Artemisinin metabolism by P450 enzymes

Francis Yoshimoto and co-workers taught a biochemistry laboratory course at UTSA in the course based undergraduate research experiences (CUREs) format related to exploring how the plant natural product, artemisinin, is metabolized by human cytochrome P450 enzymes. The manuscript was published in the Journal of Chemical Education.

Journal of Chemical Education paper

Schönecker with a C19-iminopyridine

The Schönecker oxidation popularized in the total synthesis of many natural products involves a copper mediated oxidation of a C17-iminopyridine steroid derivative to yield a 12beta-hydroxy steroid product. Here, a C19-iminopyridine steroid derivative was used to yield some wild chemistry: C1beta-hydroxylation/19-peroxidation and a C5-C6 olefin difunctionalization.

Steroids paper

C2-Olefinated Dihydroartemisinic Acid Analogue Aromatizes

Dihydroartemisinic acid is the biosynthetic precursor to artemisinin, an endoperoxide containing plant natural product used to treat malaria. The research team of Francis Yoshimoto at UTSA and collaborators: Catherine Wakeman’s lab from Texas Tech University and Luis Martinez’s lab from the University of Florida, showed that an olefinated version of dihydroartemisinic acid aromatizes instead of forming an endoperoxide ring revealing new insights towards endoperoxide formation. They applied this knowledge to the biosynthesis of the aromatic ring in serrulatene. Antimicrobial activities were measured against Staphylococcus aureus and Cryptococcus neoformans with some of their synthesized compounds having MIC values of 12.5 micrograms/mL.

Journal of Natural Products paper

Pressures of Academia

We always hear about mental health concerns for our students, but here’s an interesting article reminding us about the mental health of being a faculty.

eLife Sciences paper

Mechanistic insights towards endoperoxide formation of artemisinin

Artemisinin, one of the topics of the Nobel Prizes in Medicine in 2015, and its derivatives have been used to treat malaria. A new study published in the Journal of Natural Products finds that the endoperoxide formation of artemisinin from dihydroartemisinic acid, its biosynthetic precursor, undergoes a mixed mechanism. The study, from the lab of Francis Yoshimoto at UTSA, used regioselectively deuterated dihydroartemisinic acid isotopologues to measure competitive intermolecular kinetic isotope effects in the formation of artemisinin. The supporting information file is over 500 pages!

Cool!


Journal of Natural Products paper

Update – SARS CoV-2 Mutants

Here’s an update related to SARS CoV-2 mutants that are more infective than the original strain. The basis behind more infective strains of SARS CoV-2 seems to be the spike protein, which is the protein the virus uses to enter the human cells.

The Protein Journal

SARS CoV-2 update

Here’s an update on a biochemical perspective of SARS CoV-2 proteins (especially the spike protein).

The Protein Journal

Tryptophan labeling

Michael Taylor and co-workers from the University of Wyoming reported in JACS on a method to label tryptophan residues using an N-carbamoyl pyridinium salt and light.

JACS paper

Zephycarinatines syntheses

Hiroaki Ohno and co-workers at Kyoto University have reported in ACIE on the synthesis of zephycarinatines.

 

ACIE paper

(−)‐Conidiogenone B, (−)‐Conidiogenone, and (−)‐Conidiogenol syntheses

Hongbin Zhai and co-workers from Peking University have reported in ACIE on the synthesis of conidiogenone B, conidiogenone and conidiogenol.

 

ACIE paper