Two New Cytotoxic Clerodane Diterpenoids from Casearia membranacea

Abstract

Clerodanes are a group of novel diterpenoids with interesting biological effects such as antitumor-related activities. [1][2][3][4][5] Casearia membranacea HANCE (Flacourtiaceae) is the only species that belongs to the genus Casearia in Taiwan. 6) During the course of searching for novel antitumor agents from the terrestrial plants in Taiwan,[7][8][9] an ethanolic extract of the leaves and twigs of C. membranacea collected in Ken-ting showed significant cytotoxicity against the human prostate tumor cells (PC-3). To explore the origin of biological activity, bioassay-guided fractionation of the extract of the leaves and twigs of this species has resulted in the isolation of two new clerodane diterpenes, designated as caseamenbrols A (1) and B (2), together with the known casearlucin A (3). Herein, we wish to report the isolation, structural elucidation and cytotoxicity of these novel compounds. Results and DiscussionThe ethanolic extract of C. membranacea was fractionated by repeated column (Si gel and Sephadex LH-20) chromatography and preparative TLC to furnish caseamenbrols A (1, 0.012%) and B (2, 0.024%) in addition to casearlucin A (0.0023%).10)The FAB-MS and 13 C-NMR spectra of 1 revealed its molecular weight as 518 and molecular formula C 29 H 42 O 8 . The UV spectrum showed absorption due to conjugated diene at l 225 nm. The IR spectrum displayed absorption bands specific for a hydroxyl group (3445 cm -6). Taking into account three olefinic bonds and three ester carbonyls, the presence of three rings is justified to satisfy nine degrees of unsaturation. The spectral data of 1 are in conformity with the basic skeleton of clerodane diterpenes previously isolated from Casearia. 11,12) The presence of a six-carbon diene side chain at C-9 was confirmed by the long range correlations between H-12/C-9; H-14/C-12, C-13, C-16; H-15/C-13/C-14, C-16. In addition to casearlucin A (3), two new clerodane diterpenes, caseamembrols A (1) and B (2) have been isolated from the leaves and twigs of Casearia membranacea by bioassay-guided fractionation. The structures of the new compounds were established on the basis of extensive 1D-and 2D-NMR spectroscopic analysis. Compounds 1-3 exhibited significant cytotoxicity against human prostate (PC-3) cancer cells.

New clerodane diterpenoids from Laetia procera (Poepp.) Eichler (Flacourtiaceae), with antiplasmodial and antileishmanial activities

“…Further fractionation by successive flash chromatography on silica gel led to the isolation of the pure compounds Casearlucine A 1 and Caseamembrol A 2. NMR and mass spectral data of compounds 1 and 2 were identical to those previously reported for Casearlucine A (or Bucidarasin B) and Caseamembrol A, 9,5,10 although compound 2 displayed a significantly higher optical rotation than the value reported for Caseamembrol A (reported for Casearmembrol A: [a] D À8.3°( c 0.38, MeOH), found for 2: [a] D À61°(c 0.40, MeOH)). Laetiaprocerines A-D and Laetianolide A were obtained by further purification on reversed-phase semipreparative HPLC.…”

Contribuição ao estudo dos metabólitos secundários do gênero Casearia e de algumas de suas atividades biológicas

“…O deslocamento químico de C-5 ( 53,3) foi semelhante aos descritos para diterpenos clerodânicos e compostos análogos (ITOKAWA et al, 1990;MORITA et al, 1991;SHEN et al, 2004a). Porém os  e  ou  e , conforme dados da literatura (SHEN et al, 2004a;OBERLIES et al, 2002;GIBBONS et al, 1996).…”

“…Adicionalmente observou-se no espectro dois simpletos em  1,86 (s, COOMe-19) e  2,02 (s, COOMe-18) correspondestes a grupos metilas de acetato (OBERLIES et al, 2002;ITOKAWA et al, 1990;SANTOS et al, 2007). -3 ( 128,6), também característica de diterpenos clerodânicos (OBERLIES et al, 2002;ITOKAWA et al, 1990 CHEN et al, 2008;SHEN et al, 2004a). As correlações observadas no mapa de contornos A estereoquímica relativa dos 8 centros estereogênicos foi determinada a partir dos dados de RMN de 13 C, NOESY 1D e dos valores das constantes de acoplamento 117,Tabela 20).…”

“…O deslocamento químico de C-5 ( 54,3) foi semelhante aos descritos para diterpenos clerodânicos e compostos análogos (ITOKAWA et al, 1990;MORITA et al, 1991;SHEN et al, 2004a) A substância 14 foi submetida a reação de acetilação, resultando em um novo diterpeno clerodânico denominado casearupestrina E (14a …”

“…Em estudo realizado por Mosaddik et al (2007b) (MORITA et al, 1991;SHEN et al, 2005c;SHEN et al, 2004b;SANTOS et al, 2010): a) a presença…”