Biological activity electrophilic substitution

The iacreased chemical stabiUty of the 6-deoxytetracyclines allows chemical modification with retention of biological activity electrophilic substitutions have been carried out at C-7 and C-9 under strongly acidic conditions (46—53). Reactions of 6-deoxy-6-demethyltetracycline [808-26-4] (16), C21H22N2O7, with electrophiles, such as nitrate ion (49), bromomium ion (46,47) (from N-bromosuccinimide), or N-hydroxymethylphthalimide (53), yielded 7-substituted tetracyclines. In the case of the nitration reaction, both the 7- and 9-nitro isomers (17, X = NO2, Y = H) and (17, X = H, Y = NO2) were obtained. 

Lithium magnesiate LiMgBus has been used for the smooth magnesium/bromine exchange of 5-bromo-2-methoxypyridine as an entry to the biologically active 5-substituted-2-methoxypyridines at 0 °C in THF, obtaining the desired electrophilically quenched products in reasonable yield [67]. This protocol displayed... 

Acetanilides, benzoyl-colour couplers in colour photography, 1, 372 Acetanilides, pivaloyl-colour couplers in colour photography, 1, 372 Acetazolamide — see l,3,4-Thiadiazole-2-sulfonamide, 5-acetamido-Acetic acid, acetamidocyano-ethyl ester, 1, 307 Acetic acid, 2-acylphenyl-isochroman-3-one synthesis from, 3, 858 Acetic acid, 3-benzo[6]thiophenyl-biological activity, 4, 912 Acetic acid, l,2-benzoxazol-3-yl-electrophilic substitution, 6, 48... 

Imidazo[ 1,2-e]thiazoles biological activity, 6, 1024 reactions, 6, 1041 synthesis, 6, 1048 Imidazo[2, l-6]thiazoles electrophilic substitution, 6, 979 synthesis, 6, 992, 993, 1010, 1018 Imidazo[3,l-6]thiazoles synthesis, 6, 986 Imidazo[5,l-6]thi azoles biological activity, 6, 1024 synthesis, 6, 1017 Imidazo[2,l-6]thiazolium chloride synthesis, 6, 1013... 

Both chemically and physiologically ORD and IRD are distinct processes. Because of the vicinal hydroxyl group, the I substituents in the outer ring are readily removed by electrophilic substitution reactions in contrast to the stable bonds of the I atoms with the inner ring. As to the biological implications, ORD is regarded as an activation step that converts the T4 to bioactive T3, whereas IRD is a catabolic reaction that not only inactivates T3 but also prevents its formation from T4. 

The same activation that allowed simple electrophilic substitution—oxidation to the N-oxide— can also allow a useful nucleophilic substitution. The positive nitrogen atom encourages nucleophilic attack and the oxygen atom can be turned into a leaving group with PCI3. Our example is nicotinic acid whose biological importance we will discuss in Chapter 50. 

The use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

A fine example demonstrating the use of an arylboron inteimediate was reported by Santaniello et al As part of a project aimed at evaluating the biological activity of 2-and 4-substituted estrogens a convenient synthesis of 2-hydroxyestradiol was needed. Classical electrophilic oxidations usually lead to equimolar amounts of 2- and 4-isomers which are not easy to separate, and thus a method for regioselective hydroxylation was required. 3-Methoxyestra-l,3,S(10)-trien-17 -yl acetate (12) reacted with mercuiy(II) acetate in dry acetonitrile, and the reaction mixture was then treated wiA saturated aqueous sodium chloride to give the 2-chloromercurio derivative (13) in 80% yield. This inteimediate was then exposed... 

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