Enzymatic catalysis of the Diels–Alder reaction in the biosynthesis of natural products

Abstract

Recent studies on enzymes catalyzing the Diels- Alder reaction. often named "Diels-Alderases", clearlydemonstrated the involvement of this synthetically useful reaction in the biosynthesis of natural products.This review covers natural Diels-Alder type cycloadducts. synthetic efforts on the chemical feasibility ofthe biosynthctic Diels - Alder reaction and a brief history of studies on Diels-Alderases. In addition,reaction mechanisms of artificial and natural Diels--Alderases are discussed.

A reação de Diels-Alder no início do século vinte um

“…Em 2003, Stocking e Williams apresentaram uma revisão sobre a reação de DielsAlder na biossíntese das principais classes de produtos naturais 35 e, em 2004, Oikawa e Tokiwano publicaram uma revisão com 280 referências sobre o mesmo assunto. 36 Alguns exemplos são apresentados na Figura 3, incluindo lovastatina, macrofomato, solanapirona A, chaetoglobosina A, spinosina A e clorotricina. 37 Watanabe descreve as possibilidades de biotecnologia com os conhecimentos adquiridos na biossíntese de produtos naturais pela reação de Diels-Alder.…”

Untitled

“…These dimers are composed of kauranoid and labdanoid units, and could be considered as taxonomic markers of the genus Xylopia. Three diterpenoid dimers linked through a six-membered ring via a Diels-Alder condensation of two labdanoid units, namely ent-methylisoozate dimer (13), ent-13′-nor-13′-oxomethylisoozate dimer (14) and ent-13-epoximethylisoozate dimer (15), were isolated from the stem barks of X. aromatica [29]. They were the first labdanoid dimers identified from the family Annonaceae.…”

Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

“…In the biosynthetic assembly line, the protection of the labile intermediates in an enzyme catalytic site provides kinetic stabilization and regulation of multimodal reactivity, allowing cascade synthesis with control of chemo-, regio-, stereo-, and even enantioselectivity. In principle, each evolved enzyme possesses a tailored fit that contributes to the catalysis of a particular mode of a skeleton-constructing transformation; 16 hence, the participation of a series of similar but functionally distinct biomacromolecular catalysts is required for skeletal diversification. Meanwhile, chemical emulation of divergent biogenic processes without the assistance of biomolecular catalysts 17 pose challenges, including (I) stabilization of the labile intermediates during handling in laboratory, (II)…”