The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine undergoes condensation with an aldehyde or ketone followed by ring closure. The reaction was first discovered in 1911 by Amé Pictet and Theodor Spengler. Traditionally an acidic catalyst in protic solvent was employed with heating, however the reaction has been shown to work in aprotic media in superior yields and sometimes without acid catalysis. The Pictet–Spengler reaction can be considered a special case of the Mannich reaction, which follows a similar reaction pathway. The driving force for this reaction is the electrophilicity of the iminium ion generated from the condensation of the aldehyde and amine under acid conditions. This explains the need for an acid catalyst in most cases, as the imine is not electrophilic enough for ring closure but the iminium ion is capable of undergoing the reaction.
The Zincke reaction is an organic reaction in which a pyridine is transformed into a pyridinium salt by reaction with 2,4-dinitro-chlorobenzene and a primary amine, named after Theodor Zincke.
In organic chemistry, the term organocatalysis refers to a form of catalysis, whereby the rate of a chemical reaction is increased by an organic catalyst referred to as an "organocatalyst" consisting of carbon, hydrogen, sulfur and other nonmetal elements found in organic compounds. Because of their similarity in composition and description, they are often mistaken as a misnomer for enzymes due to their comparable effects on reaction rates and forms of catalysis involved.
Zincke aldehydes, or 5-aminopenta-2,4-dienals, are the product of the reaction of a pyridinium salt with two equivalents of any secondary amine, followed by basic hydrolysis. Using secondary amines the Zincke reaction takes on a different shape forming Zincke aldehydes in which the pyridine ring is ring-opened with the terminal iminium group hydrolyzed to an aldehyde. The use of the dinitrophenyl group for pyridine activation was first reported by Theodor Zincke. The use of cyanogen bromide for pyridine activation was independently reported by W. König:
Spirotryprostatin B is an indolic alkaloid found in the Aspergillus fumigatus fungus that belongs to a class of naturally occurring 2,5-diketopiperazines. Spirotryprostatin B and several other indolic alkaloids have been found to have anti-mitotic properties, and as such they have become of great interest as anti-cancer drugs. Because of this, the total syntheses of these compounds is a major pursuit of organic chemists, and a number of different syntheses have been published in the chemical literature.
Spirotryprostatin A is an indolic alkaloid from the 2,5-Diketopiperazine class of natural products found in the Aspergillus fumigatus fungus. Spirotryprostatin A and several other indolic alkaloids have been found to have anti-mitotic properties, and as such they have become of great interest as anti-cancer drugs. Because of this, the total syntheses of these compounds is a major pursuit of organic chemists, and a number of different syntheses have been published in the chemical literature.
Asymmetric hydrogenation is a chemical reaction that adds two atoms of hydrogen preferentially to one of two faces of an unsaturated substrate molecule, such as an alkene or ketone. The selectivity derives from the manner that the substrate binds to the chiral catalysts. In jargon, this binding transmits spatial information from the catalyst to the target, favoring the product as a single enantiomer. This "enzyme-like selectivity" is applied to the synthesis of some commercial pharmaceutical agents and agrochemicals.
Kendomycin is an anticancer macrolide first isolated from Streptomyces violaceoruber. It has potent activity as an endothelin receptor antagonist and anti-osteoporosis agent. It also has strong cytotoxicity against various tumor cell lines.
Brevianamides are indole alkaloids that belong to a class of naturally occurring 2,5-diketopiperazines produced as secondary metabolites of fungi in the genus Penicillium and Aspergillus. Structurally similar to paraherquamides, they are a small class compounds that contain a bicyclo[2.2.2]diazoctane ring system. One of the major secondary metabolites in Penicillium spores, they are responsible for inflammatory response in lung cells.
Indole is an aromatic heterocyclic organic compound with formula C8H7N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin.
Palau'amine is a toxic alkaloid compound synthesized naturally by Stylotella agminata, a species of sea sponge found in the southwest Pacific Ocean. The name of the molecule derives from the island nation of Palau, near which the sponges are found.
2,5-Diketopiperazine, also known as piperazine-2,5-dione and as the cyclodipeptide cyclo(Gly-Gly), is an organic compound and the smallest cyclic dipeptide that consists of a six-membered ring containing two amide linkages where the two nitrogen atoms and the two carbonyls are at opposite positions in the ring. It was first synthesized by Curtius and Gloebel in 1888 and was the first compound containing a peptide bond to be studied by X-ray crystallography in 1938. It occurs in cocoa and bread and has a metallic and bitter taste.
