RESUMO
The scientific activity carried out over forty-five years on stemodane diterpenes and diterpenoids structure elucidation, biogenesis, biosynthesis, biological activity and biotransformations was reviewed.
Assuntos
Diterpenos/química , Diterpenos/isolamento & purificação , Metaboloma , Vias Biossintéticas , Biotransformação/efeitos dos fármacos , Diterpenos/metabolismo , Diterpenos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Metaboloma/efeitos dos fármacosRESUMO
(+)-(S) and (-)-(R)-5-methyl-Wieland-Miescher ketone (+)-1 and (-)-1, are important synthons in the diastereo and enantioselective syntheses of biological and/or pharmacological interesting compounds. A key step in these syntheses is the chemoselective C(1)O acetalization to (+)-5 and (-)-5, respectively. Various procedures for this transformation have been described in the literature. Among them, the classical procedure based on the use of 1,2-ethanediol and TsOH in refluxing benzene in the presence of a Dean-Stark apparatus. Within our work on bioactive natural products, it occurred to us to observe the partial racemization of (+)-5 in the course of the acetalization of (+)-1 by means of the latter methodology. Aiming to investigate this drawback, which, to our best knowledge, has no precedents in the literature, we acetalized with 1,2-ethanediol and TsOH in refluxing benzene and in the presence of a Dean-Stark apparatus under various experimental conditions, enantiomerically pure (+)-1. It was found that the extent of racemization depends on the TsOH/(+)-1 and 1,2-ethanediol/(+)-1 ratios. Mechanism hypotheses for this partial and unexpected racemization are provided.
Assuntos
Etilenoglicol/química , Cetonas/química , Modelos Químicos , EstereoisomerismoRESUMO
: In this article the scientific activity carried out on stemarane diterpenes and diterpenoids, isolated over the world from various natural sources, was reviewed. The structure elucidation of stemarane diterpenes and diterpenoids was reported, in addition to their biogenesis and biosynthesis. Stemarane diterpenes and diterpenoids biotransformations and biological activity was also taken into account. Finally the work leading to the synthesis and enantiosynthesis of stemarane diterpenes and diterpenoids was described.
Assuntos
Antibacterianos/química , Diterpenos/química , Extratos Vegetais/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Calceolariaceae/química , Calceolariaceae/metabolismo , Diterpenos/síntese química , Diterpenos/farmacologia , Extratos Vegetais/farmacologia , Scrophulariaceae/química , Scrophulariaceae/metabolismoRESUMO
In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned.
Assuntos
Abietanos/química , Abietanos/síntese química , Calceolariaceae/química , Plantaginaceae/químicaRESUMO
The first synthesis of (+)-19-acetoxystemodan-12-ol (1), a stemodane diterpenoid isolated from Stemodia chilensis, is described. The structure was supported by an X-ray crystallographic analysis of intermediate (+)-9a, which confirmed the proposed structure and excluded the structure of (-)-19-hydroxystemod-12-ene as a possible candidate for the Chilean Calceolaria diterpenoid to which the (-)-19-hydroxystemar-13-ene structure (9b) had been erroneously assigned.
Assuntos
Abietanos/química , Plantaginaceae/química , Chile , Cristalografia por Raios X , Diterpenos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , EstereoisomerismoRESUMO
The problem of constructing diastereoselectively the C/D ring system of stemarane diterpenes from a bicyclo[2.2.2]octane intermediate was solved resulting in very simple synthesis of (+)-13-stemarene 1. The obtaining of the latter represents also a formal synthesis of (+)-18-deoxystemarin 2. In the key step, the epimeric mixture 10, dissolved in toluene, was converted by the action of TsOH into (+)-stemar-13-en-15-one 28.
Assuntos
Diterpenos/síntese química , Ciclização , Diterpenos/química , Estrutura Molecular , EstereoisomerismoRESUMO
6-endo- and 6-exo-Hydroxybicyclo[2.2.2]octan-2-one and 1-methyl-6-endo- and 6-exo-hydroxybicyclo[2.2.2]octan-2-one ethylene acetals and ethylene dithioacetals 1-4 have been characterized by 1D and 2D NMR methods.
Assuntos
Acetais/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Etilenos/química , Enxofre/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
[reaction: see text] A series of 6-exo-acetoxybicyclo[2.2.2]octan-2-ones were converted into the corresponding 6-exo-hydroxybicyclo[2.2.2]octan-2-ones by methanolysis in the presence of CH(3)ONa/La(OTf)(3). Under the given conditions, epimerization at C(6) of the latter led in the least favorable cases only to traces of the more stable 6-endo-hydroxybicyclo[2.2.2]octan-2-ones. This procedure, when combined with the described conversion of easily available 6-endo-hydroxybicyclo[2.2.2]octan-2-ones into the corresponding 6-exo-acetoxy derivatives, provides a convenient route to elusive 6-exo-hydroxybicyclo[2.2.2]octan-2-ones. Applications to total synthesis are shown and envisaged.