Study On Catalytic Selective Hydrogenation Of Avermectin

The avermectins,different from other insecticides,target the aminobutyric acid (GABA)-related chloride ion channels unique to nematodes,insects,ticks,and arachnids,with little or no mammalian toxicity.These compounds have a broad pharmacological spectrum against a wide variety of endo and ecto parasites including nematodes and anthropods.The avermectins are comprised of several structurally very similar compounds which consist of a 16-membered macrocyclic lactone ring. The avermectins can be subdivided into eight compound classes.Ivermectin,the first commercially available macrocyclic lactone endectocide,was discovered in a screening program at Merck in the mid-1970s.The selective reduction of avermectin to ivermectin is known and is carried out in a homogeneous phase with the Wilkinson catalyst.In order to prepare ivermectin from this starting material,a selective catalyst which only hydrogenates the 22,23 double bond is required.But the rhodium catalyst is very expensive and the catalyst can not be separated to reuse at the end of the reaction,to buy the catalyst spends most of the cost of ivermectin production. Although many efforts have been made to decrease the cost of the catalyst,no significant improvement was obtained.So the reaction of selective hydrogenation of avermectin with many other catalyst were systematically studied,in order to reduce the cost of prior homogeneous hydrogenation of avermectin with the aid of a rhodium-phosphine complex.The research contents includes the following main points:1 The selective hydrogenation of avermectin to ivermectin was studied by employing RhC1(PPh₃)₃ as catalyst,the effects of the various reaction conditions and the method of pretreatment for avermectin on the selective hydrogenation of avermectin were investigated,and the possible reaction mechanism was discussed.2 The Raney metal catalysts were firstly use in the catalytic selective hydrogenation reaction of avermectin.The separation and purification of the reaction products of the hydrogenation of avermectin by silica gel column chromatography were investigated. It was found that in the Raney Co,Ni and Cu catalysts,the hydrogenation was first occurred at the C3=C4 double bond of avermectin to give dihydroavermectin as one product,and then,the further hydrogenation occurred in C22=C23 to give tetrahydroavermectin as a byproduct.At the same time,Raney copper catalyst promoted with heteropolyacid(H₃PMo₁₂O₄₀)showed the higher catalytic selectivity than pure Raney copper catalyst.The high selectivity of this reaction was explained by the regular structure of the catalyst and the inhibited excess active sites of the Raney copper.3 The supported noble metal Rh,Ir,Ru and Pd catalysts were prepared and investigated.Different from the Raney metal catalysts,the hydrogenation was first occurred at the C22=C23 double bond of avermectin to give 22,23-dihydroavermectin (ivermectin)as the main product.The high selectivity of this reaction may be result from the especial environment of electron and cooperate effect in the supported noble metal catalysts.It was found thatγ-Al₂O₃ is the best support among Rh,Ir,Ru and Pd supported catalysts,and the catalysts of Ir/γ-Al₂O₃ and Rh/γ-Al₂O₃ showed the remarkable catalytic hydrogenation activity to ivermectin,this was explained by the higher dispersal of the metal and the strong support effect with the metal in the supported noble metal catalysts.