Luiz Fernando Toneto Novaes

Total Synthesis and Tentative Structural Elucidation of Cryptomoscatone E3: Interplay of Experimental and Computational Studies

A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions.

Total synthesis and stereochemical assignment of cryptolatifolione

An enantioselective total synthesis of cryptolatifolione and its C-8 epimer is presented in a protecting-group-free fashion. The synthesis relied on the use of a catalytic double Krische allylation, catalytic olefin metathesis and a C–H oxidation. Comparison of spectroscopic data of the synthetic isomers and natural product made possible the unambiguous elucidation of the absolute configuration of cryptolatifolione.

(-)-Tarchonanthuslactone: Design of New Analogues, Evaluation of their Antiproliferative Activity on Cancer Cell Lines, and Preliminary Mechanistic Studies.

Natural products containing the α,β‐unsaturated δ‐lactone skeleton have been shown to possess a variety of biological activities. The natural product (−)‐tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total syntheses of dihydropyran‐2‐ones modeled on the structure of 1 were undertaken. These compounds were obtained in overall yields of 17–21 % based on the Keck asymmetric allylation reaction and were evaluated in vitro against eight different cultured human tumor cell lines. We further conducted initial investigation into the mechanism of action of selected analogues. Dihydropyran‐2‐one 8 [(S,E)‐(6‐oxo‐3,6‐dihydro‐2H‐pyran‐2‐yl)methyl 3‐(3,4‐dihydroxyphenyl)acrylate], a simplified analogue of (−)‐tarchonanthuslactone (1) bearing an additional electrophilic site and a catechol system, was the most cytotoxic and selective compound against six of the eight cancer cell lines analyzed, including the pancreatic cancer cell line. Preliminary studies on the mechanism of action of compound 8 on pancreatic cancer demonstrated that apoptotic cell death takes place mediated by an increase in the level of reactive oxygen species. It appears as though compound 8, possessing two Michael acceptors and a catechol system, may be a promising scaffold for the selective killing of cancer cells, and thus, it deserves further investigation to determine its potential for cancer therapy.

Formal Total Synthesis of Actinoranone and Asymmetric Synthesis of Labda-7,13-(E)-dien-15-ol

The syntheses of the polyketide and terpenoid fragments of actinoranone are reported in a concise fashion, relying on catalytic methods. Minimization on the use of protecting groups and redox reactions allowed the synthesis of the carbon backbone of actinoranone in 20 steps (11 steps for LLS). The asymmetric synthesis of labda-7,13-(E)-dien-15-ol is also disclosed.

(−)-Tarchonanthuslactone Exerts a Blood Glucose-Increasing Effect in Experimental Type 2 Diabetes Mellitus

A number of studies have proposed an anti-diabetic effect for tarchonanthuslactone based on its structural similarity with caffeic acid, a compound known for its blood glucose-reducing properties. However, the actual effect of tarchonanthuslactone on blood glucose level has never been tested. Here, we report that, in opposition to the common sense, tarchonanthuslactone has a glucose-increasing effect in a mouse model of obesity and type 2 diabetes mellitus. The effect is acute and non-cumulative and is present only in diabetic mice. In lean, glucose-tolerant mice, despite a slight increase in blood glucose levels, the effect was not significant.

Formal Total Synthesis of Actinoranone: Synthesis Approaches and Cytotoxic Studies

This article describes our efforts toward the total synthesis of actinoranone. Our synthesis strategies rely on a convergent route to connect the terpenoid and polyketide fragments, employing catalysis and powerful classical reactions for the assembly of these key fragments. A new transformation was disclosed during this work, a domino ring-opening and esterification. Initial cytotoxic studies for the selected synthesis intermediates are also presented.