Adriano C. M. Baroni

Synthesis of (Z)-1-phenylseleno-1,4-diorganyl-1-buten-3-ynes: hydroselenation of symmetrical and unsymmetrical 1,4-diorganyl-1,3-butadiynes

Abstract The hydroselenation of 1-organyl-1,3-butadiynes and 1,4-diorganyl-1,3-butadiynes with the sodium phenylselenolate anion, which was generated in situ by reacting diphenyl diselenide with NaBH4 in aqueous ethanol, results in the regio-, stereo- and chemoselective formation the 1-phenylseleno-4-organyl-1-buten-3-ynes and 1-phenylseleno-1,4-diorganyl-1-buten-3-ynes of Z configuration respectively. The lack of selectivity with the 2-hydroxy-2-methyl-3,5-dodecadiyne was observed and the obtained product structures were studied in detail.

Composition of leaf and rhizome essential oils of Hedychium coronarium Koen. from Brazil.

Abstract Hydrodistillation of fresh leaves and rhizomes of Hedychium coronarium collected in the Atlantic rain forest of southeastern Brazil afforded essential oils in 0.68% and 0.20% yields, respectively. Analysis of the oils by GC and GC/MS revealed as predominant constituents in the leaf oil β-caryophyllene (43.0%), caryophyllene oxide (12.1%) and β-pinene (11.6%,), whereas 1,8-cineole (34.8%), β-pinene (16.7%) and α-terpineol (13.1%) were the major components identified in the rhizome oil.

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

Sixteen 1,4-diaryl-1,2,3-triazole compounds derived from the natural products veraguensin, grandisin and machilin G were synthesized, with yields of 78-92%. Biological activity tests against Leishmania amazonensis promastigotes showed that three of these compounds were the most active, with maximum inhibitory concentration (IC50) values of 1.1, 3.71 and 7.23 µM. One compound was highly active against Leishmania infantum, with an IC50 value of 5.2 µM, and one derivative showed an IC50 value of 28.6 µM against Trypanosoma cruzi trypomastigotes. Regarding structure-activity relationship (SAR), hybrid 1,2,3-triazolic compounds containing a methylenedioxy group, showed the best antileishmanial and antitrypanosomal activities.

Leaf Essential Oil Compositon of Pimenta pseudocaryophyllus (Gomes) L. R. Landrum Native From Brazil

Abstract Hydrodistillation of fresh leaves of Pimenta pseudocaryophyllus Gomes collected in the Atlantic Forest, south-eastern Brazil, afforded the essential oil in 0.48% yield. The major component was isolated from oil and analyzed by GC, GC/MS and NMR techniques, which revealed the compound chavibetol (70.9%). Others major constituents found were methyl eugenol (20.7%) and o-cymene (2.8%).

Four- and Eight-Carbon Homologation of Benzaldehyde by (1Z,3Z)-Butyltelluro-1,3-Butadiene: Synthesis of Navenone B: Alarm Pheromone of the Mollusk Navanax inermis

Abstract Four- and eight-carbon homologation of benzaldehydes is described. The hydrotelluration of (Z)-1-methoxy-but-1-en-3-ynes 1 afforded (1Z,3Z)-1-butyltelluro-4-methoxy-1,3-butadiene 2, this compound 2 underwent a Te/Li exchange reaction, and the butadienyllithium 3 obtained reacted with benzaldehyde to form the corresponding allylic alcohol 4 with total retention of configuration. The allylic alcohol 4a formed underwent acidic hydrolysis, resulting in 5-phenyl-(2E,4E)-dienal 5 (four-carbon homologation of benzaldehyde). Product 5 reacted with the butadienyllithium 3, affording the alcohol 9-phenyl-(1Z,3Z,6E,8E)-1-methoxy-5-hydroxy-nonatetraene 6, which was hydrolyzed or spontaneously transformed into 9-phenyl-(2E,4E,6E,8E)-tetraenal 7, completing the eight-carbon homologation of benzaldehyde. Reaction of 9-phenyl-nona-(2E,4E,6E,8E)-tetraenal 7 with methyllithium in tetrahydrofuran afforded (3E,5E,7E,9E)-10-phenyl-deca-3,5,7,9-tetraen-2-ol 8. The product of the reaction described was employed in the synthesis of (3E,5E,7E,9E)-10-phenyl-deca-3,5,7,9-tetraen-2-one 9, which is known as navenone B, an alarm pheromone of the mollusk Navanax inermis. GRAPHICAL ABSTRACT

Design, synthesis and anti-trypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G

Using bioisosterism as a medicinal chemistry tool, 16 3,5‐diaryl‐isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3‐dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T. cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L. amazonensis and L. braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5 μM against L. amazonensis and IC50 values of 1.2, 2.1 and 6.4 μM on L. braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250 μM) than pentamidine (78.9 μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.

Design, Synthesis and Anticancer Biological Evaluation of Novel 1,4-Diaryl- 1,2,3-triazole Retinoid Analogues of Tamibarotene (AM80)

We report herein the design and synthesis via click chemistry of twelve novel triazole retinoid analogues of tamibarotene (AM80) and the evaluation of their anticancer activities against six cancer cell lines: HL60, K562, 786, HT29, MCF7 and PC3. Among the synthesized compounds, two were more potent than tamibarotene against solid tumor cells, and one of them had similar potency to tamibarotene against HL60 cells. The bioisosteric exchange between the amide group and the 1,2,3-triazole core in the retinoid agent tamibarotene (AM80) reported in this work is a valid strategy for the generation of useful compounds against cancer.

Total synthesis of targretin via palladium catalyzed crosscoupling reaction of a vinyl organozinc intermediate

In the last two decades, retinoids as isotretinoin, etretinate and acitretin have been utilized in treatment of primary cutaneous T-cell lymphoma (CLTC) showing modest response in rats. 1 However, the bexarotene (targretin®) 1 emerged as a potent and highly selective ligand for the retinoid X receptors (RXRs) applied in human patients to combat the CLTC, which have become a serious public health problem.

Synthesis and evaluation of anti-leishmania activity of analogs isoxazoles derivatives of grandisin and veraguensin neolignans

Using the concept of bioisosterismo, the new analogs isoxazole were designed from the molecular modification of grandisin and veraguensin neolignans, which have a grouping that is a furan ring bioisostero isoxazole. In order to obtain more potent compounds, and better physical and chemical characteristics, our research group synthesized six analogues isoxazole neolignans. These reactions were performed of 1,3-dipolar cycloaddition between oximes chlorine and terminal acetylenes previously synthesized. The reaction system CuSO 4 .5H 2 O/Ascorbate Sodium / KHCO 3 , CH 2 Cl 2 /THF was used, and under this condition were obtained isoxazole six analogues with yields ranging from 71% To 90%. The compounds were sent for testing anti-Leishmania activity and anti-trypanosome.