Synthetic drugs and natural products

Chang TKH, Waxman DJ (2006) Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Drug Metab Rev 38 51-73... 

Tan s analysis of the first two components accounted for 84.2% of the original information, indicating that synthetic drugs and natural products show limited overlap of chemical space. 

Among these, polyazaheterocycles are particularly appreciated, as they often recur in pharmacologically active synthetic drugs and natural products ... 

Table 3.2 Average number of chiral centers in synthetics, drugs and natural products. (Natural products are divided into subclasses related to their biological origin.)...

Subsequently, solid-phase strategies were developed for the synthesis of oligonucleotides, as well as for nonbiopolymer small molecules, such as synthetic drugs and natural products. In a solid-phase synthesis, the starting material (e.g., first residue or molecular scaffold) is attached to an insoluble solid support, such as a polymer or glass bead, via a chemical linker that can be cleaved under specific, orthogonal reaction conditions... 

Fig. 9.1 -5 Structures of synthetic drugs and natural products, (a) Representative examples of approved synthetic drugs, which are often rich in aromatic rings and nitrogen atoms, (b) Representative examples of clinically used natural products,... 

Fig. 9.1-7 Example of principle component analysis comparison of synthetic drugs and natural products. A set of 20 synthetic drugs, including the top 10 best-sellers in 2004, and 20 natural products was analyzed for nine molecular descriptors molecular weight, hydrophobicity (X log P or C log P), hydrogen-bond donors, hydrogen-bond acceptors, rotatable bonds, topological polar surface area [43], stereogenic centers, nitrogen atoms, oxygen atoms. PCA was used to reduce the nine-dimensional vectors to two-dimensional vectors, which were then replotted as shown. The first principal component accounts for 55.1% of the original information and the first two...

Historically, anticancer drugs have been discovered through large-scale screening of synthetic chemicals and natural products against animal tumor systems. The drugs discovered in the first two decades of cancer chemotherapy (1950-1970) primarily... 

We have shown organocatalysis to be a powerful tool for the synthesis of drugs and natural products. Our work and that of others have clearly demonstrated that organocatalytic strategies can cut down the total number of synthetic operations. As organocatalysts are usually non-toxic, air- and moisture-stable and often available from renewable sources, they are destined to have an impact on the development of future sustainable chemical processes. 

Abstract Heterocyclic structures are an integral part of numerous drugs and natural products and there is a considerable interest in efficient methods for their S3mthesis. A variety of multicomponent reactions (MCRs) provide access to heterocychc structures such as isocyanide based MCRs, dicarbonyl derivative and cycloaddition MCRs. MCR-derived heterocycles are typically prepared in few, versatile and atom efficient synthetic steps and exhibit anticancer, antioxidant and antimicrobial properties. 

An exhaustive analysis of 2995 molecule pairs extracted from the 98.1 version of Bioster database indicated that similarity measures based on 2D molecular fingerprints or electrostatic field descriptors were complementary although 2D methods could be adequate for similarity analyses [55]. To evaluate a range of similarity measures among synthetic substances and natural products, the Willett group also used 5024 compounds from Bioster database as well as sets of selected bioactive compounds from the more populous Chemical Abstract Service, ID-Alert, MACCS Drug Data Report, and NCI AIDS databases [56]. 

Metathesis reactions are very powerful tools to create C—C bonds and provide synthetic chemists with synthetic design based on an unprecedented retrosynthetic analysis of complex compounds in very elegant and efficient ways. As the impact of metathesis in modern synthetic chemistry of drug and natural product is evidenced by a number of publications and reviews, in this chapter, we describe the most illustrative strategies of metathesis and their applications to drug and natural product syntheses in line with types of olefin, enyne, and alkyne metathesis reactions. 

The application areas for LC-MS, as will be illustrated later, are diverse, encompassing both qualitative and quantitative determinations of both high-and low-molecular-weight materials, including synthetic polymers, biopolymers, environmental pollutants, pharmaceutical compounds (drugs and their metabolites) and natural products. In essence, it is used for any compounds which are found in complex matrices for which HPLC is the separation method of choice and where the mass spectrometer provides the necessary selectivity and sensitivity to provide quantitative information and/or it provides structural information that cannot be obtained by using other detectors. 

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