(w-Aminoalkyl)benzimidazole dihydrochlorides have been conveniently used in such syntheses: when treated with triethylamine, they produce the corresponding bases 1-3 which enter into regioselective condensations with 1-aryl-1,3,4,4-tetrachloro-2-azabuta-1,3-dienes 4, obtained from easily accessible chloral adducts of aromatic acid amides. 1 As demonstrated by Scheme 2, the first stage of the reaction between nucleophilic agents 1-3 and electrophilic substrates 4 in the presence of triethylamine leads to intermediate condensation products A which are likely to tautomerize into compounds B and then undergo annulation of the corresponding seven-, eight-, or nine-membered azaheterocycle to the benzimidazole nucleus. The hydrogen atom in the dichloromethyl group of intermediate C is sufficiently mobile to migrate thus affording the end cyclocondensation products 5-7 in high yields. Direct cyclization of intermediates A under mild conditions is unlikely judging by the fact that the related 1-functionalized 2-aza-1,3-dienes without mobile hydrogen atoms in the 1-substituent (D; Y = OAlk, NAlk 2 , SAr, etc.), are completely unreactive even to strong nucleophiles ( Figure 1). 1,2

Methyl 3-aryl-2-bromo-2-chloropropanoates can be prepared by Meerwein reaction from methyl 2-chloroacrylate and various arenediazonium salts under copper(II) bromide catalysis. The resulting readily available compounds were used as starting materials in reactions with substituted methanethiols for the construction of substituted 3-hydroxythiophenes which have not yet been accessible by other routes. Structural variety of the obtained 2-substituted 5-aryl-3-hydroxythiophenes has been achieved due to a wide range of available starting materials, including both anilines and thiols.