New Insights into the Chemical Composition of Ayahuasca.

Ayahuasca is a psychedelic beverage originally from the Amazon rainforest used in different shamanic settings for medicinal, spiritual, and cultural purposes. It is prepared by boiling in water an admixture of the Amazonian vine Banisteriopsis caapi, which is a source of ß-carboline alkaloids, with plants containing N,N-dimethyltryptamine, usually Psychotria viridis. While previous studies have focused on the detection and quantification of the alkaloids present in the drink, less attention has been given to other nonalkaloid components or the composition of the solids suspended in the beverage, which may also affect its psychoactive properties. In this study, we used nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to study the composition of ayahuasca samples, to determine their alkaloid qualitative and quantitative profiles, as well as other major soluble and nonsoluble components. For the first time, fructose was detected as a major component of the samples, while harmine (a ß-carboline previously described as an abundant alkaloid in ayahuasca) was found to be present in the solids suspended in the beverage. In addition, N,N-dimethyltryptamine (DMT), harmine, tetrahydroharmine, harmaline, and harmol were identified as the major alkaloids present in extracts of all samples. Finally, a novel, easy, and fast method using quantitative NMR was developed and validated to simultaneously quantify the content of these alkaloids found in each ayahuasca sample.

Efficient Access to the Iboga Skeleton: Optimized Procedure to Obtain Voacangine from Voacanga africana Root Bark.

Iboga alkaloids are a group of monoterpenoid indole alkaloids with promising and intriguing biological activities. Ibogaine is the representative member of the series and has become widely known as a potent atypical psychedelic with promising effects to treat substance use disorder. Nowadays, an efficient and scalable enantioselective total synthesis of ibogaine and related iboga alkaloids is still lacking, so direct extraction from natural sources or semi-synthetic schemes are the methods of choice to obtain them in a preparative scale. In particular, ibogaine can be obtained either by a low yielding direct isolation from Tabernanthe iboga or using a semi-synthetic procedure from voacangine, an iboga alkaloid occurring in a higher yield in the root bark of Voacanga africana. In this work, we describe an optimized process to obtain voacangine from V. africana root bark as a precursor of the iboga scaffold. Using a direct acetone-based extraction procedure (0.5 kg of root bark), voacangine was isolated in ∼0.8% of root bark dried weight, while the major alkaloids isolated from the bark were identified as iboga-vobasinyl dimers (∼3.7%) such as voacamine and voacamidine. Since these alkaloids contain the voacangine moiety in their structure, the cleavage of the dimers was further optimized, affording an extra amount of voacangine in ∼50% isolated molar yield. In this manner, the total amount of voacangine obtained by application of the whole procedure to the plant material (extraction and dimer cleavage) could almost duplicate the content originally found in the root bark.

Chemoenzymatic synthesis of trans-tetrahydrofuran cores of annonaceous acetogenins from bromobenzene.

Two types of trans-THF cores, present in acetogenins, have been synthesized by an intramolecular iodoetherification reaction. The starting alkenol was obtained in a few steps from a chiral cis-diol resulting from microbial oxidation of bromobenzene. The cyclization gave complete stereoselectivity for trans-THF cores with either (S,S) or (R,R) configurations at the THF chiral carbons.