Unusually cyclized triterpenes: occurrence, biosynthesis and chemical synthesis

Abstract

The biosynthetic origin of most of triterpenes lies in cascade cyclizations and rearrangements of the acyclic precursors squalene (S) and 2,3-oxidosqualene (OS), processes leading to tetra- and pentacyclic triterpene skeleta. Apart from these, a number of triterpenoid structures derived from cyclization processes, that are different from those leading to tetra- and pentacyclic triterpenes, are also found in Nature. We have defined these processes as unusual cyclizations, and grouped them in three blocks, namely, incomplete cyclizations of the corresponding S-derived precursors, cyclizations of S or OS towards polycyclic triterpenes and subsequent cleavage of the preformed ring systems, and two independent cyclizations of the S- or OS-derived precursor. Apart from the molecules obtained from intact organisms, we will also consider the compounds obtained from in vitro cyclizations promoted by enzyme systems. After establishing which compounds could unambiguously be grouped under the term 'unusually cyclized triterpenes', this review moves on to the advances achieved in this kind of structure during the last ten years. These advances are presented in three parts. The first one presents the structure and biological properties of the unusual triterpenes reported in the last decade. The second part considers the main biosynthetic pathways which justify the formation of these triterpenes from their corresponding acyclic precursors. Finally, we look at the achievements made in different synthetic strategies directed at some of these molecules. One hundred and twenty-three references are cited.

Triterpenoids Manipulate a Broad Range of Virus-Host Fusion via Wrapping the HR2 Domain Prevalent in Viral Envelopes

“…Triterpenes, a class of secondary plant metabolites characterized by hydrophobic pentacyclic scaffolds, are found in a wide variety of herbal medicines with the capability of preventing various pathogen infections 5 . Cell-based studies have confirmed that oleanolic acid (OA) and betulinic acid (BA), a lupane-type triterpene,…”

Globostelletins A–I, cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata

“…Isomalabaricatrienol as produced by Tyr510 mutants is considered a putative precursor of isomalabaricane triterpenoids in sponges. 20,21 Thus, the various lengths of the side chains of compounds 1-12 are assumed as the products to be generated by oxidative degradation from isomalabaricane triterpenoid 22 (Fig. 2).…”

Celastraceae Family: Source of Pentacyclic Triterpenes with Potential Biological Activity

“…41 Os terpenos constituem uma ampla classe de produtos naturais, que possuem muitas funções no reino vegetal e na saúde humana. 42 Esta classe de substâncias defendem muitas espécies de plantas, animais e micro-organismos contra predadores, patógenos e competidores, e estão envolvidas na transmissão de mensagens sobre a presença de alimento e organismos nocivos.…”

“…45 A origem desta diversidade está no mecanismo envolvido durante a sua biossíntese. 41 Por mais de meio século, cientistas estudam o mecanismo de formação dos triterpenos, "orquestrado" pelas triterpeno sintases, e considerada uma das mais complexas reações da natureza. A ampla ocorrência e diversidade estrutural deste grupo de terpenos suscitam uma questão: por que um organismo gastaria tanta energia na produção e acúmulo destes metabólitos?…”