NMR and X-ray studies of apetalic acid isolated from Calophyllum brasiliense and of its chiral amides.

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From: Canadian Journal of Chemistry(Vol. 100, Issue 1)
Publisher: NRC Research Press
Document Type: Report
Length: 5,282 words
Lexile Measure: 1630L

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Abstract :

The tropical tree Calophyllum brasiliense Cambess. (Clusiaceae) grows in rain forests from Brazil to Mexico. Its leaves, as well as those of other Calophyllum species, are rich sources of chromanone acids, such as apetalic acid, isoapetalic acid, and their derivatives. Apetalic acid has shown significant antimycobacterial activity. The biological activity of apetalic acid has been related to the configuration of three asymmetric centers and the stereochemistry of the molecule; however, the C-19 configuration in the acidic side chain has not been fully resolved. For this reason, the unequivocal determination of the absolute configuration by means of X-ray crystallography in a sample of unique homogeneous apetalic acid stereoisomer was the most important point to start this study. Chiral amides were prepared using the carboxyl group. We determined the C-19 stereochemistry of apetalic acid and its specific chiral derivatives using NMR, X-ray diffraction, and molecular mechanics. Finally, we observed that steric hindrance in the side chain of apetalic acid leads to restriction of rotation around the pivotal linkage C-10-C-19, establishing chiral centers at C2(R), C3(S), and C19(R). We were able to separate the derivatives of these two high-rotatory-barrier conformers of apetalic acid by forming diastereoisomeric amides with phenylglycine methyl ester having a chiral center at C-2'. Our results confirmed the existence of atropisomerism in the apetalic acid molecule. Key words: NMR of apetalic acid chiral amides, absolute configuration and conformation, X-ray studies versus NMR, stable conformers of apetalic acid, high-rotatory-barrier conformers of apetalic acid. L'espece Calophyllum brasiliense Cambess. (Clusiaceae) est un arbre qui pousse dans les forets tropicales du Bresil jusqu'au Mexique. Ses feuilles, comme celles d'autres especes de Calophyllum, sont une source riche en acides de chromanone, tels que l'acide apetalique, l'acide isoapetalique et leurs derives. L'acide apetalique a montre une activite antimycobacterienne substantielle. Un lien a ete observe entre l'activite biologique de l'acide apetalique et la configuration de trois centres asymetriques ainsi que la stereochimie de la molecule. Cependant, la configuration du carbone C19 de la chaine laterale acide n'a pas ete completement resolue. Pour cette raison, la determination sans equivoque de la configuration absolue par radiocristallographie sur un echantillon d'un seul stereoisomere homogene d'acide apetalique a ete le motif le plus important pour entreprendre cette etude. Nous avons prepare des amides chiraux en utilisant le groupe carboxyle. Nous avons determine la stereochimie du carbone C19 de l'acide apetalique et de certains de ses derives chiraux au moyen de la RMN, de la diffraction des rayons X et de la mecanique moleculaire. Enfin, nous avons observe que l'encombrement sterique dans la chaine laterale de l'acide apetalique entraine une restriction de rotation autour de la liaison C10-C19, qui determine la stereochimie des centres chiraux aux positions C2(R), C3(S) et C19(R). Nous sommes parvenus a separer les derives de ces deux conformeres a barriere de rotation elevee de l'acide apetalique en formant des amides diastereoisomeriques avec l'ester methylique de la phenylglycine qui possedent un centre chiral a la position C2'. Nos resultats confirment l'existence d'atropisomerisme dans la molecule d'acide apetalique. Mots-cles : RMN d'amides chiraux de l'acide apetalique, configuration absolue et conformation, etudes par rayons X versus RMN, conformeres stables de l'acide apetalique, conformeres a barriere de rotation elevee de l'acide apetalique.

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Gale Document Number: GALE|A689991239