Verruculogen is a mycotoxin produced by certain strains of aspergillus that belongs to a class of naturally occurring 2,5-diketopiperazines. It is an annulated analogue of cyclo(L-Trp-L-Pro) which belongs to the most abundant and structurally diverse class of tryptophan-proline 2,5-diketopiperazine natural products. It produces tremors in mice due to its neurotoxic properties. It also tested positive in a Salmonella/mammalian microsome assay and was shown to be genotoxic. It is a potent blocker of calcium-activated potassium channels.
Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group. It is found in the Apocynaceae family of plants including Picralima nitida, Vinca minor and the Aspidosperma.
Notoamides are bio-active isolates of marine Aspergillus.
(-)-Versicolamide B and (+)-Versicolamide B are spiroindole alkaloids isolated from the fungus Aspergillus that belong to a class of naturally occurring 2,5-diketopiperazines. The versicolamides are structurally complex spiro-cyclized versions of prenylated cyclo(L-Trp-L-Pro) derivatives which possess a unique spiro-fusion to a pyrrolidine at the 3-position of the oxindole core together with the bicyclo[2.2.2]diazaoctane ring system. While (-)-versicolamide B was isolated from the marine fungus Aspergillus sp. the enantiomer (+)-versicolamide B was isolated from the terrestrial fungi Aspergillus versicolor NRRL. The total asymmetric syntheses of both enantiomers have been achieved and the implications of their biosynthesis have been investigated.
Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the atropisomer of abyssomicin C. It is a spirotetronate that belongs to the class of tetronate antibiotics, which includes compounds such as tetronomycin, agglomerin, and chlorothricin. In 2006, the Nicolaou group discovered atrop-abyssomicin C while working on the total synthesis of abyssomicin C. Then in 2007, Süssmuth and co-workers isolated atrop-abyssomicin C from Verrucosispora maris AB-18-032, a marine actinomycete found in sediment of the Japanese sea. They found that atrop-abyssomicin C was the major metabolite produced by this strain, while abyssomicin C was a minor product. The molecule displays antibacterial activity by inhibiting the enzyme PabB, thereby depleting the biosynthesis of p-aminobenzoate.
Brevianamide F , also known as cyclo-(L-Trp-L-Pro), belongs to a class of naturally occurring 2,5-diketopiperazines. It is the simplest member and the biosynthetic precursor of a large family of biologically active prenylated tryptophan-proline 2,5-diketopiperazines that are produced by the fungi A.fumigates and Aspergillus sp. It has been isolated from the bacterium Streptomyces sp. strain TN58 and shown to possess activity against two Gram-positive bacteria, S.aureus and Micrococcus luteus, and has also been isolated from Bacillus cereus associated with the entomopathogenic nematode, Rhabditis (Oscheius) sp. and shown to have antifungal activity against T. rubrum, C. neoformans and C. albicans, better than amphotericin B. Although the proline 2,5-diketopiperazines are the most abundant and structurally diverse 2,5-diketopiperazines found in food, cyclo(L-Trp-L-Pro) has only been found as a minor 2,5-diketopiperazine (8.2ppm) in autolyzed yeast extract. Initially cyclo(L-Trp-L-Pro) and its DL, LD, and DD isomers showed potential for use in the treatment of cardiovascular dysfunction, however they were later shown to be hepatoxic.
Bicyclomycin (Bicozamycin) is a broad spectrum antibiotic active against Gram-negative bacteria and the Gram-positive bacterium, Micrococcus luteus that was isolated from Streptomyces sapporonesis and Streptomyces aizumenses in 1972. It belongs to a class of naturally occurring 2,5-diketopiperazines, that are among the most numerous of all the naturally occurring peptide antibiotics. This clinically useful antibiotic is rapidly absorbed in humans when given intramuscularly, has low toxicity and has been used to treat diarrhea in humans and bacterial diarrhea in calves and pigs.
In organometallic chemistry, the activation of cyclopropanes by transition metals is a research theme with implications for organic synthesis and homogeneous catalysis. Being highly strained, cyclopropanes are prone to oxidative addition to transition metal complexes. The resulting metallacycles are susceptible to a variety of reactions. These reactions are rare examples of C-C bond activation. The rarity of C-C activation processes has been attributed to Steric effects that protect C-C bonds. Furthermore, the directionality of C-C bonds as compared to C-H bonds makes orbital interaction with transition metals less favorable. Thermodynamically, C-C bond activation is more favored than C-H bond activation as the strength of a typical C-C bond is around 90 kcal per mole while the strength of a typical unactivated C-H bond is around 104 kcal per mole.
