7 research outputs found
Rational Design 2-Hydroxypropylphosphonium Salts as Cancer Cell Mitochondria-Targeted Vectors: Synthesis, Structure, and Biological Properties
It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of (2-hydroxypropyl)triphenylphosphonium triflates 3 substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride etherate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides 4 were also obtained. The molecular and supramolecular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt 3 and L-α-phosphatidylcholine (PC) was employed for improving the bioavailability and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts 3 and 4 has promising potential of new vectors for targeted delivery into mitochondria of tumor cells
Stereoselective PCO/POC-Rearrangement of PâC-Cage Phosphorane in the Reaction of 4,5-Dimethyl-2-(2-oxo-1,2-diphenyl)ethoxy-1,3,2-dioxaphospholane with Hexafluoroacetone
Interaction
of 4,5-dimethyl-2-(2-oxo-1,2-diphenyl)Âethoxy-1,3,2-dioxaphospholane,
bearing a carboxyl group in the Îł-position with respect to the
phosphorus atom and obtained from <i>d</i>,<i>l</i>-butanediol, with hexafluoroacetone (CCl<sub>4</sub>, â40
°C) leads to the simultaneous formation of regio- and stereoisomeric
cage-like phosphoranes with phosphorusâcarbon and phosphorusâoxygen
bonds with a high stereoselectivity (>95%), whose structure was
determined by 1D and 2D NMR spectroscopy and XRD. When stored as a
solution in dichloromethane for one month, the PCO-isomer rearranges
into the thermodynamically more stable POC-isomer of the cage-like
phosphorane. Mild hydrolysis of the PCO/POC-isomers proceeds with
a high chemoselectivity and leads to the formation of PÂ(IV)-dioxaphospholane
derivatives. Acidic hydrolysis of the POC-isomer leads to the formation
of an oxirane derivative with an unexpectedly high stereoselectivity
(>95%). DFT calculations (using the PBE functional) allowed us
to obtain structures and energies of the initial phospholane, reaction
products (PCO/POC-isomers), and an intermediate PÂ(V)-oxaphosphirane