Scaffold natural product

The 2-azadiene system of the pyrazinone scaffold undergoes inter- and intramolecular cycloaddition reactions with a variety of (functionalized) alkenes forming bicyclic adducts, leading to the stereoselective generation of a variety of natural product analogues as well as peptidomimetics [58]. These bicyclic compounds could serve as key intermediates in the synthesis... 

The 2(lH)-pyrazinone system has received increased interest in the past two decades by both synthetic and biological research, due to its presence in a variety of natural and non-natural products as well as pharmacologically active compounds. The easy and diverse methods for the generation of this versatile scaffold make it a prime choice for the current pharmaceutical research hke thrombin inhibitors, substance P antagonists, etc. The rich 1,4-azadiene... 

Soldi AM. Libraries from natural product-like scaffolds. Curr Opin Chem Biol 2004 8 281-6. 

Lee, M.L. Schneider, G. (2001) Scaffold Architecture and Pharmacophoric Properties of Natural Products and Trade Drugs Application in the Design of Natural Product-Based Combinatorial Libraries. Journal of Combinatorial Chemistry, 3, 284-289. 

Didehydro-4-piperidinones of type 2-456 and 2-457 are useful intermediates for the synthesis of various substituted benzoquinolizines [243, 244, 245b-c] this scaffold is found in many natural products [245b-d]. 

A SN reaction-based domino route to clerodane diterpenoid tanabalin (2-488) [258] has been described by Watanabe s group (Scheme 2.111) [259]. This natural product is interesting as it exhibits potent insect antifeedant activity against the pink bollworm, Pectinophora gossypiella, a severe pest of the cotton plant The domino sequence towards the substituted trans-decalin 2-487 as the key scaffold is induced by an intermolecular alkylation of the (5-ke toes ter 2-484 with the iodoalkane 2-483 followed by an intramolecular Michael addition/aldol condensation (Robin-... 

The oxidative formation of p-benzoquinones from anilides such as 7-108 was used for the synthesis of the core scaffold of the natural products elisabethin A (7-106) and pseudopterosin A aglycone (7-107) (Scheme 7.30). Exposure of anilide 7-108 to DMP [53] led to the formation of the o-imidoquinone 7-109, which underwent an intramolecular Diels-Alder reaction to give 7-110 in 28% yield after hydration. In a competitive pathway, the p-quinone 7-111 is also formed from 7-108, which on heating in toluene again underwent an intramolecular Diels-Alder reaction to give cycloadduct 7-112 in 25% overall yield. Hydrolysis of 7-112 furnished the carbocyclic skeleton 7-113 of elisabethin A (7-106). 

Sequential pyrrolidine and hydantoin ring-forming reactions via intramolecular [2+3] cycloaddition have been applied to the stereoselective solid-phase synthesis of conformationally constrained tricyclic triazacyclopenta [C]pentalene scaffold 43 < 1999JOC8342>. These novel compounds 43 share the structural complexity characteristic of certain alkaloid natural products, angular triquinanes. The retrosynthetic analysis is shown in Scheme 87. 

Figure 2 Examples of natural product scaffolds missing from commercial sources.

More recently, Somfai and coworkers have reported on the efficient coupling of a set of carboxylic acids suitable as potential scaffolds for peptide synthesis to a polymer-bound hydrazide linker [24]. Indole-like scaffolds were selected for this small library synthesis as these structures are found in numerous natural products showing interesting activities. The best results were obtained using 2-(7-aza-l H-benzo-triazol-l-yl)-l,l,3,3-tetramethyluronium hexafluoride (HATU) and N,N-diisopropyl-ethylamine (DIEA) in N,N-dimethylformamide as a solvent. Heating the reaction mixtures at 180 °C for 10 min furnished the desired products in high yields (Scheme 7.4). In this application, no Fmoc protection of the indole nitrogen is required. 

Lycogalic acid (131) and halitulin (132) represent unique analogs (Fig. 8) to the 3,4-diaryl pyrrole scaffold of the natural products previously discussed. Lycogalic acid (131) contains indole rings attached at both C-3 and C-4 of... 

Natural products continue to play a dominant role in the discovery of leads for the development of drugs to treat human diseases. Such chemical agents have traditionally also played a major role in drug discovery and still constitute a prolific source of novel chemotypes or pharmacophores for medicinal chemistry. Natural product-based scaffolds find key importance in drug discovery as well as in optimizing chemical diversity... 

Bntler MS, Bnss AD. (2006) Natural products — the future scaffolds for novel antibiotics. Biochem Pharmacol 71 919-929. 

Lee ML, Schneider GJ. (2001) Scaffold architecture and pharmaco-phoric properties of natural products and trade drugs Application in the design of natural product-based combinatorial libraries. Comb Chem 3 284-289. 

Fig. 9 Solid phase DOS of partially "natural product-like" compounds by modification of a tricyclic scaffold...

The use of oxabicycloalkenes as scaffolds for natural product synthesis, including des3un-metrization approaches involving these molecules, has recently been reviewed see Hartung, I. V. Hoffmann, H. M. R. Angew. Chem. Int. Ed. 2004, 43, 1934-1949. 

These natural product scaffolds identified provided us with most of the antibiotic classes identified to date and they also provided the model for the many semisynthetic antibiotics approved in the recent years. Natural products contributed to more than 78% of the antibiotics approved between 1981 and 2002. Known targets in the clinic are inhibitors of bacterial... 

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