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

7,20-Diisocyanoadociane synthesis

Ryan Shenvi and co-workers reported in JACS on the synthesis of 7,20-diisocyanoadociane.

 

JACS paper

(±)-Erythro-7′-methylcarolignan E

Qiong Gu and co-workers from Sun Yat-sen University and UNC have reported in the Journal of Natural Products on the isolation of (±)-erythro-7′-methylcarolignan E with anti-HIV activity.

 

JNP paper

Erinacine S

Chien-Chang Shen and co-workers from Hung Kuang University and National Yang-Ming University in Taiwan have reported in the Journal of Natural Products on the isolation of erinacine S, which had increased the expression of an insulin-degrading enzyme in the cerebral cortex.

JNP paper

(−)-Jiadifenin synthesis

Glenn Micalizio and colleague at Dartmouth College have reported in JACS on the synthesis of jiadifenin.

 

JACS paper

Cipacinoids

Jian-Min Yue and co-workers from the Chinese Academy of Sciences have reported in Organic Letters on the isolation of cipacinoids A-D, which had protein tyrosine phosphatase 1B inhibition (17 micromolar).

 

OL paper

Enhancing water solubility of a drug (triptolide)

Gunda Georg and co-workers at the University of Minnesota reported in the Journal of Medicinal Chemistry on the addition of a phosphonooxymethyl group onto triptolide to increase its water solubility by greater than 3,580 times. (slight mistake: Scheme 2 in the paper has the use of benzoyl peroxide shown as “Bn2O2” when it should be “Bz2O2” – Bn2O2 would be benzyl peroxide). Another interesting point from this paper is that this natural product has multiple modes of action where it can covalently attach to proteins (XPB, xeroderma pigmentosum B) or non-covalently (DCTPP1, dCTP pyrophosphatase). Other modified attempts to form soluble prodrugs of this natural product (e.g. carboxylic acid, amino acid esters) resulted in difficult removal of the prodrug group.

J. Med. Chem. paper

Unciaphenol – Bergman cyclization product of uncialamycin

Raymond Anderson and co-workers at the University of British Columbia report in Organic Letters on unciaphenol, which has anti-HIV activity.

OL paper

Another validation for natural product research

The nobel prize in medicine announcement was made and the trio of winners (Satoshi Omura (avermectin), William Campbell (ivermectin), and Youyou Tu) had done natural product isolation work – one was Youyou Tu, the Chinese woman who discovered artemisinin (half of the prize)! An exciting win for natural product research!

Alpha-bisabolol

Victoriano Corpas-Lopez and co-workers at Universidad de Granada have reported in Journal of Natural Products on the use of alpha-bisabolol as a treatment for visceral leishmaniasis.

JNP paper