Halogenated biological activities

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

Amongst synthetic quinoxalines, numerous types of biological activity have been reported. 5,6,7,8-Tetrachloroquinoxaline (132) and related halogenated derivatives have found use in fungicidal formulations. Phosphoric esters of 6-hydroxyquinoxaline (133) have found use in insecticidal preparations, and phosphoric ester derivatives of 2-hydroxyquinoxalines, such as (134), function as anthelmintics. 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

The biological activity of several halogenated herbicides in water is destroyed by ultraviolet irradiation (18). Irradiation seems to be a promising method for decontaminating small quantities of pesticides. The chemical similarity between the chlorinated dioxins and other chlo-rinted aromatic compounds suggested that if there were parallels in their photochemical behavior, sunlight might destroy dioxins in the environment. 

Biological activity in this series shows considerable tolerance for modification in the ester moiety as well. Esters in which one of the aromatic rings is fully reduced still show good anticholinergic activity. One such agent, propenzolate (66), is prepared by displacement of halogen from N-methyl-3-chloropiperidine (64) by the sodium salt of acid... 

The recurring theme in work on corticoids discussed thus far with the exception of the 17-desoxy compounds consisted in the introduction of additional functions to the basic cortisone molecule. Some further success in producing biologically active molecules has been achieved by substituting unnatural functions for those present in the protoype molecule. Thus the hydroxyl groups at both C-ll and C-21 can be replaced by halogen with retention of activity. 

Our electrostatic potential analyses of TCDD, 22-25, and a number of other dibenzo-p-dioxins have allowed us to make some generalizations about the F(r) pattern that appears to lead to high biological activity for this class of halogenated aromatics. These are listed below ... 

Gauthier et al. <2005JOC5938> elaborated a synthetic route to 148, which is an important biologically active compound. These authors found that 147 can be subjected directly to cross-coupling process with the appropriate boronic acid, and there is no need for the halogenation of 147 to an intermediate for this cross-coupling. The product 148 was obtained in kilogram quantities in almost quantitative yield. 

S., Vatter, S., Chahbane, N., Lenoir, D., Schramm, K.W. and Scherer, G. (2005) Biological activity and physicochemical parameters of marine halogenated natural products 2,3,3, 4,4, 5,5 -heptachloro-l -methyl-1,2 -bipyrrole and 2,4,6-tribromoanisole. Archives of Environmental Contamination and Toxicology, 48, 1-9. 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

The toxicities of those perhalogenated iodoalkanes used in industrial telomerization processes, in laser-based nucleus fusion research and for other applications have been published in some detail (Table 16). The short chain linear perfluoroiodoalkanes are nontoxie. Branching of the carbon backbone and lower bond strength of the halogens involved are responsible for higher biological activity, observed in some cases. The higher linear perfluorinated iodoalkanes are completely inert materials. 

---