Study Toward the Total Synthesis of Pyrenophorin Estudos visando a síntese total da pirenoforina

Macrodiolides are macrocyclic compounds containing two ester groups in a cyclic chain. Of this class of compounds, Pyrenophorin (1) shows antifungal activity, and is produced from the pathogenic fungus Pyrenophora avenae. As this substance, derived from nature, is isolated in small quantities, an asymmetric synthesis using a simple and efficient methodology would be of great interest. The proposed synthetic route starts with the protection of propargyl alcohol 3 using DHP and feldspar as catalyst. Compound 5 obtained in this reaction was then subjected to acid-base reaction between the acetylenic proton and 1 eq. n-BuLi, leading to formation of the acetylide 5A. The 1,2- addition reaction between 5A and g-valerolactone (6) leads to the formation of alkinone 7 in 67% yield. Subsequently, compound 7 was subjected to a ketalization reaction using the same feldspar catalyst. Ketal 8 was formed under concomitant removal of the THP group. The product of this reaction (8) was then submitted to a reduction reaction of the triple bond to form olefin 9 with E configuration. Currently, the conditions for obtaining 10 by oxidation using Jones reagent, are being optimized. Compound 10, obtained as described, is being subjected to a macrolactonization reaction. Various conditions including the use of enzymes are being studied. In addition, a study involving the enantioselective synthesis of (R,R)-(-)-pyrenophorin, using enzymatic kinetic resolution of the racemic mixture of compound 8, is in progress in the group : Macrodiolídeos s o compostos macrocíclicos que apresentam em sua estrutura dois grupos ésteres contidos em uma cadeia cíclica. Dentre essa classe de compostos, a Pirenoforina (1) apresenta atividade antifúngica, e é produzida a partir do fungo patogênico Pyrenophora avenae. Como essa substancia, oriunda da natureza, é isolada em pequenas quantidades, uma forma de síntese assimétrica empregando uma metodologia simples e eficiente seria de grande interesse. A rota sintética proposta inicia-se com a prote o do álcool propargílico 3, empregando-se DHP e um catalisador neutro constituído por feldspato. O composto 5 obtido desta rea o, foi ent o submetido à rea o ácido base entre o próton acetilênico de 5 e 1 eq. de n-BuLi, levando a forma o do acetileto 5A. A rea o de adi o 1,2- entre 5A e a g-valerolactona (6), leva a forma o da alquinona 7 em 67 % de rendimento. Posteriormente, o composto 7 foi submetido à rea o de cetaliza o empregando o mesmo catalisador de feldspato, onde se observa a forma o do cetal 8, e remo o do grupo THP do álcool de form