Uma metodologia eficiente para a sintese de isotiocianoterpenos

AUTOR(ES)
DATA DE PUBLICAÇÃO

1995

RESUMO

With the purpose of providing an efficient methodology to obtain terpenes containing nitrogen atoms and particularly the isothiocyanosesquiterpenes, bioactive metabolites from marine organisms, we have tested several approaches. The main policy in the present work was directed by the observation that to obtain the tertiary isothiocyanosesquiterpenes the functionalization of terpene skeletons either abundant in nature or readily available intermediates were to be used as substrates. This idea relies on the fact that this work was to not to waste any time on long strategics to build terpene skeletons but to focus on the final step, i.e. introduction of tertiary isothiocyano or nitrogen groups starting from double bonds or ketones, which are wide spread functional groups in natural terpenes and readily available terpene intermediates. Our first attempts were mere adaptations of known methodologies and the results were rather disappointing requiring multiple steps and with final low yiels. As a final resort we have tried the direct introduction of a nitrogen function using thc HSCN addition to double bonds. This methodology was explored from the mechanistic point of view but never applied to the syntheses of natural isothiocyanoterpenes. The in situ, generated HSCN was first added to the monoterpenes (+)-limonene 69, dihydrolimonene 72 and (- )-terpineol 63 leading to the production of R-1- methyl.4-(1-isothiocyano-1-methylethyl)-1-cyclohexene 70 e R-1-methyl-4-(1-methylethyl- 1-thiocyano)-1-cyclohexene 71; 1-isothiocyano-1-methyl-4-isopropyl-cyclohexane 73a(cis), 73b(trans) and 1-methyl-1-thiocyano-4-isopropyl-cyclohexane 74a(cis), 74b(trans); 2-(4- isothiocyano-4-methyl-3-cyclohexyl)-isopropanol 75a(cis), 75b(trans) e 2-(4-methyl-4- thiocyano-3-cyclohexyl)-isopropanol 76a (cis) and 76b (trans) regio and chemioselectively. This methodology was further tested with the sesquiterpene (±)-g2- cadinene 32 producing the (±)-1a-isothiocyano-6-cadinene 30a, (+)-1 b- isothiocyano-6-cadinene 30b, (±)-1 a-thiocyano-6-cadinene 77a and (±)-1 b-thiocyano -6-cadinene 77b. The HSCN addition to (±)-1b-hydroxy-6 cadinene 54a was regioseletive and only (±)-1b-hydroxy-6a-thiocyano-cadinane 78a and (±)-1b-hydroxy-6b- thiocyano-cadinane 78b were produced revealing a hydroxyl participation in the addition process. A regio and stereoselective addition was observed for the reaction with (-)-alloaromadendrene 28 and (+)-aromadendrene 29 lcading to the exclusive isolation of the (-)-10(S)-isothiocyanoalloaromadendrane 79a, diastereomer of the natural product 10a-isothiocyanoalloaromadendrane 26 and the (-)-10(R)-isothiocyanoaromadendrane 27, epipolasina B 82 enantiomer. These allow the final conclusion that we have revealed an efficient methodology to obtain isothiocyanosesquiterpenes isolated from marine organisms.

ASSUNTO(S)

terpenios - sintese sesquiterpenos

ACESSO AO ARTIGO

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