Two New Sesquiterpene Lactones from the Leaves of Laurus nobilis

Abstract

Laurus nobilis L. (Lauraceae) is an evergreen tree widespread in the Mediterranean area and Europe, and as a folk medicine, the decoction or tea of bay leaves is often used as a carminative, intestinal and gastric antispasmodic, against diarrhea , for rheumatic pains, in diseases of the respiratory tract, as a cough sedative, to treat asthma and cardiac diseases , 1-3) and in cases of dysmenorrhea (pers. comm.). Previous phytochemical investigations have led to the isolation of several classes of secondary metabolites of laurel leaves, particularly sesquiterpene lactones, 4,5) alkaloids, 5,6) monoterpene and germacrane alcohols, 5,7,8) catechin and pro-cyanidine derivatives, 5,9) glycosylated flavonoids, 10) and megastigmane glucosides. 11) As well as sesquiterpene lac-tones, laurenobiolide 12) and costunolide 13) have been identified as the major compounds of L. nobilis. Many of these lactone derivatives have been shown to possess various pharmacological effects, with antimicrobial, 14,15) immuno-modulating 16) and cytotoxic activities. 17) Three costunolide and germacranolide derivatives, isolated from L. nobilis, were recently shown to be able to induce apoptotic chro-matin condensation in leukemia cells (HL-60), 18,19) indicating their possibility as leads in the development of new classes of antileukemic drugs. For this reason, we considered this plant in our ongoing studies on antiproliferative agents from vege-tal sources. Sequential extracts were prepared using solvents in increasing polarity (petroleum ether, chloroform and methanol), and residues were used to perform preliminary cytotoxic tests against two different cell lines. Activity against Jurkart cell line was established in petroleum ether (PEE) and chloroform extracts, with an IC 50 of 9.1 and 10.2 mg/ml respectively. Only PEE was active against LoVo with an IC 50 of 15.1 mg/ml. Fractionation of the extracts led to the isolation of five sesquiterpene lactones, two of which (1, 2) are new natural products. Compound 1 was obtained as colorless needles. The high resolution (HR)-MS [atmospheric pressure ionization-time of flight (API-TOF)] spectrum showed a protonated molecular ion [MH] at m/z 233.1524, corresponding to a molecular formula of C 15 H 20 O 2. The IR spectrum showed the presence of a g-lactone ring (1765 cm 1). The 1 H-NMR spectrum showed two doublets (each, J0.8 Hz) at d 5.33 and 6.10, as-cribable to an exocyclic methylene group, and a broad singlet at d 5.00. Two singlets, each integrating for three protons, were observed at d 1.10 and 1.47, indicating the presence of two methyl groups (Table 1). The 13 C-NMR data revealed the presence of fifteen carbon atoms. Quaternary carbon resonances were obtained by comparison of heteronuclear multiple quantum coherence (HMQC) and 13 C data. A carbonyl function at d C 171.8 and two quaternary olefin carbons at d C 136.8 and 145.9 were observed. Other quaternary resonances were observed at d C 74.2 and 46.8. Six methylene groups were observed in HMQC spectrum, one linked to sp 2 carbon resonanc...

Phytochemicals and Biological Activities of Laurel Tree (Laurus nobilis)

“…The anticancer activities of these extracts have driven the bioactivity-guided isolation of the responsible active compounds. Thus, lauroside B (76), a megastigmane glycoside from a methanolic extract of laurel leaves [211]; kaempferol-3-O-pcoumarate (134), a flavonoid from an ethyl acetate extract of laurel leaves [85]; costunolide (16), santamarine (28), reynosin (31), 11,13-dehydrosantonin (42), gazaniolide (45), spirafolide (48), and lauroxepine (65), sesquiterpenoids from a methanolic extract of laurel fruits [39]; anhydroperoxycostunolide (21) and 3-oxoeudesma-1,4(15),11(13)triene-12,6α-olide (43), sesquiterpenoids from a hot water extract of laurel leaves [94]; dehydrocostus lactone (22) and 3-chlorodehydrocostus lactone (25), sesquiterpenoids from a petroleum ether extract of laurel leaves [50]; costunolide (16), dehydrocostus lactone (22), 3-chlorodehydrocostus lactone (25), and lactone 49, sesquiterpenoids from a chloroform extract of laurel leaves [50,207]; lucentolide (20), anhydroperoxycostunolide (21), santamarine (28), reynosin (31), hydroperoxide-magnolialide (32), magnolialide (35), 3-peroxyarmefolin (36), 11,13dehydrosantonin (42), tubiferin (44), some more eudesmane lactones (30, 33, 34, 37, 38, 47), and several -hydroxyesters (60-64), all sesquiterpenoids from a dichloromethane extract of laurel leaves [52], have been isolated as the active compounds.…”

“…Sesquiterpenoids: It was reported in 1971 [35] the isolation from laurel roots of the first sesquiterpene lactone: laurenobiolide (11). Since then, ten more lactones with a germacrane skeleton (12)(13)(14)(15)(16)(17)(18)(19)(20)(21) have been isolated from roots [36,37], fruits [38,39] and leaves [37,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] (Figure 4). Dehydrocostus lactone (22), zaluzanin D (24) and eremanthin (26) were the first lactones isolated from laurel with a guaiane skeleton [38], and santamarine (28) and reynosin (31) the first ones with a eudesmane skeleton [40].…”

“…More guainolides (23,25,27) and eudesmanolides (29,30,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) were further isolated from both laurel fruits and leaves (Table 1). Lactone spirafolide (48), found in leaves [42,46] and fruits [39], has a rare molecular structure carrying an oxepine ring, and lactone 49 was a new sesquiterpene derivative [50]. Although not everyone agrees [55,56], it is thought that all these -unsaturated--lactones could be behind of some reported allergic contact dermatitis caused by laurel leaves [57].…”

“…In addition to this group of sesquiterpene lactones, which represent a characteristic group of phytochemicals in L. nobilis, other sesquiterpenoids have been isolated from methanol or chloroform extracts of laurel fruits [38,39] and leaves [41][42][43][44]47,[52][53][54] such as compounds 50-72 ( Figure 4). Eleven of all the sesquiterpenoids found in laurel tree were new natural products (25,27,29,49,50,52,58,(65)(66)(67)72) when isolated.…”

Assessment of Volatile Oil Composition, Phenolics and Antioxidant Activity of Bay (Laurus nobilis) Leaf and Usage in Cosmetic Applications

“…Laurus nobilis (Lauraceae), one of the main sources of plant volatile oils, is an evergreen shrub that can grow up to 8 meters tall. It has dark green leaves about 8-14 cm long and 3-4 cm wide [12,13].…”