Pablo J. Linares-Palomino

Chlorosulfonic acid as a convenient electrophilic olefin cyclization agent

Among several sulfonic acids studied (MeSO3H, p-TsOH, H2SO4, ClSO3H, FSO3H), the scarcely used chlorosulfonic acid showed to be an efficient agent for electrophilic olefin cyclizations with internal nucleophilic termination, in a similar manner that is well-established with fluorosulfonic acid. Its availability, lower price and relatively lesser handling problems makes ClSO3H an advantageous cyclizing agent particularly for high-scale applications. The stereochemical outcome of these cyclizations has been rationalized.

Cinnamtannin B-1 from bay wood exhibits antiapoptotic effects in human platelets

Proanthocyanidins, such as cinnamtannin B-1, are polyphenolic compounds with antioxidant activity that induce apoptosis in a number of tumoral cells. We have now investigated the pro- or anti-apoptotic effects of cinnamtannin B-1 in human platelets. Platelet stimulation with thrombin induced cellular apoptosis, as detected by phosphatidylserine exposure and the activation of caspases-3 and -9. Pretreatment for 30 min with cinnamtannin B-1 impaired thrombin-induced apoptosis in platelets. Thrombin has been shown to induce H2O2 generation in platelets, which induced similar apoptotic events than thrombin in these cells. Pretreatment with cinnamtannin B-1 reduced H2O2-induced phosphatidylserine exposure and caspase activation. Finally, platelet stimulation with thrombin induced translocation of caspases-3 and -9 to the cytoskeletal (Triton-insoluble) fraction, which is important for their activation and the development of apoptotic events. Pretreatment with cinnamtannin B-1 impaired translocation of caspases-3 and -9 to the cytoskeleton and, as a result, procaspases are accumulated in the Triton-soluble fraction. Our results provide evidence for the antiapoptotic actions of cinnamtannin B-1 in human platelets.

Antioxidant activity and free radical‐scavenging capacity of a selection of wild‐growing Colombian plants

BACKGROUND The replacement of some synthetic food antioxidants by safe natural antioxidants has fostered research on the screening of raw materials to find new vegetable sources of antioxidants. In this study the antioxidant activity of eight wild-growing Colombian plants was assessed by four complementary assays. RESULTS An evaluation of the antioxidant activity of ten ethanolic extracts from Baccharis chilco, Cinnamomum triplinerve, Ilex laurina, Lachemilla orbiculata, Lepechinia conferta, Quercus humboldtii, Rubus urticifolius and Tephrosia cinerea was carried out. Furthermore, the total phenolic content was determined by the Folin-Ciocalteu method, and the relationship between phenolic content and activity was also statistically investigated. Cinnamomum triplinerve, L. conferta and I. laurina were found to have the highest phenolic contents. Baccharis chilco, C. triplinerve, I. laurina, L. conferta, Q. humboldtii and R. urticifolius showed higher radical-scavenging activity (DPPH and superoxide assays) than commercial rosemary oleoresin (reference). Lachemilla orbiculata and R. urticifolius showed higher antioxidant activity (β-carotene-bleaching test) than the reference. The protection factor of all studied plant extracts was below that of the reference according to the Rancimat test. CONCLUSION On the basis of the results obtained, C. triplinerve, Q. humboldtii and R. urticifolius seem to be the most promising species for further investigation in order to identify the compounds responsible for their activity.

Synthesis and evaluation of the platelet antiaggregant properties of phenolic antioxidants structurally related to rosmarinic acid

Polyphenols, such as rosmarinic acid, are widely distributed natural products with relevant antioxidant activity. Oxidative stress plays an important role in the pathogenesis of a number of disorders. Here, we report on the synthesis and biological effects of the polyphenolic esters hydroxytyrosyl gallate (1), hydroxytyrosyl protocatechuate (2) and hydroxytyrosyl caffeate (3), structurally related to rosmarinic acid. The three compounds showed a greater free radical scavenging activity than their precursors and also than rosmarinic acid. Esters 1 and 3 significantly reduced thrombin-evoked platelet aggregation, which is likely mediated to the attenuation of thrombin-stimulated Ca(2+) release and entry. The three compounds reduced the ability of platelets to accumulate Ca(2+) in the intracellular stores, probably by enhancing the Ca(2+) leakage rate and reduced store-operated Ca(2+) entry in these cells. These observations suggest that the structurally-simplified analogs to rosmarinic acid, compounds 1 and 3, might be the base of therapeutic strategies to prevent thrombotic complications associated to platelet hyperaggregability due to oxidative stress.

