Dedicated to the memory of Professor Giuseppe (Pino) CapozziFor many years helicenes were regarded as an academic curiosity and a nice example of chirality without stereogenic centers. The situation changed dramatically during the last decade when fascinating optical [1] and electronic [2] properties as well as attractive applications in bioorganic chemistry [3] and asymmetric synthesis [4] emerged for these helical-shaped molecules. In parallel, new synthetic methods that circumvented the problems often related with the classical photocyclization of stilbenes, [5] including Diels-Alder reactions, [6] cyclotrimerization of alkynes, [7] carbenoid couplings, [8] radical cyclizations, [9] Pd-mediated methodologies, [10] and olefin metathesis [11] were developed. Recently, bridged triarylamine heterohelicenes of the type 1-3 have been prepared [12, 13] and studied [13, 14] in the belief that the introduction of molecular helicity, sterically driven by the increasing overlap of the terminal a and b aryl rings, influences [2b] the well known photochemical and physical properties of triarylamines. [15] As a continuation of our efforts related to sulfur heterocycles chemistry, [16] we focused on compound 3, which was prepared by building the triarylamine skeleton by employing a Buchwald-Hartwig type cross-coupling of an open iodo-aniline in the final step of a multistep reaction sequence. [13] We envisaged that derivatives like 3 could be accessible by a cascade of regioselective electrophilic aromatic sulfur insertions, [17] by applying the chemistry of the phthalimidesulfenyl chloride (4) (PhtNSCl, Pht = phthaloyl) to properly substituted triarylamines.The reaction of tris(4-methylphenyl)-(5 a) and tris(4-methoxyphenyl)amine (5 b) with one equivalent of 4 occurred smoothly at room temperature to give mono-sulfenylation ortho to the amine nitrogen atom. The bis-sulfenylation can however be achieved under more forcing reaction conditions (Scheme 1), which allowed the isolation of derivatives 6 a and 6 b in 83 % yield. In line with our previous results, [18] the introduction of a N-thiophthalimide group strongly deactivates the aromatic system, preventing further substitutions. Moreover, using triarylamines as substrates, protonation at the amine nitrogen, due to the HCl formed during sulfenylation, represents a supplementary obstacle to the polysubstitution. Indeed, we were unable to carry out an exhaustive sulfenylation of all three aromatic rings of 5 a or 5 b.The electrophilic character of sulfenamide sulfur in N-thiophthalimides can be increased by using Lewis acids.[17] Satisfyingly, reacting derivatives 6 a and 6 b with BF 3 ·Et 2 O or AlCl 3 triggers an intramolecular attack of the aromatic ring on the adjacent sulfur atom, leading to the formation of hetero[4]helicenes 7 a and 7 b in 85 and 87 % yield, respectively [a] Dr.

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A general strategy for the synthesis of diversely substituted 3,4,5‐trihydroxypiperidines (including two natural products), 5‐amino‐3,4‐dihydroxypiperidines, 3,4,5‐trihydroxypipecolic acids, and 2‐(aminomethyl)‐3,4,5‐trihydroxypiperidines is reported. The procedure used a double reductive amination or a Strecker reaction, starting from differently protected aldehydes readily synthesized on a gram scale from D‐mannose. The biological activities of the target compounds were evaluated, and some of them showed moderate inhibition of α‐L‐fucosidase and β‐glucosidase.

Thia‐bridged triarylamine hetero[4]helicenes (TBTH[4]H) are a peculiar class of geometrically stable [4]helicenes that have shown promising applications as organic electronic materials. Their structure comprises a bis‐phenothiazine moiety, with a nitrogen atom and an aromatic ring in common, forced into a helix‐shaped arrangement by four carbon–sulfur bonds. We describe a detailed study on the scope and application of the electrophilic sulfur insertion path to TBTH[4]H, with particular emphasis on the regioselective preparation of asymmetric (not dissymmetric) derivatives.

We have designed and synthesized a series of new imidazole-based compounds structurally related to an antiprotozoal agent with nanomolar activity which we identified recently. The new analogues possess micromolar activities against Trypanosoma brucei rhodesiense and Leishmania donovani and nanomolar potency against Plasmodium falciparum. Most of the analogues displayed IC50 within the low nanomolar range against Trypanosoma cruzi, with very high selectivity toward the parasite. Discussion of structure–activity relationships and in vitro biological data for the new compounds are provided against a number of different protozoa. The mechanism of action for the most potent derivatives (5i, 6a–c, and 8b) was assessed by a target-based assay using recombinant T. cruzi CYP51. Bioavailability and efficacy of selected hits were assessed in a T. cruzi mouse model, where 6a and 6b reduced parasitemia in animals >99% following intraperitoneal administration of 25 mg/kg/day dose for 4 consecutive days.

[Reaction: see text] C-Phenyl-N-erythrosylnitrone 3 behaves as a C1,C1' bis-electrophile, undergoing a double addition of Grignard reagents in a domino fashion to afford acyclic hydroxylamines 4. The reaction proceeds at 0 degrees C with variable degrees of diastereoselectivity, from moderate to good, mainly depending on the organomagnesium reagent used. The usefulness of compounds 4 has been exemplified with the synthesis of pyrroloazepine 12 through a ring closing metathesis key step.

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