Complex botanical natural products: Synthesis of cephalotaxus esters and of the C19-diterpenoid skeleton of aconitum and delphinium alkaloids

cephalotaxine;cephalotaxus esters;harringtonine;homoharringtonine;homodeoxyharringtonine;anhydroharringtonine;deoxyharringtonine;total synthesis;natural products;aconitum;delphinium;C19-diterpenoids;aconitine;alkaloid;radical;N-acyl iminium;iminium;radical conjugate addition;ion channel;deoxyhomoharringtonine

Wilmot, Jeremy T.

关键词: cephalotaxine;    cephalotaxus esters;    harringtonine;    homoharringtonine;    homodeoxyharringtonine;    anhydroharringtonine;    deoxyharringtonine;    total synthesis;    natural products;    aconitum;    delphinium;    C19-diterpenoids;    aconitine;    alkaloid;    radical;    N-acyl iminium;    iminium;    radical conjugate addition;    ion channel;    deoxyhomoharringtonine;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/18298/Wilmot_Jeremy.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The Cephalotaxus esters are a class of alkaloids extracted from plants of theCephalotaxus genus and have been shown to be potent inhibitors of P-388 murine leukemiacells. While direct acylation of cephalotaxine has been reported to be difficult, the constructionand acylation of cephalotaxine using a β-lactone acyl chain surrogate in the synthesis ofanhydroharringtonine, deoxyharringtonine, homodeoxyharringtonine, and homoharringtonine isdescribed. The natural esters as well as several non-natural analogues were tested againstvarious human cancer cell lines not previously challenged by these alkaloids. Variations in thestructure of the ester chain were found to confer differing activity profiles against vincristineresistant HL-60/RV+.The Aconitum and Delphinium alkaloids comprise a family of compounds isolated fromthe Aconitum and Delphinium genera. Several compounds within this class show potent Na+ ionchannel activity ranging from the ion channel activation of aconitine to the ion channel blockingof lappaconitine. The completed synthesis of the skeleton of the C19-diterpenoid alkaloids isdescribed. Key steps include a Diels–Alder cycloaddition of a cyclopropene with a2,5-dioxycyclopenta-1,3-diene, a second Diels–Alder cycloaddition with a 2,5-dihydroazepine2π component, an intramolecular N-acyliminium cyclization, and a radical conjugate addition.