N-Linked derivatives

4- Aminoisoxazoles are obtained by reduction of 4-nitroisoxazoles with amalgamated aluminum, tin(II) chloride and hydrochloric acid, or zinc dust and acetic acid (62HC(17)1, p. 73). 

5- Acyl-4-aminoisoxazoles have been prepared by cyclization of a-(acylmethoxy-imino)nitriles in the presence of lithium hydroxide (equation 44) (80LA1623). 

5-Aminoisoxazoles have been synthesized by reaction of hydroxylamine with a-alkynic nitriles (317) (66CPBI277), with 3-ethoxyacrylonitriles (equation 10) (78KGS969) or with 

4- nitroisoxazole, has been synthesized by the reaction of nitromalondialdehyde with hydroxylamine and by nitration of isoxazole in mixed acid (63AHC(2)365). 3-Methyl-4-nitro- 

5- phenylisoxazole was obtained by reaction of 3-bromo-l-phenyl-l-butyne with sodium nitrite (80ZOR1328). 

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The oxidation of amidinothioureas by a range of oxidizing agents to give 3,5-diimino derivatives is still one of the most versatile methods for the synthesis of N-linked derivatives (see Section 5.08.9.4). An alternative method which gives symmetrical derivatives is the oxidation of A-arylthioureas to produce Hector s bases which readily isomerize to give 3,5-diamino-l,2,4-thiadiazoles (see Section 5.08.9.2). 

Many compounds containing the P-N link can be considered formally as derivatives of the oxoacids of phosphorus and their salts (pp. 510 -31) in which there has been isoclccironic replacement of ... 

Plant-based production systems are now being used commercially for the synthesis of foreign proteins [1-3]. Post-translational modification in plant cells is similar to that carried out by animal cells plant cells are also able to fold multimeric proteins correctly. The sites of glycosylation on plant-produced mammalian proteins are the same as on the native protein however, processing of N-linked glycans in the secretory pathway of plant cells results in a more diverse array of glycoforms than is produced in animal expression systems [4]. Glycoprotein activity is retained in plant-derived mammalian proteins. 

Fig. 15.4 Structure of glycans N-linked to IgG molecules expressed in hybridomas and transgenic plants. Glycans N-linked to plant-derived antibodies are structurally different from their mammalian counterparts. In contrast with antibodies produced in alfalfa, antibodies produced in tobacco plants present a very high glycan heterogeneity.

Glycosylation affects protein stability as well as immunogenicity. A prominent example is tobacco-derived erythropoeitin (EPO), which possesses smaller N-linked oligo-... 

We investigated the possibility that the N-linked 2-methylimidazole ring might not be the optimum one for 5-HT3 antagonist activity and considered the possibility that C-linked imidazole derivatives might have advantages. One of the first compounds prepared was the indolyl ketone (27), which was chosen on grounds of accessibility and synthesized by standard reactions from the protected aldehyde (26) (Scheme 7.4) [61]. 

In 1981, Potier et al. reported the isolation of N-oxyellipticine (240) from O. moorei (181). In the following year, Michel et al. reported the isolation of another N-oxyellipticine derivative, N-oxy-13-oxoellipticine (241), from the stem bark of S. dinklagei (184). Five years later, the same authors isolated from the bark of the same natural source, a novel, natural, bis-ellipticine alkaloid, strellidimine (242), in racemic form (221). Strellidimine represented the first example of a natural bis-ellipticine alkaloid, containing a 9-hydroxyellipticine (230) unit (see Scheme 2.56) linked to a 3,4-dihydroellipticine (236) unit (see Scheme 2.57) (221) (Scheme 2.59). 

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