Natural [4 + 2]-Cyclases

Abstract

[4 + 2]-Cycloadditions are increasingly being recognized in the biosynthetic pathways of many structurally complex natural products. A relatively small collection of enzymes from these pathways have been demonstrated to increase rates of cyclization and impose stereochemical constraints on the reactions. While mechanistic investigation of these enzymes is just beginning, recent studies have provided new insights with implications for understanding their biosynthetic roles, mechanisms of catalysis and evolutionary origin.

Biocatalytic Strategies towards [4+2] Cycloadditions

“…In contrast, the crude enzyme selectivity was 87:13. [4] The crude enzymew as also shown to perform kinetic resolution of the cyclised (AE)-solanapyrone B through enantioselective oxidationt o( À)aldehyde solanapyrone A ( 7). This stereoselectivity indicates recognition of the decalin by the oxidase and perhaps coupling of the oxidation and cyclisation steps.…”

“…We will consider [4+ +2] cyclases to be any enzyme catalysing ar eactioni nw hich reactants with four and two atomsa re connected to form ac ycle of six while undergoing ar eduction in bond multiplicity. [6,7] Compared to the excellent reviewso ft he past years coveringp ericyclases, [7][8][9][10][11][12][13][14] here we also highlight the newest discoveries in plants and focus particularly on the catalytic devices of the naturale nzymes,designer enzymesa nd small molecule catalysts.…”

Enzymatic Cascade Reactions in Biosynthesis

“…Thedebate has often centered on whether transformations were actually concerted or stepwise.W en ote 3,3-rearrangements of the Claisen and Cope types below.O ver the past decade, an umber of purified enzymes have also been assigned as 4+ +2c yclization catalysts,a lthough it remains to be proven that any one of the purported 4+ +2r eactions proceed by ac oncerted mechanism (either synchronous or partially asynchronous). [57] Certainly,the 4+ +2conversions dramatically alter framework connectivity in the enzymatic products. [58] Some of them, we would put in the cascade category.…”

Enzymkaskadenreaktionen in der Biosynthese

“…Nicolaou et al [3a] und Baran [6] [57] Sicherlich verändern die [4+ +2]-Umwandlungen deutlich die Gerüstverknüpfung in den Produkten der enzymatischen Umwandlungen. Nicolaou et al [3a] und Baran [6] [57] Sicherlich verändern die [4+ +2]-Umwandlungen deutlich die Gerüstverknüpfung in den Produkten der enzymatischen Umwandlungen.…”

“…Die Debatten drehten sich oft darum, ob Umwandlungen konzertiert oder schrittweise ablaufen. Wire rwähnen unten 3,3-Umlagerungen vom Claisen-und Cope-Typ.I nd en letzten zehn Jahren wurden außerdem etliche gereinigte Enzyme als Katalysatoren für[ 4 + +2]-Cycloadditionen ermittelt, wenngleich noch nachgewiesen werden muss,dass all diese mutmaßlichen [4+ +2]-Reaktionen nach einem konzertierten Mechanismus ablaufen, sei er synchron oder teilweise asynchron [57]. Sicherlich verändern die [4+ +2]-Umwandlungen deutlich die Gerüstverknüpfung in den Produkten der enzymatischen Umwandlungen [58].…”