Cembranolides from the Leaves of Croton gratissimus

Abstract

20,10-olide (4a), have been isolated from the leaves of Croton gratissimus. The acetyl derivatives of 8 and 4a were evaluated against a chloroquine-sensitive strain of Plasmodium falciparum (D10).Croton gratissimus Burch. (C. zambesicus Mull. Arg.; C. microbotryus Pax.) (Euphorbiaceae) grows on stony hillsides as a semideciduous tree species throughout much of the warmer and drier regions from South Africa, northeastwards, to the horn of Africa. The leaves of this plant are ground with goat fat and those of two other Croton species, the resulting paste is heated on coals, and the fumes are inhaled as a cure for insomnia. 1 A tea made from the leaves is taken for coughs in Botswana. 2 Watt and Breyer-Brandwijk 3 documented C. gratissimus as a remedy for fever, for treating bleeding gums and eye disorders, and as an ingredient used to "smoke" rheumatic patients. In South Africa, the leaves are dried and smoked for influenza, colds, and fevers. 4 The traditional use of this species for treating fevers, intermittent or otherwise, indicates its likely application as an antimalarial, since it is employed as such within the malaria endemic region of southern Africa. In Nigeria, bark infusions of the species (as C. zambesicus) are reported to treat malaria. 5 Accordingly, crude dichloromethane extracts of South African leaves of C. gratissimus have previously been investigated for antiplasmodial activity in vitro and shown to have an IC 50 value of 3.5 μg/mL; 6 the constituent(s) responsible were not identified. The stem bark of C. gratissimus has been reported to yield four cembranoids, namely, (+)-(1R*,2S*,7S*,8S*,12R*)-7,8-epoxy-2,12-cyclocembra-3E,10Z-dien-20,10-olide, (+)-(1R*,10R*)c e m b r a -2 E , 4 E , 7 E , 1 1 Z -t e t r a e n -2 0 , 1 0 -o l i d e , (+)-(1R*,4S*,10R*)-4-hydroxycembra-2E,7E,11Z-trien-20,10-olide (4a), and (−)-(1R*,4R*,10R*)-4-hydroxycembra-2E,7E,11Z-trien-20,10-olide, in addition to lupeol, 4(15)eudesmene-1β,6α-diol, and α-glutinol.7

Composição química de uma população de Croton gratissimus Burch (Euphorbiaceae)

“…33 Estudos prévios sobre a Croton gratissimus focaram-se sobre as folhas. 3,7 Foram identificadas principalmente cembranolidas, 2,3 trachilobanos e isopimaranos, 6,7 e na casca do caule, da qual foram isolados clerodanos e trachilobanos. 2,6 Este é o primeiro estudo sobre a composição química de flores, caules e folhas da Croton gratissimus.…”

“…encontra-se na África subsariana, crescendo em encostas rochosas das regiões quentes e secas do noroeste da África do Sul até ao Corno de África. 2,3 Todas as partes da C. gratissimus são usadas para fins medicinais. As folhas são aromáticas e frequentemente utilizadas como infusões para tratar a tosse e a febre.…”

“…As combinações da raiz e da casca são usadas para tratar distúrbios respiratórios. 2,4 Estudos anteriores sobre a composição química da C. gratissimus revelaram a presença de cembranolidas, lupeol, α-glutinol e 4(15)-eudesmeno-1β,6α-diol na casca do caule, 2 e cembranolidas, lupeol, α-glutinol e 24-etilcolesta-4,22-dien-3-ona, 3 kaempferol--3-O-β-6''(p-coumaroil) glucopiranosídeo (tilirosida), apigenina-6-C--glucosídeo (isovitexina) e kaempferol 5 …”

Labdane-type diterpenoids from Croton laevigatus

“…The 1 H-1 H COSY experiment showed connectivity of three moieties: I: 1 CH 2 -2 CH 2 -3 CH 2 ; II: 5 CH-6 CH 2 -7 CH 2 ; and III: 9 CH-11 CH(O)-12 CH 2 . The HMBC correlations from CH 3 -19 (d H 0.79, 3H, s) to C-3 (d C 35.1), C-5 (d C 44.4), and C- 18 (d C 15.7); from H [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]each 1H,d,J ¼ 11.2 Hz) to C-3, C-5, and C-19 (d C 17.7); and from H 2 -2 (d H 1.50 and 1.60, each 1H, m) to C-4 (d C 37.5) indicated that C-4 connected units I and II together. The HMBC correlations from CH 3 -20 (d H 0.96, 3H, s) to C-1 (d C 41.4), C-5, and C-9 (d C 66.0) and from H 2 -1b (d H 0.96, 1H, m) to C-9 suggested that C-10 (d C 35.9) connected units I and III together.…”

“…The HMBC correlations from CH 3 -20 (d H 0.96, 3H, s) to C-1 (d C 41.4), C-5, and C-9 (d C 66.0) and from H 2 -1b (d H 0.96, 1H, m) to C-9 suggested that C-10 (d C 35.9) connected units I and III together. Furthermore, the HMBC correlations from H-9 (d H 1.57, 1H, d, J ¼ 2.0 Hz) to C- 17 (d C 78.5),1H,td,J ¼ 5.2,2.4 Hz) and H 2 -6 (d H 1.32 and 1.60, each 1H, m) to C-8 (d C 80.1), and from H [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]each 1H,d,J ¼ 9.6 Hz) to C-7 (d C 33.3), C-9, IR spectrum showed absorption bands for hydroxyl (3422 cm À1 ), ester carbonyl (1735 cm À1 ) and olen (1676 cm À1 ) functionalities. The 1 H and 13 C NMR spectroscopic data (Tables 1 and 2) of 3 resembled those of 1 and 2, sharing the same AB rings, and also belongs to nor-labdane-type diterpene series.…”