Formation of Nudicaulins In Vivo and In Vitro and the Biomimetic Synthesis and Bioactivity of O-Methylated Nudicaulin Derivatives

Abstract

Nudicaulins are yellow flower pigments accounting for the color of the petals of Papaver nudicaule (Papaveraceae). These glucosidic compounds belong to the small group of indole/flavonoid hybrid alkaloids. Here we describe in vivo and in vitro experiments which substantiate the strongly pH-dependent conversion of pelargonidin glucosides to nudicaulins as the final biosynthetic step of these alkaloids. Furthermore, we report the first synthesis of nudicaulin aglycon derivatives, starting with quercetin and ending up at the biomimetic fusion of a permethylated anthocyanidin with indole. A small library of nudicaulin derivatives with differently substituted indole units was prepared, and the antimicrobial, antiproliferative and cell toxicity data of the new compounds were determined. The synthetic procedure is considered suitable for preparing nudicaulin derivatives which are structurally modified in the indole and/or the polyphenolic part of the molecule and may have optimized pharmacological activities.

Coloration of Flowers by Flavonoids and Consequences of pH Dependent Absorption

“…As in the previous cases, the absorbance of M. cambrica flower extracts decreases steadily with increasing pH ( Figure 5C ). Similar as in P. nudicaule petal extracts, between pH = 4 and 7 a minor absorbance band at 510 nm arises ( Dudek et al, 2018 ). However, with increasing alkaline pH the absorbance band shifts again to lower wavelengths and rises in about the same wavelength range as that of the acid pigment state.…”

“…The Welsh poppy, M. cambrica , is a special case as its flowers are colored by nudicaulins, an unusual group of indole alkaloids, which are generated by combining anthocyanins with an indole ( Tatsis et al, 2013 ; Dudek et al, 2016 , 2018 ; Devlin and Sperry, 2020 ). We note that the pH-dependent processes of M. cambrica ‘s nudicaulin can be described by logistic functions with very similar pK-values as those of the anthocyanins ( Table 1 ).…”

“…We note that the pH-dependent processes of M. cambrica ‘s nudicaulin can be described by logistic functions with very similar pK-values as those of the anthocyanins ( Table 1 ). The nudicaulin pigments were analyzed in great detail in the Iceland poppy, P. nudicaule ( Tatsis et al, 2013 ; Dudek et al, 2016 , 2018 ). Interestingly, the yellow stamens of the yellow flowers contained carotenoids and not nudicaulins ( Dudek et al, 2016 ).…”

An Integrated—Omics/Chemistry Approach Unravels Enzymatic and Spontaneous Steps to Form Flavoalkaloidal Nudicaulin Pigments in Flowers of Papaver nudicaule L.

“…The structure consists of an indolic and a polyphenolic part, and free indole and pelargonidin glycosides were identified as the direct precursors by 13 C labelling experiments. The assembly of nudicaulin from these precursors was mimicked in vivo and in vitro [ 27 , 36 ]. The biosynthetic pathways of indole and pelargonidin are known from other plants—both compounds are derived from the shikimate and aromatic amino acid biosynthesis ( Figure 1 b).…”

“…Additionally, the final step—the fusion of indole and pelargonidin glycosides—is not fully understood. As the reaction was mimicked in vitro and in vivo and executed synthetically under acidic conditions [ 36 , 45 ], it could be a spontaneous non-enzymatic step. Unravelling of these questions is aggravated by the fact that P. nudicaule is not a model organism and no genomic information is available.…”