Purines imidazoles

Indole and isoquinoline alkaloids continue to play a dominant role. The apor-phinoids, comprising proaporphines, aporphines and related dimers, are treated separately, partly in order to reduce the burden on contributors aristolactams and aristolochic acids, which have not been reviewed since 1961, also are discussed in this chapter. This year the quinolizidine alkaloids, including the sesquiterpenoid Nuphar bases and the appropriate Lythraceae alkaloids, as well as azaphenalenes of plant and insect origin are reviewed together. Amaryllidaceae, Erythrina, imidazole, purine and peptide alkaloids are omitted from this volume, but it is expected that the chemistry of these groups covering the period 1974—1976 will be surveyed in Volume 7. 

Quinoline, indole, imidazole, purine, and pyrimidine are other examples of heterocyclic aromatic compounds. The heterocyclic compounds discussed in this section are examined in greater detail in Chapter 21. 

Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

Pyrazolines Imidazoles Thiazoles Oxadiazoles 1 -Phenylpyrazoles Purines Dioxolanes Ox azolines 10% Cyanethylated mannite on Celite 545. 5% OV-17 on Chromosorb W, AW-DMCS (H.P.). Carbowax 4000, dioleate on firebrick, 190 °C. Silicone grease on Chromosorb P. Apiezon L on firebrick C-22, 220 °C. 15% Hallcomid M-18 on firebrick. Carbowax 20M on Gas-Chrom P. Ethyleneglycol succinate on Diatoport-S. 

The THP derivative of the imidazole nitrogen in purines has been prepared by treatment with dihydropyran (TsOH, 55°, 1.5 h, 50-85% yield). It is cleaved by acid hydrolysis. ... 

The pyrimidine ring system is planar, while the purine system deviates somewhat from planarity in having a slight pucker between its imidazole and pyrimidine portions. Both are relatively insoluble in water, as might be expected from their pronounced aromatic character. 

Substitution of somewhat more complex side chains on the imidazole nitrogen of the purines leads to CNS stimulant drugs that have also been used as vasodilators and antispasmodic agents. Thus, alkylation of theophyline (2) with ethyl bromoacetate followed by saponification of the product gives acephylline (9). Alkylation with l-bromo-2-chloroethane gives the 2-chloroethyl derivative (10). Reaction of that intermediate with amphetamine yields fenethylline (11). ... 

Substitution of more complex acids for formic acid in the last step of the purine synthesis will afford intermediates substituted on the imidazole carbon atom. Thus, condensation of diaminouracyl, 12, with phenylacetic acid gives the benzylated... 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Hiickel 4n -r 2 rule and, 523-524 imidazole and, 529 Indole and. 533 ions and,525-527 isoquinoline and, 533 naphthalene and, 532 polycyclic aromatic compounds and,531-532 purine and, 533... 

Although purine nucleosides can frequently be halogenated at the vacant imidazole carbon (see above), AMialogenosuccinimides in acetic acid tend to promote intramolecular cyclizations instead. It has been demonstrated that 2-bromoadenosine is not an intermediate in this process (Scheme 55), which is believed to involve initial attack by positive halogen at N-3. 

H-Purin und 6-Amino-purin (unter Ammoniak-Abspaltung) liefern in waBrigen Puf-ferlosungen an Quecksilber l,2,3,6-Tetrahydro-9H-purin, das zu 5-Amino-4-(hydroxy-methylamino-methyl)-imidazol hydrolysiert werden kann2. 

The cyclization of o-substituted amides 206 was used for the preparation of a series of purine derivatives 207. In this case, the amine behaved as a nucleophile toward the amide function followed by ring closure to the imidazole ring (Scheme 75) [133]. 

P212121 Z — 8 Dx= 1.57 R = 0.085 for 1,743 intensities. The two independent molecules have similar conformations. The glycosyl dispositions are anti (90.1°, 91.2°), and the D-ribosyl groups are 3T4 (24.0°, 34.1° 15.6°, 35.5°). The exocyclic, C-4 -C-5 bond orientations are gauche+ (63.1°, 53.8°). The orientation of the methyl groups in both molecules is such that it is directed away from the imidazole moiety of the base, that is, the 0-6-C-7 bond is trans to the C-5-C-6 bond this arrangement constitutes an obstacle to formation of Watson-Crick hydrogen-bonds to the complementary base cytosine. In molecule A, 0-6 and C-7 are displaced from the purine plane by 79 and 87 pm, and, in molecule B, by 49 and 16 pm. The bases are stacked. 

This procedure provides a convenient synthesis of aminomalononitrile, which has been demonstrated to be a useful intermediate for the preparation of substituted imidazoles, thiazoles, oxazoles, purines, and purine-related heterocycles.2 It is also a convenient starting material for the preparation of diamino-maleonitrile.2, 4... 

This section is divided into eight subsections, covering imidazoles, pyrazoles, isoxazoles, oxazoles, triazoles, tetrazoles, pyridines, and pyrimidines, purines, and nucleic acid bases respectively. 

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