Mario D. Bachi

Synthesis of α-alkylidene-γ-lactones by intramolecular addition of alkoxycarbonyl free-radicals to acetylenes

Abstract α-Alkylidene-γ-lactones are obtained by treatment of chloroformate and selenocarbonate derivatives of homopropargylic alcohols with tri-n-butylstannane.

An efficient synthesis of bridged-bicyclic peroxides structurally related to antimalarial yingzhaosu A based on radical co-oxygenation of thiols and monoterpenes

Abstract Synthesis of β-sulfenyl endoperoxides 9 was achieved by a four component sequential free radical reaction based on the application of the thiol-olefin-co-oxygenation reaction to monoterpenes, followed by in situ treatment with triphenylphosphine. β-Sulfenyl endoperoxides 9 were oxidized with m-CPBA to β-sulfonyl endoperoxides 10 . This process provides an efficient method for the preparation of peroxides containing the 2,3-dioxabicyclo[3.3.1]nonane system ( 2 ) characteristic of antimalarial agents of the yingzhaosu A ( 3 ) family. A simple NMR diagnostic tool for the identification of stereoisomers is described.

Synthesis and in vitro antimalarial activity of sulfone endoperoxides

A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).

Free-radical annelation in the synthesis of bicyclic β-lactams. 5. Synthesis of carbapenams

Abstract Homolytic cyclization of some alkenyl β-lactams afforded carbapenams, by exo addition, when a vicinally disubstituted double double bond was involved, and carbacephams, by endo addition, when a terminal double bond was involved.

Free-radical annelation in the synthesis of bicyclic β-lactams. 1. Synthesis of 8-oxo-5-oxa-1-azabicyclo[4.2.0]octane and 9-oxo-6-oxa-1-azabicyclo[5.2.0]nonane derivatives

Abstract A new method for the synthesis of some fused bicyclic β-lactams based on the completion of the molecular backbone by a free-radical CC bond forming reaction is described.

Free-radical annelation in the synthesis of bicyclic β-lactams. synthesis of 1-oxacephem and 1-oxahomocephem derivatives.

The synthesis of tert-butyl 3-benzyl-1-oxa-Δ3-cephem-4-carboxylate (16) and other bicyclic β-lactams is described.

Free-radical annelation in the synthesis of bicyclic β-lactams. 2. Alternative use of chloro-, phenylseleno-, and phenylthio-functionalities as free-radical precursors

Abstract The tributyltin hydride-azobisisobutyronitrile induced cyclization of N-choloromethyl-, N-phenylselenomethyl-, and N-phenylthiomethyl-4-allyloxy-2-azetidinones to 9-oxo-6-oxa-1-azabicyclo[5.2.0]nonane is described.

Enantioselective total synthesis of (−)-α-kainic acid

a-Kainic acid and (-)-a-kainic acid ( 1) were synthesized. (-)-a-Kainic acid was obtained in 12% overall yield starting from tert-butyl isocyanoacetate. In the first step a chiral non-racemic oxazoline 19 was prepared. Oxazoline 19 was converted in three steps into the thioformimide 22 derived from a highly functionalized a-amino carboxylic acid. It was subjected to n-Bu3SnHlAIBN mediated free radical cyclization to enantiomerically pure pyrrolidine 25 which contain all the structural elements of (-)-a- kainic acid, except for the C-2 acetic acid moiety. This appendage was introduced by a new method of temporary sulfur connection. Accordingly, the 4-isopropenyl group was used as an anchor to which CH2C02Me was temporarily linked (26+13+ 14+15). It was then intramolecularly connected through a carbon-carbon bond to the pyrrolidine ring (15+ la), and eventually disconnected from its anchor by a sequential reductive double

Free-radical annelation in the synthesis of bcyclic β-lactams. 6. Synthesis of tert-butyl 2-benzylidene-1-carbapenam-3-carboxylate

Abstract tert-Butyl 2-benzylidene-1-carbapenam-3-carboxylate was obtained through the homolytic cyclization of a suitably substituted nonfused β-lactam

Synthesis of Thiabicyclic Heterocycles Through Free Radical Cyclization of β-Thioacrylates

Abstract 8-Aza-3-thiabicyclo[4.3.0]nonanes 7 and 8, 3-thiabicyclo[4.4.0]decanes 18, and 8-thiabicyclo[4.3.0]nonanes 31 were obtained from monocyclic precursors through free radical cyclizations involving a β-thioacrylate system as radical acceptor and a thionocarbonate as radical precursor. Oxidative sulfur extrusion in 3-thiabicyclo[4.4.0]decanes 18 afforded methyl (2-isopropenyl-5-methylcyclohexyl)-2-propenoates 35.