Cristina Pesenti

The Influence of Fluorinated Molecules (Semiochemicals and Enzyme Substrate Analogues) on the Insect Communication System

Can the introduction of fluorine atoms affect the bioactivity of natural semiochemicals? Can fluorine contribute in the creation of specific enzyme inhibitors to interrupt or disrupt the insect communication system? The first step for the bioactivity of a molecule is interaction with the biological sensor. Hydrogen and fluorine are almost bioisosteric and the receptor site of the enzyme can still recognize and accept the fluoro analogue of its natural substrate. However, the peculiar electronegativity of the fluorine atom can affect the binding, absorption, and transport of the molecule. The differences in the molecules electronic properties can lead to differences in the chemical interactions between the receptor and the fluorinated substrate. Fluorine introduction can modify the metabolic stability and pathway of the semiochemicals in many different ways. Fluorinated analogues can show synergism, inhibition, or hyperagonism effects on insect behaviors, that is, the activity of the nonfluorinated parent compounds can be mimicked, lost, or increased. In any case, the fluorinated molecules can interact with the bioreceptors in a new and disrupting way. The semiochemicals are olfactory substances: fluorine can affect their volatility or smell. Production of semiochemicals from exogenous substances, perception at antennal receptors, and processing of biological responses are the main steps of communication among insects. In the production step, the fluorinated molecules can interact with enzymes that catalyze the biosynthesis of the natural pheromones. In the perception step, fluorinated semiochemicals can interact with the olfactory receptor cells; this often leads to totally unpredictable behaviors. Fluorinated molecules have been developed as probes to elucidate the complex chemorecognition processes of insects. Many of these molecules have been tested to find highly effective behavior‐modifying chemicals. New analogues have been synthesized to investigate the metabolic pathway of a pheromone molecule and many of them are promising disrupting agents. Despite such titanic research efforts, the results have often been random, rational trends in the induced behaviors have sometimes been impossible to find, and practical applications of the fluorinated semiochemicals are still uncertain.

Stereoselective Synthesis of Fluorinated Isoxazolidines and 2,3‐Dihydroisoxazoles: A Cycloadditive Route to Enantiomerically Pure Amino Fluoro Alcohols

3-(Fluoroalkyl)isoxazolidines 6 and -2,3-dihydroisoxazoles 8 have been obtained in enantiomerically pure form with good diastereoselectivity by 1,3-dipolar cycloaddition of diethyl fumarate and dimethylacetylene dicarboxylate, respectively, to the chiral fluorinated nitrone (R)-5. The latter has been prepared from the β-fluoromethyl-β-oxo sulfoxide (RS)-1, by a synthetic sequence where the chiral and enantiomerically pure sulfinyl function acts as a removable source of chirality. Reductive opening of isoxazolidines 6 then afforded amino fluoromethyl diols 7 in good yields.

Synthesis of (−)-(1S,5R)- and (+)-(1R,5S)-trifluoroanalogues of frontalin

Abstract The synthesis of enantiomerically pure (−)-(1 S ,5 R )-1-trifluoromethyl frontalin 7 starting from (−)-(1 R )-menthyl ( S )-toluene-4-sulfinate, 5-pentenylmagnesium bromide and methyl trifluoroacetate is described. The synthetic procedures to obtain the enantiomer (+)-(1 R ,5 S )- 7 are also mentioned. Absolute stereochemistry was unambiguously assigned by X-ray analysis of intermediates 3 and 5 .

Stereoselective Synthesis of Both Enantiomers of Trifluoro-γ-valerolactone and Pentafluoro-γ-caprolactone

Both enantiomers of 5-(trifluoromethyl)dihydrofuran-2-one (1a) and 5-(pentafluoroethyl)dihydrofuran-2-one (1b) have been synthesised stereoselectively, in four steps, starting from chiral (R)- or (S)-3-[(4-methylphenyl)sulfinyl]propionic acid (2) and commercially available perfluorinated esters. Compound (+)-(S)-1b is the pentafluoro analogue of the aggregation pheromone of Trogoderma glabrum. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of 2-Fluoro Analogues of Frontalin

The synthesis of enantiomerically and diastereomerically pure (−)-(1R,2R,5R)- and (−)-(1R,2S,5R)-2-fluoro frontalin (7) starting from (+)-(1S)-menthyl-(R)-toluene-4-sulfinate, methylmagnesium bromide, methyl fluoroacetate, 4-pentenyl bromide and diazomethane is described. The absolute stereochemistry was unambiguously determined by X-ray analysis of (+)-(1S,2R,5S,RS)-5, an intermediate in the synthesis of the enantiomeric (+)-(1S,2R,5S)-2-fluoro frontalin (7).