On‐Line Activity Screening for Radical Scavengers from Baccharis chilco

Baccharis plants have been used since ancient times in American traditional medicine. Baccharis chilco is a perennial shrub of temperate regions of South America that grows well in rainfall forests of Colombia. Neither chemical composition nor biological studies of this plant have ever been reported. Two caffeoylquinic acid (CQA) derivatives, 5‐O‐[(E)‐caffeoyl]quinic acid (1) and 3,5‐di‐O‐[(E)‐caffeoyl]quinic acid (3), and rosmarinic acid (2) have been isolated from B. chilco growing wild in Colombia, using the on‐line HPLC‐DAD‐DPPH radical‐scavenging detection technique as guidance. In the course of the purification work, L‐chiro‐inositol (4) was also isolated. Structures of the four isolated compounds were determined by spectroscopic methods. Antioxidants 2 and 3 exhibited high antiradical activities evaluated by the 2,2‐diphenyl‐1‐picrylhydrazyl radical (DPPH.) assay, although somewhat lower than that of the reference compound ascorbic acid. The on‐line HPLC‐DAD‐DPPH technique allowed a rapid pinpointing of antioxidants in the studied EtOH extract, and the facile guided isolation of the target molecules.

Synthesis and Olfactory Evaluation of Bulky Moiety-Modified Analogues to the Sandalwood Odorant Polysantol®

Five new bulky moiety-modified analogues of the sandalwood odorant Polysantol® have been synthesized by aldol condensation of appropriate aldehydes with butanone, deconjugative α-methylation of the resulting α,β-unsaturated ketones, and reduction of the corresponding β,γ-unsaturated ketones. The final compounds were evaluated organoleptically and one of them seemed to be of special interest for its natural sandalwood scent.

3-Methyl-3-(6,6,6a-trimethyl-hexahydro-cyclopenta[b]furan-2-yl)-butan-2-one

A 40% aqueous solution of sulfuric acid (0.5 mL) was added to a stirred solution of 3,3-dimethyl- 4-hydroxy-5-(2,2,3-trimethyl-3-cyclopentenyl)-pentan-2-one (1) (630 mg, 2.65 mmol) in methanol (5 mL) and the mixture refluxed for 1.5 h.[...]

Synthesis of cassane-type diterpenes from abietane compounds: the first synthesis of taepeenin F

The first synthesis of the aromatic cassane-type diterpene taepeenin F from abietic acid is reported. The key steps of the synthetic sequence are the ipso-substitution of the isopropyl group of a dehydroabietane derivative by a formyl group, after treatment with Cl2CHOMe and AlCl3, and the oxidative cleavage of a dihydronaphthalene intermediate. The deisopropylation reaction of dehydroabietane derivatives is revised and a complementary study on this subject is included. A mechanism for this reaction is postulated.

(Z)-2-Methyl-3-(1-phenyl-ethylamino)-but-2-enoic acid ethyl ester

p-Toluenesulfonic acid (48 mg, 0.25 mmol) was added to a stirred mixture of ethyl 2-methyl-acetoacetate (1) (346 mg, 2.40 mmol) and a-methylbenzylamine (2) (358 mg, 2.95 mmol) in toluene (13 mL) [1].[...]

5-Hydroxy-2-methyl-3-oxo-6-(2,2,3-trimethyl-cyclopent-3-enyl)-hexanoic acid ethyl ester

Sodium (241 mg, 10.48 mmol) was added to absolute ethanol (40 mL) and the mixture refluxed until sodium reacted completely.