105250-95-1

Upstream product

• 85031-59-0 dihydroartemisinic acid 
• 92590-56-2 [3R-(3α,3aβ,6β,6aβ,9b,9aα,9bβ)]-decahydro-3-hydroxy-3,8,9-trimethyl-naphtho-[1,8-bc]-pyran-2(3H)-one 
• 129145-24-0 (3aS,6R,6aS,9aS,9bS)-3,6,9-Trimethyl-2,3,3a,4,5,6,6a,7,9a,9b-decahydro-benzo[de]chromene 
• 129145-25-1 (3aS,6R,6aS,9R,9aS,9bS)-3,6,9-Trimethyl-dodecahydro-benzo[de]chromen-9-ol 
• 67-56-1 methanol 
• 129145-26-2 Sodium; (R)-2-((1R,4R,4aS,7R,8S,8aS)-7,8-dihydroxy-4,7-dimethyl-decahydro-naphthalen-1-yl)-propionate 

Downstream Products

• 103775-34-4 (R)-2-[(1R,2S,3S,4R)-2-Formyl-4-methyl-3-(3-oxo-butyl)-cyclohexyl]-propionic acid methyl ester 

Relevant academic research and scientific papers

Synthesis of [15,15,15-2H3]-Dihydroartemisinic Acid and Isotope Studies Support a Mixed Mechanism in the Endoperoxide Formation to Artemisinin

Artemisinin is the plant natural product used to treat malaria. The endoperoxide bridge of artemisinin confers its antiparasitic properties. Dihydroartemisinic acid is the biosynthetic precursor of artemisinin that was previously shown to nonenzymatically undergo endoperoxide formation to yield artemisinin. This report discloses the synthesis of [15,15,15-2H3]-dihydroartemisinic acid and its use to determine the mechanism of endoperoxide formation. Several new observations were made: (i) Ultraviolet-C (UV-C) radiation initially accelerates artemisinin formation and subsequently promotes homolytic cleavage of the O-O bond and rearrangement of artemisinin to a different product, and (ii) dideuterated and trideuterated dihydroartemisinic acid isotopologues at C3 and C15 converted to artemisinin at a slower rate compared to nondeuterated dihydroartemisinic acid, revealing a kinetic isotope effect in the initial ene reaction toward endoperoxide formation (kH/kD～ 2-3). (iii) The rate of conversion from dihydroartemisinic acid to artemisinin increased with the amount of dihydroartemisinic acid, suggesting an intermolecular interaction to promote endoperoxide formation, and (iv)18O2-labeling showed incorporation of three and four oxygen atoms from molecular oxygen into the endoperoxide bridge of artemisinin. These results reveal new insights toward understanding the mechanism of endoperoxide formation in artemisinin biosynthesis.

The mechanism of the spontaneous autoxidation of dihydroartemisinic acid

Dihydroartemisinic acid undergoes slow spontaneous autoxidation to artemisinin and other natural products, which have been reported from the medicinal plant Artemisia annua. The mechanism of this complex transformation is shown to involve four steps: (i) initial reaction of the Δ4.5-double bond of dihydroartemisinic acid with molecular oxygen, (ii) Hock cleavage of the resulting tertiary allylic hydroperoxide; (iii) oxygenation of the enol product from Hock cleavage; and (iv) cyclization of the resulting vicinal hydroperoxyl-aldehyde to the 1,2,4-trioxane system of artemisinin.

Stereoselective synthesis of artemisinin

A stereoselective synthesis of artemisinin 11 based on intramolecular Diels-Alder reaction of the triene 4 derived from (+)isolimonene 2 is described.