Solid-phase Synthesis

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Solid-phase Synthesis

Solid-phase synthesis

The solid-phase synthesis is a method that combines organic synthesis with applications, pioneered by C. C. Leznoff, a professor at York University in Canada. In this approach, reagents are bound to a solid support material and synthesized stepwise in a reaction vessel using the chemistry of selective protecting groups. It is a heterogeneous reaction in which the reactants, solvent and catalyst remain in solution (If the catalyst is a polymer, it's in the solid phase).

Polymeric Reagents

The reagents commonly used in the solid-phase synthesis of pheromones are polymeric reagents. Polymeric reagents possess reactive organic groups bonded to a macromolecular support. In the solid-phase synthesis of insect sex pheromones, the commonly used polymer reagents are divided into polymer protective agents and polymer-supported Wittig reagents. And these polymer reagents are all supported by 1% - 2% cross-linked styrene–divinylbenzene copolymers.

Polymer protective agents

Trityl chloride polymer Triphenylchlorosilane polymer

Solid-phase synthesis

Polymer-supported Wittig reagents

Polymer-supported triphenylphosphine

Types of Solid-phase Reactions

There are several reaction types for the solid-phase synthesis of pheromones chemicals, such as Grignard coupling reactions, alkyne coupling reactions and Wittig reactions.

  • Grignard coupling reactions

The Grignard coupling reaction refers to the preparation of organomagnesium reagents from halogenated compounds with functional groups such as alkenyl, alkynyl and protected hydroxyl groups, and then the Grignard reagents coupled with other halogenated hydrocarbons or α, β-unsaturated carbonyl compounds to form carbon-carbon bonds. This method can be used to increase the length of the carbon chain.

Many insect sex pheromones have a conjugated diene structure, which is an important factor in determining the biological activity of the pheromone. Grignard coupling reaction enables stereoselective synthesis of disubstituted alkenes, so it has been used to synthesize a variety of insect sex pheromones such as the sex pheromones of Shecia siningensis Hsu, Aegeria apiformis Cl, Cydia pomonella, Chilo suppressalis, Lobesia botrana, etc.

  • Alkyne coupling reactions

The alkyne coupling reaction is the earliest synthetic method used in the chemical synthesis of pheromones, which allows the direct introduction of carbon-carbon triple bonds followed by the selective reduction of alkyne bonds to obtain double bonds. This method can be used to synthesize sex pheromones with high stereoselectivity.

The solid-phase method of this reaction uses trityl chloride resin as a hydroxyl protecting agent, which can effectively protect one hydroxyl group in the diol, and the other hydroxyl group can participate in the reaction. Alkynes made by solid-phase synthesis can be dissociated from polymers and reduced to cis- or trans- products in solution. In solid-phase synthesis, borane is often used to reduce alkynes because boron-containing impurities can be removed without oxidation. This method is used for the synthesis of insect sex pheromones such as the sex pheromones of Trichoplusia ni, Spodoptera frugiperda, Ostrinia nubilalis, Cydia strobilellus, etc.

  • Wittig reactions with polymeric reagents

Wittig reaction in the solid phase uses polymeric Wittig reagents which are bound to polymeric supports, allowing the reaction to proceed on the solid phase. Polymer supports like chlorotriphenylsilane or triphenylmethyl chloride are often used as protective agents to participate in the reaction.

What's more, the Wittig reactions can be divided into conventional synthesis and "inverse" synthesis.

Conventional synthesis

Conventional synthesis refers to the oxidation of a hydroxyl group of the diol to aldehyde group, followed by reaction with Wittig reagents.

"Inverse" synthesis

The "inverse" synthesis takes diol as the starting material, protects a hydroxyl group with a polymer, and then conducts the Wittig reaction to finally synthesize the pheromone.

Both synthetic routes can be used to synthesize the insect sex pheromones like pheromones of Spodoptera frugiperda, Ostrinia furnacalis, Conogethes punctiferalis, etc.

Advantages

Advantages

Polymer resins are reusable and raw materials are cheaper.

Products can be isolated by simple washing and filtration.

The reaction yield is improved due to fewer synthesis steps.

The reaction exhibits higher stereoselectivity.

Why choose Alfa Chemistry?

Alfa Chemistry is a professional supplier of insect pheromone, and has been committed to the research of insect pheromone. We provide high quality insect pheromone chemicals and related services. If you do not find the product you need in the catalog, please contact us, we are happy to provide you with more detailed services.

Please kindly note that our products and services are for research use only.
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