Dataset Information

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens.

ABSTRACT: Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 ?g/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from 1H NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.

SUBMITTER: Molina-Salinas GM

PROVIDER: S-EPMC3600946 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens.

Molina-Salinas Gloria M GM Rivas-Galindo Verónica M VM Said-Fernández Salvador S Lankin David C DC Muñoz Marcelo A MA Joseph-Nathan Pedro P Pauli Guido F GF Waksman Noemí N

Journal of natural products 20110822 9

Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 μg/mL. Stereo ...[more]

PMID: 21859082

Similar Datasets

Project description:A stereogenic center, placed at an exocyclic location next to a chiral carbon in a ring to which it is attached, is a ubiquitous structural motif seen in many bioactive natural products, including di- and triterpenes and steroids. Installation of these centers has been a long-standing problem in organic chemistry. Few classes of compounds illustrate this problem better than serrulatanes and amphilectanes, which carry multiple methyl-bearing exocyclic chiral centers. Nickel-catalyzed asymmetric hydrovinylation (AHV) of vinylarenes and 1,3-dienes such as 1-vinylcycloalkenes provides an exceptionally facile way of introducing these chiral centers. This Article documents our efforts to demonstrate the generality of AHV to access not only the natural products but also their various diastereoisomeric derivatives. Key to success here is the availability of highly tunable phosphoramidite Ni(II) complexes useful for overcoming the inherent selectivity of the chiral intermediates. The yields for hydrovinylation (HV) reactions are excellent, and selectivities are in the range of 92-99% for the desired isomers. Discovery of novel, configurationally fluxional, yet sterically less demanding 2,2'-biphenol-derived phosphoramidite Ni complexes (fully characterized by X-ray) turned out to be critical for success in several HV reactions. We also report a less spectacular yet equally important role of solvents in a metal-ammonia reduction for the installation of a key benzylic chiral center. Starting with simple oxygenated styrene derivatives, we iteratively install the various exocyclic chiral centers present in typical serrulatane [e.g., a (+)- p-benzoquinone natural product, elisabethadione, nor-elisabethadione, helioporin D, a known advanced intermediate for the synthesis of colombiasin and elisapterosin] and amphilectane [e.g., A-F, G-J, and K,L pseudopterosins] derivatives. A concise table showing various synthetic approaches to these molecules is included in the Supporting Information. Our attempts to synthesize a hitherto elusive target, elisabethin A, led to a stereoselective, biomimetic route to pseudopterosin A-F aglycones.

Project description:BackgroundTo inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB.Methods and findingsIn this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence).ConclusionsAmong TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Dataset Information

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens.

Publications

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets