Anna Yu. Spivak

Synthesis and activity of new triphenylphosphonium derivatives of betulin and betulinic acid against Schistosoma mansoni in vitro and in vivo.

We studied the antischistosomal activity of betulin, betulinic acid and its 9 triphenylphosphonium derivatives characterized by a covalently linkage of the hydrophobic fragment of triterpenoid at C(2)- or C(30)-position with the triphenylphosphonium moiety via a hydrocarbon bridge. The triphenylphosphonium salts showed in vitro antischistosomal activity against newly transformed schistosomula (NTS) and adult worms of Schistosoma mansoni at low micromolar concentrations. In contrast betulin and betulinic acid were inactive against NTS and adult S. mansoni. Of the 9 triphenylphosphonium derivatives tested, the allyl salts 10 (IC50 of 0.76 μg/mL) and 11 (IC50 of 0.64 μg/mL) demonstrated the highest antischistosomal activity against adult S. mansoni. Low worm burden reductions of 22% were observed in vivo for these two compounds. In conclusion, triphenylphosphonium derivatives were obtained from available natural betulin by simple transformations, rendering it practical and useful for large scale application. However, further structural modifications are necessary to translate the promising antischistosomal in vitro activities into in vivo.

Triphenylphosphonium cations of betulinic acid derivatives: synthesis and antitumor activity

A series of lupane triterpenoid conjugates with the triphenylphosphonium cation, in which the terpenoid molecules are linked to one or two triphenylphosphonium moieties at the С-2, С-28, or С-30 positions by carbon–carbon or ester bonds, have been designed and synthesized as potential anti-cancer agents. The pharmacological results showed that all of the prepared triphenylphosphonium salts displayed considerable antitumor activities against the tested cancer murine tumor (Ehrlich ascites carcinoma, (Р-815), and human tumor (MCF-7) (IC50 < 2 μg/mL)) cell lines. The presence of the triphenylphosphonium cation in the triterpenoid conjugates markedly enhanced the cytotoxic action as compared to the parent compound (betulinic acid) (IC50 24.7 μg/mL for Ehrlich cells and 18.7 μg/mL for Р-815 cells), while the correlation between the cytotoxic activity and the chemical structure of phosphonium salts was not observed.

New possibilities in a synthesis of (2R,4'R,8'R)-α-tocopherol (natural vitamin E)

New methods for the synthesis of homochiral C14 and C15-terpenoids desired as building blocks for phytilic side chain of natural α-tocopherol have been developed. A natural phytone resulted from the proposed effective method of chlorophyll ozonolysis was used in a synthesis of optically active terpenoids. Chiral chroman compound for vitamin E, namely, (S)-(-)-6benzyloxy-3,4-dihydro-2,5,7,8-tetramethylchroman-2-methanol was obtained by enantioselective transesterification of the corresponding racemic alcohol catalysed by Amano PS lipase from Burkholderia cepacia in ionic liquid [bmim]PF6.