Medicinal interest

The greatest medicinal interest in pyridopyrimidines has been in another type of antibacterial derivative, the analogues of nalidixic acid, piromidic (68) (71CPB1426) and pipemidic (69) acids (75JMC74). 

A central focus in modem organic synthesis has been the development of highly efficient catalytic processes for the syntheses of natural and unnatural compounds of medicinal interest or intermediates useful for functional materials. A particularly attractive approach is to apply transition metal catalysed cyclisation reactions for the transformation of simple starting materials into monocyclic, bicyclic and polycyclic scaffolds that can be further elaborated into specific targets. 

The compounds of medicinal interest in this group so far have all been nonsteroidal antiinflammatory agents or analgesics. The prototype is benzydamine (55).15 An interesting alternate synthesis of this substance starts by sequential reaction of... 

We have pleasure in presenting eight reviews in this volume, all of which cover important advances in the chemistry and biology of products of medicinal interest. 

The literature contains a number of examples of imines of medicinal interest, including prodrugs and drug metabolites. These compounds may undergo metabolic hydrolysis as described below ... 

Panax ginseng is a perennial plant, growing 30-80 cm high. It has a round stem and bears terminal whorls of 5-8 palmate leaves (Gruenwald et al. 1998). The flowers have greenish-yellow corollas and grow in 1-3 umbels of 15-30 flowers. The fruit are red, pea-sized, and round. The rhizome is fusiform and is the principal part for medicinal interest. 

Polypetides of medicinal interest were reviewed earlier in this series [453] and developments have continued apace. Angiotensinamide, pentagastrin, tetra-cosactrin and felypressin are now either widely used or growing in importance and serve to illustrate how rapidly this branch of medicinal chemistry is expanding. 

Some Pyrimidines of Biological and Medicinal Interest—Part II... 

Many natural aromatic compounds are produced from the cyclization of poly- -keto chains by enzymic aldol and Claisen reactions. Examples include simple structures like orsellinic acid and phloracetophenone, and more complex highly modified structures of medicinal interest, such as mycophenolic acid, used as an immunosuppressant drug, the antifungal agent griseofulvin, and antibiotics of the tetracycline group, e.g. tetracycline itself. 

In contrast to the efficient reactions illustrated above, the use of 1,2-disubstituted aikenes as the 2n -components in the [5-1-2] cycloaddition has resulted, thus far, in low cycloadduct yields and complex mixtures, putatively arising from an intermediate metal-lacycle through competitive yS-hydride elimination. This limits access to the carbocyclic cores of some large and medicinally interesting natural product families (for example, those in Scheme 13.3). Introduction of an allene substrate, however, circumvents this limitation by installing the needed carbon-carbon bond while simultaneously leaving a handle for further functionalization (Scheme 13.10). For example, reduction of the exo-... 

A vast array of piperidine containing cores, both natural and synthetic, are of biological and medicinal interest. These heterocyclic scaffolds have been the subjects of considerable synthetic efforts, especially for the construction of optically active compounds. In this context, Khan et al. reported a catalytic bromodi-methylsulfonium bromide (BDMS) three-component reaction of 1,3-dicarbonyls with aromatic aldehydes and aromatic amines for a facile access to highly functionalized piperidines (Scheme 24) [104]. This strategy is an interesting illustration of... 

Dibenzo[a,g]quinolizinium ion is the prototype of a series of compounds initially prepared as intermediates for the synthesis of berbine alkaloids but which, as a class, have recently attracted medicinal interest per se (Scheme 99, Table 11). 

Nitrenium ions have been applied to the synthesis of macrocycles and other medicinally interesting compounds. The most successful reactions have been in cases where the nitrenium ion is covalently tethered to its intended target. Further efforts aimed at modulating the selectivity of these intermediates would increase their synthetic utility. 

These biological activities, combined with the use of these products as starting materials to prepare a- and p-amino acids, alkaloids, heterocycles, taxoids, and other types of compounds of biological and medicinal interest [39—4-7], provide the motivation to explore new methodologies for the synthesis of substances based on the p-lactam core. 

Actually, treating the two related ring systems in one chapter makes sense since in many cases they appear side by side in the same article or in a series of follow-up articles by the same author. There has been considerable activity concerning these two ring systems and this is certainly due to the large medicinal interest in 1,4-oxazepines and 1,4-thiazepines and their benzo derivatives. In this chapter, we have compiled the data abstracted from selected recent publications (since 1995) focusing on aspects of synthesis and reactivity as also has been the case in the previous treatments. The most important medicinal applications are mentioned at the end of the text. 

Iseki, Nagai, and Kobayashi prepared cinchonine-derived 4f and 4g from the corresponding bromides by the method B (Scheme 9.5), and realized the asymmetric trifluoromethylation of aldehydes and ketones with trifluoromethyltrimethylsilane (Me3SiCF3) catalyzed by these ammonium fluorides (Schemes 9.9 and 9.10) [19]. Although the enantioselectivities are not sufficiently high, this reaction system should offer a new access to various chiral trifluoromethylated molecules of analytical and medicinal interests through appropriate modifications. 

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