Synthesis of cytotoxically active derivatives based on alkylated 2,3-seco-triterpenoids

Synthesis, Cyclization, and Cytotoxic Activity of 2,3-Secolupane Triterpenoids With an Ethylketone Fragment

“…Pyridinium bromide perbromide (C 5 H 6 Br 3 N) was used as a brominating agent for the preparation of α-monobromoethyl ketone 6 on the basis of C(30) aldehyde 4. 10 A possibility was studied of intramolecular nitrile-anionic cyclization of 2,3-secotriterpenic derivatives 3 to 6 under conditions of basic catalysis. When 3-ethyl-3-ketone 3 or 20-methyl-3-ethyldiketone 5 was boiled in a t-BuOK-t-BuOH mixture, reactions proceeded via the oxo-nitrile mechanism with formation of the corresponding A-pentacyclic 3-ethyl α,β-alkenenitriles 8 and 7 with 44% to 45% yields.…”

“…Our group has reported 9 -12 that C(3) methyl substitution by Grignard reaction allows the modification of A-seco- and A-pentacyclic triterpenoids and the synthesis of novel biologically active derivatives. Thus, 2,3-seco-18αH-oleanane 3-methyl-3-ketone combining high virus-inhibitory activities against herpes simplex virus type 1 and HIV-1, 9 and 2,3-secolupane α-monobromomethyl ketone with a high antitumor activity 10,11 were synthesized. Recently, we also described the synthesis of C(3)-ethyl substituted 18-αH-oleanane derivatives with weak cytotoxicity.…”

Recent Achievements in Medicinal and Supramolecular Chemistry of Betulinic Acid and Its Derivatives ‡

“…Thus, a synthesis of novel 2,3-seco-triterpenoids and triterpenoids bearing five-membered ring A, all displaying cytotoxicity, was published (Scheme 1) [42]. The compounds were prepared on the basis of betulone ( 4 ) that is modified to the 2-oxime derivative of betulonic acid ( 5 ) by a several steps procedure [42,43].…”

“…Thus, a synthesis of novel 2,3-seco-triterpenoids and triterpenoids bearing five-membered ring A, all displaying cytotoxicity, was published (Scheme 1) [42]. The compounds were prepared on the basis of betulone ( 4 ) that is modified to the 2-oxime derivative of betulonic acid ( 5 ) by a several steps procedure [42,43]. Further structural modification of 5 (Scheme 1) resulted in a subsequent synthesis of the compounds 6 – 9 [42], representing the most cytotoxic structures of this series of compounds [42].…”

“…The compounds were prepared on the basis of betulone ( 4 ) that is modified to the 2-oxime derivative of betulonic acid ( 5 ) by a several steps procedure [42,43]. Further structural modification of 5 (Scheme 1) resulted in a subsequent synthesis of the compounds 6 – 9 [42], representing the most cytotoxic structures of this series of compounds [42]. Their antiproliferative activity was tested on various human cancer cell lines.…”