A rhodium-catalyzed C-H activation/cyclization approach toward the total syntheses of cassiarin C and 8-O-methylcassiarin A from a common intermediate.

Three short and efficient total syntheses of cassiarin C are reported, from a chromanone common key intermediate. A C-H activation strategy, under rhodium catalysis on its pivaloyl oxime, enabled the installation of the pyridine ring. Dehydrogenation of 8-O-methylcassiarin C afforded 8-O-methylcassiarin A. A kinetic experiment and DFT calculations of the intermediates helped to gain insight into the unusual site- and stereo-specific H/D exchange of cassiarin C in CD3OD.

Total Synthesis of Aqabamycin G, a Nitrophenyl Indolylmaleimide Marine Alkaloid from Vibrio sp. WMBA.

The first total synthesis of the marine alkaloid aqabamycin G is disclosed. The synthetic sequence involved the stepwise addition to maleimide of an indole motif and a substituted diazo-benzenoid unit derived from acetaminophen. An alternative strategy using a protected phenol is also reported.

Evolution of the Synthesis of Remdesivir. Classical Approaches and Most Recent Advances.

The broad-spectrum antiviral Remdesivir, a monophosphate nucleoside analogue prodrug (ProTide), was repurposed. In May 2020, it received emergency approval by the FDA, being the first drug approved to fight the new coronavirus (COVID-19) disease which targets the virus directly. The main synthetic strategies toward Remdesivir, and their relevant modifications, are presented and discussed, to provide a panoramic view of the state-of-the-art and the more important advances in this field. Recent progress, proposed improvements, and uses of novel technologies for the synthetic sequence are also detailed.

First total synthesis of ampullosine, a unique isoquinoline alkaloid isolated from Sepedonium ampullosporum, and of the related permethylampullosine.

A straightforward and convenient approach toward the first total synthesis of ampullosine, a structurally unique 3-methylisoquinoline alkaloid isolated from Sepedonium ampullosporum, is reported. Access to the related O-methyl ampullosine methyl ester from a common intermediate is also disclosed. The synthetic sequence toward the natural product comprised a Kolbe-type carboxylation of 3,5-dihydroxybenzoic acid and further esterification of the diacid, followed by masking of one of the phenols through selective ester reduction and subsequent acetonide formation. Installation of the three-carbon atom required for the 3-methylpyridine ring was performed by triflation of the remaining free phenol and a Pd-catalyzed Suzuki-Miyaura reaction with potassium E-propenyltrifluoroborate. Deprotection of the acetonide, followed by partial oxidation of the benzylic alcohol to the salicylaldehyde, O-methylation of the free phenol and hydrazonation of the resulting ortho-anisaldehyde derivative gave a hydrazone-based 1-azatriene. This was further subjected to 6π-azaelectrocyclization to afford permethylampullosine (11 steps, 14% overall yield), whereas exhaustive demethylation with AlI3 generated in situ gave ampullosine (12 steps, 3.2% global yield).

The 6π-azaelectrocyclization of azatrienes. Synthetic applications in natural products, bioactive heterocycles, and related fields.

Covering: 2006 to 2018 The application of the 6π-azaelectrocyclization of azatrienes as a key strategy for the synthesis of natural products, their analogs and related bioactive or biomedically-relevant compounds (from 2006 to date) is comprehensively reviewed. Details about reaction optimization studies, relevant reaction mechanisms and conditions are also discussed.