Spermidine acylations

Ac2NOMe selectively acylates a primary amine of a spermidine. ... 

The two primary amino groups of spermidine can be selectively acylated by the following two routes [151a]... 

Subsequently, the phthalylglutamic acid (Fig. 7.75), a dicarboxylic acid, was shown to be teratogenic in mice when given on days 7 to 9 of pregnancy. However, other work has indicated that the phthalimide ring is of importance in the teratogenicity. Other studies have indicated that thalidomide acylates aliphatic amines such as putrescine and spermidine, histones, RNA, and DNA and that it may also affect ribosomal integrity. 

An acyl chloride was used in the synthesis of the spermidine alkaloid cannabisativine (162) by Natsume and coworkers [92]. As shown in Scheme 53, the precursor 160 was hydrolyzed with Ba(OH)2 and the resulting amino acid was directly converted to acyl chloride HCl salt, a cold solution of which was added dropwise to a potassium carbonate suspension in acetonitrile to achieve the lactam closure. Deprotection of the methoxymethyl groups with acid afforded macrolactam 161 in 43% yield from 160. 

Very few reactions of this type have been reported. The glutaric acid derivative (70) was esterified with A-hydroxysuccinimide and the resulting product (98) was used to selectively acylate the secondary nitrogen of various spermidine derivatives (Scheme 9) <82S689>. 

Amides of the polyamine spermidine bearing aliphatic or hydroxycinnamic acyl residues are widely distributed in the plant kingdom (Bienz et al. 2002). In most cases the acyl moieties represent the latter residnes. For snch conjugates see Sect 6.6.4.3. A novel metabolite with an aUphatic acyl residue, A/ A/ -ditigloylspermi-dine, has been isolated from the seeds of Ipomoea nil (L.) Choisy collected on Zanzibar/Tanzania (Schimming et al. 2005). It turned out to dominate to an unusual extent in the alkaloid fraction beside seven minor congeners. Most of them were isomers of the main metabolite. All these metabolites were also present in unripe fruits and stems. However, they were not detectable in snch parts from another provenance (Ecnador) of this species (seeds not checked). 

In addition to a-amino acids, P- and y-amino acids can also be found in food. Naturally occurring P-alanine (3-aminopropionic add, 2-10) acts in the biosynthesis of pantothenic add, acetyl coenzyme A, other acyl coenzymes A (see Section 5.9.1) and some histidine dipeptides. P-Alanine is synthesised in several different ways, by aspartic add decarboxylation (in bacteria), but also by the transformation of propionic acid (in bacteria and some plants), by degradation of the polyamines spermine and spermidine (in yeasts and many plants, such as tomato, soybean and maize), or arising from the pytirnidine derivative uracil that occurs in aU animals and in some plants, such as wheat. 

MW -bis(benzyloxycarbonyl)diamine followed by hydrogenol-ysis of die Cbz groups furnishes the r-butoxycarbonylated derivative of the primary amino function (eq 24). Analogous strategies have been used for the selective indirect acylation of polyamines such as spermidine. ... 

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