Radomir Matovic

Alkylation of carbonyl compounds in the TiCl4-promoted reaction of trimethylsilyl enol ethers with ethylene oxide

Abstract Titanium tetrachloride promoted reaction of trimethylsilyl enol ethers with ethylene oxide affords homoaldol type products in moderate/good yields. The reaction is believed to proceed via the titanium enolates.

Titanium tetrachloride promoted reaction of silyl ketene acetals with epoxides : a new method for the synthesis of γ-butanolides

Abstract A new method for the synthesis of γ-butanolides is described. The titanium tetrachloride promoted reaction of silyl ketene acetals with epoxides, followed by acidic work-up, affords the corresponding butyrolactones in 44–83% yield.

Alkylation of carbonyl compounds in the TiCl4-promoted reaction of trimethylsilyl enol ethers with epoxides

Abstract Titanium tetrachloride promoted reaction of trimethylsilyl enol ethers with ethylene oxide affords homoaldol type products in moderate/good yields. Monosubstituted epoxides react regioselectively: the nucleophilic attack of the enolate occurs at the more substituted position of propene oxide whereas epichlorohydrin reacts at the less substituted end.

Synthesis of (−)‐Cytoxazone and (+)‐epi‐Cytoxazone: The Chiral Pool Approach

Abstract Immunomodulator (−)‐cytoxazone and its epimer (+)‐epi‐cytoxazone were synthesized starting from (D)‐(−)‐4‐hydroxyphenylglycine. Homologation of the amino acid was achieved via the corresponding aldehyde, by a cyanohydrin reaction. The racemization of highly sensible amido aldehyde was efficiently suppressed when the oxidation of the parent aminoalcohol was performed by a modified Dess‐Martin procedure.

A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids

The design, synthesis and biological evaluation of a novel C,D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.

Gold(I)-Catalyzed Domino Cyclizations of Diynes for the Synthesis of Functionalized Cyclohexenone Derivatives. Total Synthesis of (−)-Gabosine H and (−)-6-epi-Gabosine H

1,6-Diynes with a t-butylcarbonate group in the propargylic position undergo gold(I)-catalyzed domino-cyclization which affords α-hydroxycyclohexenones. The described sequence can be applied on functionalized, highly oxygenated substrates, as examplified in the synthesis of (-)-gabosine H and its epimer.

Substrate Stereocontrol in the Intramolecular Organocatalyzed Tsuji−Trost Reaction: Enantioselective Synthesis of Allokainates

Organocatalyzed Tsuji-Trost cyclization of 3b proceeds with asymmetric induction and allows for stereoselective synthesis of (+)-allokainic acid. The stereochemical outcome of the cyclization was predicted by calculations.

An efficient semisynthesis of 7-deoxypaclitaxel from taxine

A semisynthesis of 7-deoxypaclitaxel 4 is described, starting from taxine 6 – the most abundant naturally occurring taxane diterpene fraction. A key step in this transformation is a tandem reaction: stereoselective osmylation of cinnamic ester 14/intramolecularly assisted methanolysis of 16, which gives the key intermediate 5, along with the optically pure ester 17 – a precursor for the synthesis of the paclitaxel side-chain. In this way, the cinnamoyltaxicine 9 is converted into 7-deoxybaccatin III 25 in 11 steps, and in 15% overall yield.

Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen

Domino reactions of ketones with molecular oxygen in the presence of potassium hydroxide and potassium t-butoxide afford cyclic hydroperoxy acetals (3,5-dihydroxy-1,2-dioxanes). Mixed endoperoxides can also be obtained in a three-component reaction of two ketones and oxygen.