Biologically Active Derivatives

The discovery that vitamin was metabolized to biologically active derivatives led to a significant effort to prepare 25-hydroxy vitamin and, subsequendy, the 1 a-hydroxy and 1,25 dihydroxy derivatives. Initial attempts centered around modification of steroidal precursors, which were then converted to the D derivatives by conventional means. 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

VII. Biologically Active Deriv atives of the Isoxazole Series. . . 421... 

Alkylamines have a variety of applications in the chemical industry as starting materials for the preparation of insecticides and pharmaceuticals. Labetalol, for instance, a so-called /3-blocker used for the treatment of hi h blood pressure, is prepared by SN2 reaction of an epoxide with a primary amine. The substance marketed for drug use is a mixture of all four possible stereoisomers, but the biological activity derives primarily from the (R,R) isomer. 

The herbicide activity ascribed to the 1,2,4-oxadiazole derivative 67 (60) has prompted the search for other biologically active derivatives. This example was prepared from the corresponding 5-chloromethyl-1,2,4-oxadiazole 63 via conversion to the HHT 65 through the aminomethyl analog 64. Reaction of the HHT 65 with diethyl phosphite under neat conditions produced the desired diethyl ester intermediate 66, which was hydrolyzed to 67. 

Galardy, R.E. et al. (1978) Biologically active derivatives of angiotensin for labeling cellular receptors. J. Med. Chem. 21, 1279. 

The well-known reaction of hydrazides with cyanogen bromide, usually performed in the presence of potassium or sodium bicarbonate, affords 2-amino-5-substituted-l,3,4-oxadiazoles. In the past 10 years, this reaction has been applied several times, mainly in order to obtain biologically active derivatives. 

Arachidonic acid is converted to biologically active derivatives by cyclooxygenases and lipoxygenases. 

Prostaglandins (PG s) and leukotrienes (LT s) are biologically active derivatives of 20 carbon atom polyunsaturated essential fatty acids, which contains 3, 4 or 5 double bonds (e.g. 5,8,11,14-eicosatetraenoic acid i.e., arachidonic acid). 

Proton and carbon-13 NMR studies of the protonation of biologically active derivatives of pyrimido[4,5-6][l,4]thiazines were reported in 1979 [Pg.776]

Thiazoles as intermediates for carbohydrates and biologically active derivatives 89PS(43)25. 

Biologically active derivatives of 2-phenylethylamine—adrenaline, noradrenaline, methamphetamine, mescaline, dopamine, fentanyl (a synthetic narcotic), and sumatriptan (Imitrex, a synthetic pain reliever) (Section 25.6C)... 

There are three isomeric thienopyrimidines thieno[2,3-d]pyrimidines 1, thieno[3,2-d]pyrimidines 2, and thieno[3,4- fjpyrimidines 3. The present review deals with these three systems and their chemically and biologically active derivatives. However, it will not cover any additional condensed systems owing to the large number of references in this area. 

Royer, R. E., Deck, L. M., Campos, N. M., Hunsaker, L. A., and Vander Jagt, D. L. (1986). Biologically active derivatives of gossypol Synthesis and antimalarial activities of peri-acylated gossylic nitriles. ]. Med. Chem. 29,1799-1801. 

Fig. 18.3 Structures of coumarin and some biologically active derivatives...

---