Natural Pharmaceutically Active Compounds

Modem HPLC finds its abundant applications not only confined to isolation of natural pharmaceutically active compounds, control of microbiological processes but also assay of pure drugs and their dosage forms. A few typical examples will be discussed below ... 

The occurrence of the indole subunit is well established within the class of natural products and pharmaceutically active compounds. Recently, the Reissig group developed an impressive procedure for the assembly of highly functionalized in-dolizidine derivatives, highlighting again the versatility of domino reactions [8]. The approach is based on a samarium(II) iodide-mediated radical cydization terminated by a subsequent alkylation which can be carried out in an intermolecular - as well as in an intramolecular - fashion. Reaction of ketone 3-11 with samarium(ll) iodide induced a 6-exo-trig cydization, furnishing a samarium enolate intermediate... 

Enzymes are useful catalysts for a broad diversity of chemical reactions that enable the synthesis of natural and unnatural highly pure pharmaceutically active compounds. However, proteins themselves can also be the pharmaceutical ingredients. 

The commercial availability of basic pyridine derivatives has encouraged a tremendous amount of research into pharmaceutically active compounds. Two reviews in particular list a large number of medicinal compounds (B-80MI20900,77CZ389) based on the pyridine ring. Likewise, the occurrence of benzopyridine natural products with chemotherapeutic activity has stimulated the production of synthetic materials from aromatic amine precursors. Some important examples are presented below. 

A variety of studies have been conducted in which the CD induced in pharmaceutically active compounds was used to characterize the nature of the inclusion complexes. The interaction of four barbiturates with B-cyclodextrin was studied by solubility and chiroptical methods [55]. It was found that the solubility of the barbiturates increased significantly upon formation of the inclusion complexes, and this enhancement was used to deduce the formation constants for the associated species. The induced CD data were also used to evaluate the strength of the complexes, with the relative strength of interaction with 6-cyclodextrin being phenobarbital > pentobarbital > amobarbital > barbital. 

In particular, the non-naturally occurring amino acid L-tert-leucine has received significant attention due to several pharmaceutically active compounds into which it is incorporated[1). HIV-protease inhibitors developed by Novartis and Abbott are based on L-tert-leudne 2, 3. Roche has developed the anti-arthritic compound Ro 31-9790 based on its potent inhibition of collagenase 41 and a key component in the synthesis of Ro 31-9790 is the methylamide of L-tert-leucine. Boehringer Ingelheim developed a series of compounds that inhibit the ribonucleotide redudase of Herpes... 

This chapter describes the total synthesis of natural products and pharmaceutically active compounds through transition-metal-mediated or -catalyzed... 

Xanthene and acridane derivatives are pharmaceutically active compounds, as well as natural compounds, and their synthesis has attracted much attention. Recently, Klussmann and co-workers reported the oxidative coupling of xanthene and other activated benzylic compounds with carbon-based nucleophiles such as ketones. The reaction proceeded smoothly under... 

Indole and isoquinolone nuclei are prominent structural units frequently found in numerous natural products and pharmaceutically active compounds. Thus, the search for new methodologies to obtain these scaffolds with different substitution patterns is a current major objective in organic synthesis. Similar to benzofuran synthesis, Aluraez et al. observed that the palladium-catalyzed cascade intramolecular alkyne aminopaUadation/intermolecular Heck-type coupling reaction under oxidative conditions is an efficient methodology for the synthesis of indole 217 and isoquinolone 219 derivatives, starting from readily available aniline 216 or benzamide 218 substrates and functional alkenes [77] (Scheme 6.60). 

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... 

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