Study of the inversion reaction of the lactonic fusion on eremanthine derivatives

Abstract

As α-metileno-γ-lactonas 4(15)-diidroeremantina (8), 4(15),9(10)-tetraidroeremantina (9), isoeremantina (10), acetato alílico Δ 1,10 (11), 1(R),10(R)-diidromiqueliolido (12) e 4α-hidróxi acetato alílico Δ 1,10 (13) foram sintetizadas a partir do produto natural abundante eremantina (1). Essas substâncias foram submetidas à reação de hidrólise com KOH aquoso e os sais carboxílicos dessas lactonas tiveram suas hidroxilas ativadas na posição C-6, pela formação dos respectivos mesilatos (MsCl, Et 3 N, THF ou DMSO) para deslocamento nucleofílico efetuado pelo grupo carboxilato. A utilidade dessa metodologia foi investigada para a obtenção de guaianolidos com fusão lactônica cis na posição C6-C7 e para sintetizar um precursor para estudo posterior da transformação biomimética de guaianolidos em pseudoguaianolidos.The α-methylene-γ-lactones 4(15)-dihydroeremanthine (8), 4(15),9(10)-tetrahydroeremanthine (9), isoeremanthine (10), allylic acetate Δ 1,10 (11), 1(R),10(R)-dihydromicheliolide (12) and 4α-hydroxy allylic acetate Δ 1,10 (13) were synthesized from the abundant natural product eremanthine (1). These substances were submitted to hydrolysis reaction with aqueous KOH and the carboxylic salts of these lactones had their hydroxy groups activated at the C-6 position by formation of respective mesylates (MsCl, Et 3 N, THF or DMSO) which underwent further displacement by carboxylate group. The utility of this methodology was investigated in order to obtain guaianolides with cis lactonic fusion at the C6-C7 position and to synthesize a precursor for posterior study of the biomimetic transformation of guaianolides into pseudoguaianolides.

A Review on the Chemistry of Eremanthine: A Sesquiterpene Lactone with Relevant Biological Activity

“…There was also studied the synthesis of micheliolide, a naturally occurring substance initially isolated from Michelia compressa with relevant biological activity [165]. In the following subitems are described the sequences of reactions that were developed aiming to attain these objectives [150,[166][167][168][169][170] as well as the results of the study from the reactions of catalytic hydrogenation and methanol addition to α-methylene-γ-lactone of eremanthine derivatives [171]. 6.11.1.…”

“…On the other hand, treatment of iodohydrin 139 with MsCl and Et 3 N in dichloromethane, by the procedure of Crossland and Servis [173], generated a mixture of conjugate dienes 151 and 152 instead of the intermediate mesylate at C-9 position (150), which would be used in the next step of hydrogenolysis with NaBH 3 CN in HMPA by the procedure of Hutchins et al [174], aiming to obtain the target molecule 149. The author is disregarding in this review the preliminary results reported before about this reaction [166]. On that occasion this reaction was described in the following way: treatment of 139 with MsCl/Et 3 N/CH 2 b [170] c [171] g [171] c [171] a [170] c [171] e [168,169] d [170] f [168,169] is instantly converted to the final products of elimination (151 and 152).…”

“…The author is disregarding in this review the preliminary results reported before about this reaction [166]. On that occasion this reaction was described in the following way: treatment of 139 with MsCl/Et 3 N/CH 2 b [170] c [171] g [171] c [171] a [170] c [171] e [168,169] d [170] f [168,169] is instantly converted to the final products of elimination (151 and 152). Therefore, the subsequent and unnecessary step of reduction with NaBH 3 CN was not performed on that occasion of his academic formation (M.S.).…”

“…The inversion of configuration at C-6 position on eremanthine derivatives was studied with the substrates 85, 130, 154, and 156-158 shown in Scheme 39. These substances were prepared from eremanthine (1) by simple standard procedures and were described in recent articles [168][169][170]. After exposure of these substrates to reaction conditions of inversion of the lactonic fusion, epimeric mixtures at C-6 were obtained in different proportions (Scheme 39).…”

“…The variations in the proportions of products with cis lactonic fusion obtained in that work were attributed to steric effects at the hydroazulene system. A detailed discussion on the probable causes of variation in the proportions of products with cis lactonic fusion displayed in Scheme 39 was reported in a recent article and in its supplementary information [170]. The author would like to make a correction on the major product of the inversion reaction of lactonic fusion of the allylic acetate 156 (Scheme 39) previsously described in a congress abstract [167].…”