Natural product mimetics

Previous reviews on peptidomimetics have addressed pseudopeptides (11), macrocyclic mimetics (13), natural product mimetics (14), cyclic protease inhibitors (15), mimetics for receptor ligands (16-22), and earlier general overviews (23-29). This review will focus on the design process itself. Novel peptidomimetics in which the structural relationship between parent peptide and the peptidomimetic has been established by biophysical methods are used to clarify the principles. Successful approaches are highlighted to illustrate how these concepts are currently used. 

McKenzie, K. M., Videlock, E. I., Splittgerber, U., Austin, D. J. (2004). Simultaneous identification of multiple protein targets by using complementary-DNA phage display and a natural-product-mimetic probe. Angew. Chem. Int. Ed. Engl, 43, 4052-4055. 

Scheme 3.52), whereas the corresponding acetyl-protected donor gave little product under the same reaction conditions [512], Additionally, the trichloroacetimidate method has also been applied to synthesize other natural products, such as bupres-tin A and B [517], macrophylloside D [518] and neomycin mimetics [519]. 

The 3-indolylbenzoquinone fragment is a core structure in a number of biologically active natural products such as asterriquinones [49, 50]. The asterriquinones and demethylasterriquinones exhibit a wide spectrum of biological activities, including antitumor properties, and are inhibitors of HIV reverse transcriptase [51-53]. Asterriquinone Al has been shown to stop the cell cycle in G1 and promote apoptotic cell death [54, 55]. Recently, asterriquinone has been reported to be an orally active non-peptidyl mimetic of insulin with antidiabetic activity [56]. The simplest and the most straightforward approach for the synthesis of indol-... 

In addition, there are many important nonantibiotic uses of 2-azetidinones in fields ranging from enzyme inhibition [15-21] to gene activation [22], Systems containing one carbon atom common to two rings, spirocyclic compounds, represent an important structural organization. Spirocyclic p-lactams (Fig. 3) behave as p-tum mimetics [23-26] as well as enzyme inhibitors [27, 28], they are precursors of a,a-disubstituted p-amino acids [29-32], and the spiranic p-lactam moiety is present in chartellines and chartelamides [33-38], a family of marine natural products. Synthetic studies and biosynthetic speculation inspired by an unexpected reaction on the marine alkaloid chartelline C have been described [38],... 

The power of the Passerini and Ugi reactions in constructing polyfunctional molecules has been well appreciated since the early studies. The classical Passerini and Ugi reactions afford a-acyloxy carboxamides and a-acylamino amides respectively, that can be easily manipulated by post-condensation reactions, generating molecular diversity for drug discovery and natural product synthesis [22], This strategy has been widely applied to the synthesis of natural peptides and open-chain peptide mimetics covered in this section. 

The natural product asterriquinone Al (41) and asterriquinone derivatives containing the 3-indolylbenzoquinone structure exhibit a wide spectrum of biological activities, including antitumor properties, inhibition of HIV reverse transcriptase and as an orally active nonpeptidyl mimetic of insulin... 

The realization that a non-peptide natural product was mimickingthe action of a natural peptide effector led Farmer to postulate that other non-peptide structures might be found that would mimic other peptide effectors (7). His concept of peptide mimetic," which later was called "peptidomimetic," proposed that... 

Mimetics of naturally occurring structures often find use as pharmaceuticals. In other cases, they may help clarify issues of biological relevance that are not accessible using natural products. Often times, designed mimetic structures are isosteric with the structure they are designed to resemble, but contain a non-hydrolyzable linkage. 

There are numerous interglycosidic linkers other than amide linkers known in also natural products—Nature has already invented saccharide mimetics One example are the caUcheam-... 

A variety of macrocyclic natural products, either peptides or peptide-mimetic structures with HD AC inhibitory activity and promising pharmacological effects, have been reported. Some of them are shown in Fig. 5 for illustration for instance, romidepsin 9 (FK228) exhibits excellent class I inhibitory activity and has recently been approved by the FDA for the treatment of cutaneous T-cell lymphoma patients [58, 59]. Similarly, the marine natural product largazole 10 that demonstrates potent antiproliferative activity [60] and HC-toxin 11, a fungal metabolite with immunosuppressant activity, have been investigated as cytostatic agents [61, 62]. 

ABSTRACT More than 200 naturally occurring oligostilbenes isolated from plant kingdom are grouped into I-V structural types. They are a special kind of polyphenolic natural products with multi-faceted bioactivities. This article will review their classification, distribution, spectral characteristics, biological activities (anti-fungal, antibacterial, antioxidant, anti-inflammatory and anticarcinogenic activities, etc.) and mimetic biosynthesis. 

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