ABSTRACT
The behavior of G3 factor and of its methylated or fluorinated analogues G3Me and G3F, was studied under Fe(II) conditions. Degradation products were isolated and characterized in each case. The use of labelled compounds allowed us to propose mechanisms in which a tertiary radical is involved. This radical rearranges by 5-exo-trig cyclization, or disproportionates in the case of G3Me. A correlation between antiplasmodial activity and stability of this radical is proposed.
Subject(s)
Ethers/chemistry , Ferrous Compounds/chemistry , Magnetic Resonance Spectroscopy/methods , Peroxides/chemistry , Oxidation-ReductionABSTRACT
Alkylation of the peroxyhemiketal function is described and all synthesised endoperoxides show good antimalarial activity. New rearrangement reactions in the presence of CsCO3, and preliminary results on Fe(II) chemical reduction of the O-O bond are presented.
Subject(s)
Antimalarials/chemical synthesis , Antimalarials/pharmacology , Peroxides/chemical synthesis , Peroxides/pharmacology , Alkylation , Animals , Antimalarials/chemistry , Peroxides/chemistry , Plasmodium falciparum/drug effectsABSTRACT
We developed a stereocontrolled route allowing potential access to the eight isomers of 4-benzylaminohex-5-ene-1,2,3-triol in two or four steps and ca. 50% yield from readily available chiral nonracemic cis- or trans-alpha,beta-epoxyimine precursors. A new (NH(4))(2)CO(3)-based carboxylation/intramolecular cyclization sequence allowed regio- and stereocontrolled C-3 epoxide opening while neat C-2 hydrolysis was ensured by simple aqueous acidic treatment.
Subject(s)
Hexanols/chemical synthesis , Cyclization , Epoxy Compounds/chemical synthesis , Epoxy Compounds/chemistry , Hydrolysis , Molecular Conformation , StereoisomerismABSTRACT
New endoperoxides, related to the natural phytohormones known as G factors (G1, G2, G3), were modified on the side chain and the ketalic position. An unexpected rearrangement, specific to one diastereoisomer was observed in the deprotection step of O-silylated compounds and attributed to a hexacoordinated fluorosilicon intermediate. The reduction potential of these new peroxides was determined. They exhibited good to moderate antimalarial activity, greatly related to the presence of peroxyketal function.
Subject(s)
Antimalarials/pharmacology , Plant Growth Regulators/pharmacology , Animals , Antimalarials/chemistry , Carboxylic Acids/chemistry , Electrochemistry , Plant Growth Regulators/chemistry , Plasmodium falciparum/drug effects , Plasmodium falciparum/growth & development , Prostaglandin Endoperoxides, Synthetic/chemical synthesis , Prostaglandin Endoperoxides, Synthetic/pharmacologyABSTRACT
(-)-Lentiginosine and its pyrrolizidinic analogue have been prepared in a straightforward five-step sequence from a versatile chiral cis-alpha,beta-epoxyamine.
Subject(s)
Alkaloids/chemical synthesis , Pyrrolizidine Alkaloids/chemistry , Alkaloids/pharmacology , Aspergillus niger/enzymology , Cyclization , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Glucan 1,4-alpha-Glucosidase/antagonists & inhibitors , Glucosides/metabolism , Oxidation-Reduction , Pyrrolizidine Alkaloids/pharmacology , StereoisomerismABSTRACT
The synthesis of the thymidine 2-deoxypolyoxin C analogue 10 from a noncarbohydrate precursor was achieved in 10 steps and 9% yield starting from a chiral gamma,delta-epoxy-beta-hydroxy ester 11 readily available from cis-2-butene-1,4-diol. The main steps concern the stereo- and regioselective opening of the epoxide ring by an azide anion, the stereoselective introduction of the thymine base, and the transformation of the primary alcohol to the acid functionality of the final product. Two other approaches have also been investigated.
