New triterpene and antibacterial labdenoic acid derivatives from Moldenhawera nutans

Abstract

Um novo triterpeno (22β-hidroxilupeol) foi isolado do extrato em metanol do caule de Moldenhawera nutans (Leguminosae) além de diterpenos derivados do ácido labdenóico de ocorrência comum nesta espécie. A partir do ácido labd-8(17)-en-15-óico foram preparados derivados com atividade in vitro discreta frente à Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella cholerasuis e Vibrio parahaemolyticus.A new triterpene derivative (22β-hydroxylupeol) was isolated from the MeOH extract of stems of Moldenhawera nutans (Leguminosae) together with labdenoic acid derivatives of common occurrence in this species. From the labd-8(17)-en-15-oic acid were prepared simple derivatives, which exhibited in vitro weak activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella cholerasuis, and Vibrio parahaemolyticus. Keywords: Moldenhawera nutans, Leguminosae, antibacterial labdene derivatives, 22β-hydroxylupeol IntroductionGenus Moldenhawera Schrard. (Leguminosae: Caesalpinoideae), endemic to Northeast Brazil, is represented by approximately ten species. 1 Previous phytochemical study of M. nutans resulted in the isolation of four known labdene diterpenes besides a new bisditerpene named moldenin. 2 The present work describes the results of the fractionation of the hexane phase obtained from the MeOH extract of M. nutans. Besides the known diterpenes previously isolated, it was also obtained the 3-oxo-labd-8(17)-en-15-oic acid (1) as a methyl derivative (1a), and three triterpenes, lupeol, betulin, and the new lupane derivative (2). The labd-8(17)-en-15-oic acid (3) was the predominant compound in this extract. From this compound, derivatives (4-8) were prepared and some of them were submitted to in vitro antibacterial assays. Results and DiscussionThe structural elucidation of 1a (Figure 1) insignificant effect observed at C-19 in the NMR spectra of 2a together with the coupling constants observed in the 1 H NMR suggested that the hydroxyl group is in equatorial position. The 1 HNMR nOe difference spectra of this compound permitted to corroborate the proposition. When the H-22 was irradiated it was possible to assign increments in Hα-21 (25%), H-29 (3%) and, H-19 (10%). These findings are indicative that all the affected protons were in the same plane. The fragmentation pattern observed in the MS of 2 was also indicative of a hydroxyl group in C-22 of the cyclopentyl ring, especially by mass fragments of 2 at m/z 374 and 2a at m/z 458 ( Figure 2). Since labd-8(17)-en-15-oic acid (3) showed antibacterial activity ( Table 2), some of its simple chemical derivatives were prepared and also evaluated. Derivative 3 was refluxed with MeOH/HCl to obtain the isomeric methyl esters 4a and 5. Next, 4a was submitted to allylic oxidation by t-butyl chromate 6 and furnished 6a. It was also prepared the epoxy derivatives 7a and 8a from 4a by reaction with MCPBA. The derivatives 7a and 8a are new and they were characterized by spectrometric analyses data. Compounds 1a, 2, 4a, and 6a-8a w...

Cistus ladanifer L. Shrub is Rich in Saturated and Branched Chain Fatty Acids and their Concentration Increases in the Mediterranean Dry Season

“…The presence of labdane diterpenes in C. ladanifer leaves and essential oil have been already reported by several authors [12,29,30] and some labdanes have been shown to present antimicrobial, cytotoxic and antitumor activities [31]. The methyl labdenoates detected in our samples have been identified by others after acidic methylation of plant extracts [25,30,32]. Therefore, because we also used acidic methylation for the preparation of FAME, these methyl labdenoates could have also been produced from labdenoic acids present in the plant.…”

“…In addition, peak 1 showed the base peak at m/z 191 formed by cleavage of the C9-C11 bond, as a result it was identified as the methyl labd-8-enoate. This compound had been previously characterized by Domenech-Carbo et al [24] and David et al [25]. According to Enzell and Ryhage [23], a characteristic fragmentation of labdanes having a C8-C17 double bond is the cleavage of the allylic C6-C7 and C9-C10 bonds accompanied by hydrogen transfer producing an intense ion at m/z 137, which was detected in mass spectrum of peak 2 (Fig.…”

Absolute Configuration of (13R)- and (13S)-Labdane Diterpenes Coexisting in Ageratina jocotepecana

“…In turn, the stereochemical scenario for methyl (−)-(5 S ,9 S ,10 S ,13 S )-labd-7-en-15-oate ( 2 ) was comparable to that for 1 . Although this is the first time that ester 2 has been obtained as a natural product, the compound has been prepared previously by treatment of 1 with diazomethane, ,, by dehydration of methyl labdanolate, and by isomerization and methylation of labd-8(17)-en-15-oic acid . However, the C-13 configuration remained undetermined in all these studies.…”

“…The chemical study of the flowers and leaves of A. jocotepecana afforded four diterpenoids (Figure ), namely, (−)-(5 S ,9 S ,10 S ,13 S )-labd-7-en-15-oic acid ( 1 ), methyl (−)-(5 S ,9 S ,10 S ,13 S )-labd-7-en-15-oate ( 2 ), (+)-(5 S ,8 R ,9 R ,10 S ,13 R )-8-hydroxylabdan-15-oic acid ( 3 ), and (−)-(5 S ,9 S ,10 S ,13 Z )-labda-7,13-dien-15-oic acid ( 5 ), whose identity was established by comparison of the experimental spectroscopic data with literature values. − The presence of (13 S )- 1 and (13 S )- 2 , together with (13 R )- 3 in the same species, was unexpected and encouraged a detailed stereochemical study to discern if either the plant possesses the capability for synthesizing both epimers or there was an inconsistency in the previous stereochemical assignments of 1 – 3 .…”

Cardiovascular effects of a labdenic diterpene isolated fromMoldenhawera nutansin conscious, spontaneously hypertensive rats

“…However, the former phytochemical study with the stems of this species was initiated to investigate the compounds responsible for the activity exhibited by an organic extract in the HIV-1 RT Assay (Roche, New York, NY) and the isolation and identification of a new dimeric diterpene were reported (David et al, 1998). Acid labdenic diterpenes from the ent-labdane class were previously described in the methanolic extract of M. nutans (David et al, 2007). The major labdenic diterpene found in this methanolic extract is labd-8(17)-en-15-oic acid (labd-8; Figure 1).…”