Nitrogen-containing natural products

The ease with which amines are extracted into aqueous acid, combined with their regeneration on treatment with base, makes it a simple matter to separate amines from other plant materials, and nitrogen-containing natural products were among the earliest organic compounds to be studied. Their basic... 

Mannich reactions, or a mechanistic analog, are important in the biosynthesis of many nitrogen-containing natural products. As a result, the Mannich reaction has played an important role in the synthesis of such compounds, especially in syntheses patterned after the biosynthesis, i.e., biomimetic synthesis. The earliest example of the use of the Mannich reaction in this way was Sir Robert Robinson s successful synthesis of tropinone, a derivative of the alkaloid tropine, in 1917. 

Acyl nitroso compounds react with 1, 3-dienes as N-O heterodienophiles to produce cycloadducts, which have found use in the total synthesis of a number of nitrogen-containing natural products [21]. The cycloadducts of acyl nitroso compounds and 9,10-dimethylanthracene (4, Scheme 7.3) undergo thermal decomposition through retro-Diels-Alder reactions to produce acyl nitroso compounds under non-oxidative conditions and at relatively mild temperatures (40-100°C) [11-14]. Decomposition of these compounds provides a particularly clean method for the formation of acyl nitroso compounds. Photolysis or thermolysis of 3, 5-diphenyl-l, 2, 4-oxadiazole-4-oxide (5) generates the aromatic acyl nitroso compound (6) and ben-zonitrile (Scheme 7.3) [22, 23]. Other reactions that generate acyl nitroso compounds include the treatment of 5 with a nitrile oxide [24], the addition of N-methyl morpholine N-oxide to nitrile oxides and the decomposition of N, O-diacylated or alkylated N-hydroxyarylsulfonamides [25-29]. 

Scheme 4. Alkyne metathesis affording nitrogen-containing natural products or synthetic intermediates.

Alkaloids are a group of nitrogen-containing natural products that occur primarily in higher plants, although they are also found in some fungi, such as mushrooms. The name alkaloid (meaning alkali-like ) is applied because they are amines and thus basic. Their basic character allows them to be readily isolated from their plant source. The plant material is extracted with aqueous acid. This converts the alkaloid to an ammonium cation, which is water soluble. Neutralization of the acidic extract with base causes the alkaloid to precipitate. 

Dipolar cycloaddition of nitrones to alkenes has been widely utilized for the synthesis of many nitrogen-containing natural products. Indeed, in this process, up to three stereogenic centers are built up in a single step, often in a highly stereoselective manner. Louis and Hootele recently reported the first highly selective 1,3-dipolar cycloaddition between an a,P-unsaturated sulfoxide and a cyclic ni-... 

In 1851, A.W. Hofmann discovered that when trimethylpropylammonium hydroxide is heated, it decomposes to form a tertiary amine (trimethylamine), an olefin (propene), and water. Widespread use of this transformation did not occur until 1881, when Hofmann applied this method to the study of the structure of piperidines and nitrogen-containing natural products (e.g., alkaloids). " The pyrolytic degradation of quaternary ammonium hydroxides to give a tertiary amine, an olefin and water is known as the Hofmann elimination. The process involves three steps 1) exhaustive methylation of the primary, secondary or tertiary amine with excess methyl iodide to yield the... 

Synthetic methodology and total syntheses of nitrogen-containing natural products, such as the antibiotic 593A, /1-lactams, indole alkaloid vincadifformine, po-rothramycin B, vindolin, vinblastin 03YGK620. 

These nitrogen-containing natural products, often with powerful biological properties, are not usually incorporated into target molecules. However, they are important in asymmetric syntheses as the foundations of many reagents and catalysts. Quinine 119 is familiar as an anti-malarial and an ingredient in tonic water. Quinine and its twin cinchona alkaloid quinidine 118 are referred to as pseudo enantiomers. Each occurs naturally as one enantiomer only but the two structures are nearly enantiomeric only the vinyl side-chains disturb the symmetry and they act as enantiomers. The vinyl side-chains are reduced and two molecules of, say, dihydroquinine (DHQ) are joined... 

The diastereoselective hetero-Diels Alder reaction of imines leads to enantiomerically pure 2-substituted piperidines, important synthons for the synthesis of nitrogen-containing natural products. 2,3,4,6-Tetra-0-pivaloyl-/ -D-galactopyranosylimines 1, easily synthesized from the respective 1-galactosamine. react with isoprene (2a), 2,3-dimethyl-l,3-butadiene (2b) and ( )-l-methoxy-3-trimethylsiloxy-l,3-butadiene (4) under zinc chloride etherate catalysis71. Adducts 3 are obtained with moderate to good diastereoselectivities, while adduct 5 is produced with a diastereomeric ratio of greater than 95 5. Adduct 5 can then be converted into the alkaloid (S)-anabasin. 

Catalytic hydrogenation of unsaturated nitrogen heterocycles plays an important role in the synthesis of nitrogen-containing natural products such as alkaloids and amino acids. 

Besides the large group of alkaloids some nitrogen-containing natural products, do not fall under the definition of alkaloids, and are therefor discussed separately. 

The synthesis of nitrogen-containing natural products is also possible via diols such as these. Hudlicky and co-workers prepared the bicyclic alkaloid (+)-kifunensine, for example, from 284. 0 More complex molecules can also be prepared, as illustrated by the conversion of 285 into (+)-pancratistatin (291), via synthetic intermediate 290. Banwell et al. reported an asymmetric synthesis of (-)-patchoulenone from 287... 

Synthesis of nitrogen-containing natural products using allyl cyanate-to-isocyanate rearrangement 06Y96. 

Total Synthesis of Nitrogen-Containing Natural Products via Nitroso Diels-Alder Reaction... 

Reviewed here are contributions from our laboratories to the development of nitroso methodology for preparing nitrogen-containing natural products including alkaloids and a pheromone. 

In the area of nitrogen-containing natural products the following have been glycosylated the antitumor alkaloid 20(S)-camptothecin, the ergot alkaloids elymoclavine, chancoclavine, lysergol (en mic reaction), and castanospermine. ... 

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