Search

Pericyclic reactions are powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. Their role in biosynthesis is increasingly apparent, and mechanisms by which pericyclases can catalyse reactions are of major interest.sup.1. [4+2] cycloadditions (Diels-Alder reactions) have been widely used in organic synthesis.sup.2 for the formation of six-membered rings and are now well-established in biosynthesis.sup.3-6. [6+4] and other 'higher-order' cycloadditions were predicted.sup.7 in 1965, and are now increasingly common in the laboratory despite challenges arising from the generation of a highly strained ten-membered ring system.sup.8,9. However, although enzyme-catalysed [6+4] cycloadditions have been proposed.sup.10-12, they have not been proven to occur. Here we demonstrate a group of enzymes that catalyse a pericyclic [6+4] cycloaddition, which is a crucial step in the biosynthesis of streptoseomycin-type natural products. This type of pericyclase catalyses [6+4] and [4+2] cycloadditions through a single ambimodal transition state, which is consistent with previous proposals.sup.11,12. The [6+4] product is transformed to a less stable [4+2] adduct via a facile Cope rearrangement, and the [4+2] adduct is converted into the natural product enzymatically. Crystal structures of three pericyclases, computational simulations of potential energies and molecular dynamics, and site-directed mutagenesis establish the mechanism of this transformation. This work shows how enzymes are able to catalyse concerted pericyclic reactions involving ambimodal transition states. Enzymatic catalysis of pericyclic [6+4] cycloaddition reactions to form ten-membered rings is observed during biosynthesis of the macrocyclic antibiotic streptoseomycin, and the mechanism of these transformations is established., Author(s): Bo Zhang [sup.1] , Kai Biao Wang [sup.1] , Wen Wang [sup.1] , Xin Wang [sup.2] , Fang Liu [sup.2] , Jiapeng Zhu [sup.3] , Jing Shi [sup.1] , [...]

A series of six-membered rings bearing cis oriented vicinal carboxylate and sulfinate esters were treated with Grignard reagents with the intention of transforming them to p-carboalkoxy substituted sulfoxides. The expected outcome did not transpire and instead the substrates demonstrated the capacity to accept 3 equiv. of organometallic agent in an uncontrollable manner. As such, the substrates possessing eclipsing carboxylate and sulfinate esters accepted two organic ligands at the carboxylate functionality and one at the sulfinyl group. When isomer mixtures of sterically encumbered sulfinate esters were reacted, a single sulfoxide stereochemistry resulted. A mechanism involving the intermediacy of a sulfurane is proposed to account for the experimental observations. Key words: Grignard reagent, sulfinate ester, sulfoxide, addition reaction, sulfurane. Une serie de cycles a six membres portant des esters carboxyliques et sulfiniques vicinaux ont ete traites avec des reactifs de Grignard dans le but de les transformer en p-carboalkoxy sulfoxydes substitues. Le resultat espere n'a pas ete obtenu et, au lieu de cela, les substrats ont montre une capacite a accepter trois equivalents d'agent organometallique de maniere incontrolable. En tant que tels, les substrats portant des esters carboxyliques et sulfiniques en position eclipsante ont accepte deux ligands organiques au niveau de la fonction carboxylate et un au niveau du groupe sulfinyl. La reaction de melanges isomeriques d'esters sulfiniques steriquement encombres a debouche sur une seule stereochimie du sulfoxyde. Un mecanisme impliquant l'intermediaire d'un sulfurane est propose, qui permet d'expliquer les observations experimentales. [Traduit par la Redaction] Mots-cles : reactif de Grignard, ester sulfinique, sulfoxyde, reaction d'addition, sulfurane., Introduction For some time, sulfur containing functionality have been recognized as substituents that activate alkenes for the Diels-Alder cycloaddition. (1-10) The sulfone and sulfoxide containing adducts so formed can be [...]