Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).

Practical and scalable synthesis of beclomethasone dipropionate.

Beclomethasone dipropionate (1) is a synthetic corticosteroid with anti-inflammatory, antipruritic, and anti-allergy properties. It is widely used to treat asthma, allergic rhinitis, and dermatoses. However, existing synthetic routes to this active pharmaceutical ingredient (API) contain steps resulting in low and/or inconsistent yields, and use obsolete reagents. Such inconsistencies coupled with a lack of reliable experimental data makes laboratory-scale and large-scale synthesis of this API difficult and time-consuming. In this paper, we report a practical and scalable approach to synthesize 1 from the readily available steroidal intermediate, 16ß-methyl epoxide (3, DB-11). A gram-scale to kilogram-scale synthesis of 1 was achieved with 82% yield, using a cost-effective and scalable methodology. Selective propionylation of the hydroxyl groups at C17 and C21 demonstrate the fact that this approach can be conveniently implemented in fine chemical industries.

Updating Levothyroxine Synthesis for the Modern Age.

Synthesis of levothyroxine sodium, the sodium salt of a synthetic levoisomer of thyroxine, revolutionized the management of hypothyroidism and related symptoms. However, the primary synthetic route to this active pharmaceutical ingredient (API) is more than 70+ years old with low-yielding steps and obsolete reagents. It lacks experimental data on intermediates, making laboratory and large-scale synthesis of this API difficult and time-consuming. Here, we describe an improved synthesis of levothyroxine using commonly available modern reagents. By modifying and replacing low yielding and/or unproductive steps of Chalmers synthesis, we were able to achieve higher overall yields (39-51%) consistently. Key modifications include an alternative path to the selective N-acetylation step that yielded 5 in a pure and consistent fashion. Our improved methodology, coupled with detailed experimental data, provides a practical alternative to existing methods that can be conveniently implemented to synthesize Levothyroxine sodium in fine chemical settings.

An efficient and high-yielding method for extraction and purification of linamarin from Cassava; in vitro biological evaluation.

During the last three decades, studies of linamarin extracted from cassava have received increased attention due to the presence of high cyanogenic compounds in these extracts. The methods that are utilized to isolate linamarin are either tedious or use acidic conditions resulting in poor yields. In this study, a novel cryocooled method of extraction has been developed to isolate linamarin from Cassava root peel. Approximately 18 g of linamarin was isolated from 1 kg of fresh Cassava root peel, which is the highest amount reported to date. Linamarin was fully characterized using NMR, IR and LCMS. The anti-cancer properties of pure linamarin and Cassava crude extract were evaluated by a comprehensive cytotoxic assay, using MCF-7, HepG2, NCI H-292, AN3CA and MRC-5 cell lines. The crude extract showed higher cytotoxicity compared to pure linamarin. The results of the biological evaluation are comparable to other reported studies in the literature.