Xylochemical Synthesis of Cytotoxic 2-Aminophenoxazinone-Type Natural Products Through Oxidative Cross Coupling

Abstract

Today, the total synthesis of natural products mostly relies on the use of petroleum-based starting materials. The commercial availability of building blocks of this type often deflects attention away from lengthy synthetic routes required for the reintroduction of heteroatom substitution patterns lost in the geological process of kerogenesis. Herein, the use of wood-based starting materials, the so-called xylochemicals, for the synthesis of 2-aminophenoxazinone natural products is presented. The inherent heteroatom substitution patterns as well as chemical functionalities were employed and permitted a short and straightforward synthetic strategy. Moreover, a novel and “green” method for constructing the 2-aminophenoxazinone moiety was developed. A series of natural products was prepared and their cytotoxic properties were examined.

M[TPP]Cl (M = Fe or Mn)-Catalyzed Oxidative Amination of Phenols by Primary and Secondary Anilines

“…To demonstrate the scalability of this reaction, benzoquinone anil 3 was prepared on a 3 mmol scale in 70% yield. The phenoxazinone is a common structural motif in natural products 26 and in pharmaceutically active compounds. 27 The homocoupling of 2-aminophenol ( 1e ) and the cross-coupling with 2-amino-(4- t -Bu)phenol ( 1f ) afforded 2-aminophenoxazinone 20 and 21 in 83 and 82% yields, respectively.…”

The 15th Frank Warren Organic Chemistry Conference

“…[7] Prof. Dr.T ill Opatz discussed green synthetic routes toward complex heterocycles developed in his lab in which sunlight was harnesseda sa ne co-friendly source of energy for photocatalysis, [8] as well as the use of renewable xylochemically derived feedstocks for total synthesis. [9] The latter themew as continued by Dr.K ennedy Ngwira (Figure 2), who detailed his group's recent success in the synthesis of UV absorbers from phenolic compounds extracted from waste shells from cashew nuts. [10] Synthetic Organic Chemistry Methodology and Application…”

“…In a similar vein, Prof. Rosalyn Klein discussed case studies emanating from her lab on the application of green chemistry principles in the medicinal chemistry context, while Prof. Moira Bode (University of the Witwatersrand), described her group's recent advances in biocatalysis for the kinetic resolution of enantiopure Morita–Baylis–Hillman Adducts . Prof. Dr. Till Opatz discussed green synthetic routes toward complex heterocycles developed in his lab in which sunlight was harnessed as an eco‐friendly source of energy for photocatalysis, as well as the use of renewable xylochemically derived feedstocks for total synthesis . The latter theme was continued by Dr. Kennedy Ngwira (Figure ), who detailed his group's recent success in the synthesis of UV absorbers from phenolic compounds extracted from waste shells from cashew nuts …”

Laccase‐Mimicking Syntheses of Phenoxazinones by Aerobic Oxidative Homo‐ and Hetero‐Dimerizations of Aminophenols

“…For this transformation, many oxidative catalysts were investigated, ranging from laccases, [13a,16] metal complexes, [17] and organocatalyst, [18] to heterogeneous nanomaterials [19] and electro‐oxidation, [15b] etc. It was noteworthy that, although there have been many investigations of the homo‐dimerization of 1 s, little hetero‐dimerization of different 1 s has been reported in the literature [20] …”