Biogenesis and Biomimetic Chemistry: Can Complex Natural Products Be Assembled Spontaneously?

Abstract

With selected examples, we try to demonstrate that complex structures of natural products can be generated with surprising spontaneity. In such cases it appears that molecular complexity might emerge with minimal (if any) enzymatic assistance, through self‐construction mechanisms. Rearrangements of linear molecules, light‐induced reactions, dimerizations and multi‐component reactions could explain the formation of secondary metabolites through the intrinsic reactivity of their precursors. A few examples, amongst the most significant, are presented, along with efficient biomimetic syntheses that strengthen the hypotheses.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Monomeric Dihydroanthraquinones: A Chemoenzymatic Approach and its (Bio)synthetic Implications for Bisanthraquinones

“…As no other flavoskyrin‐type dimeric compound has been isolated from natural sources, it is conceivable that the dihydroanthraquinones undergo oxidative coupling by, for example, cytochrome P450 enzyme(s), without involving flavoskyrin. In addition, the role of spontaneity and aerial oxidation as a driving force for the formation of such complex molecules, which has been proposed in many biosynthetic pathways, cannot be ruled out . Hence, “modified bisanthraquinones” might also be biosynthesized using nonenzymatic spontaneous reactions of biosynthetic intermediates, a notion that needs further investigation.…”

“…In addition, the role of spontaneity and aerial oxidation as a driving force for the formation of such complex molecules, which has been proposed in many biosynthetic pathways, cannotb er uled out. [27] Hence, "modified bisanthraquinones" might also be biosynthesized using nonenzymatics pontaneous reactions of biosynthetic intermediates, an otion that needs further investigation.…”

Spontaneous Formation of Nitrarine and Polycyclic Skeletons Related to Nitraria Indolic Alkaloids under Non‐Enzymic Conditions

“…The results also clearly demonstrate the high propensity of cyclic six‐membered‐ring enamines to dimerize into kinetically and thermodynamically stablized tetrahydroanabasine‐type structures. Finally, this work also emphasizes the importance of spontaneous molecular self‐assembly in living organisms 19…”

Artifacts and Natural Substances Formed Spontaneously

“…Biomimetic synthesis literature offers delightful accounts of auto-assemblies under UV irradiation, the [2 + 2] photocycloaddition of α, β-unsaturated ketones or esters to alkenes or alkynes being largely used [6,55]. Natural products obtained using this strategy do not necessarily correspond to artifactual compounds, but rather illustrate peculiarities in the field of biosynthesis.…”

“…Nevertheless, many spontaneously self-assembled compounds may constitute borderline cases. Examples have been reviewed by Gravel and Poupon [6]. Artifacts of natural molecules are feared and abhorred by the common pharmacognosist.…”