Endiandric acid c
Encyclopedia
Endiandric acid C, isolated from the Endiandra introsa tree, is a well characterized chemical compound
. People used the E. introsa tree for timber
, for its fruit
, drugs
, spices, perfume
oils, and leaves
. The Greek
s and Romans
made wreath
s for warrior
s and victorious athletes with E. intorsa leaves. Endiadric acid C is reported to have better antibiotic
activity than ampicillin
.
This genus of trees is in the family Lauraceae
. These trees are found in the north-eastern Australian rainforest
s and other tropical and subtropical regions. However, these trees are also found in southern Canada
and in Chile
. Endiandric acid C is also isolated from E. xanthocarpa species. Endiandric acids are also found in Beilschmiedia
trees, which were categorized under the Endiandra genus, but now forms its own genus as they found in cold, high latitude
areas, and even in New Zealand
. Other endiandric acids are found in the B. oligandra and B. anacardioides species, which are found in the Western Province of Cameroon
.
of Endiandrianic acid A-G compounds. Endiandric acid C was tested towards five strains of bacteria
, which included Bacillus subtilis
, Micococcus luteus, Streptococcus faecalis, Pseudomonas palida, and Escherichia coli
through examining zone inhibition and minimum concentration, which was found to range between 0.24 µg/mL and 500 µg/mL. Endiandric acid C has also been used to cure uterine tumors, rubella
, and female genital infections, and rheumatism
s.
s predicted when examining K. C. Nicolaou’s biomimetic synthesis of the endiandric acid cascade that enzymes aided this reaction
in the biosythesis. The biomimetic series determined that this process took place synthetically through a series of Diels-Alder cyclization reactions and therefore led researches to believe that Diels-Alderase assisted the formation of endiandric acid C.
Although it has been discovered since then that many famous cyclization reactions like that of Lovastatin
do result from the Diels-Alderase they have determine that the endiandric acid cascade does not involve enzymes but rather spontaneously undergoes ring formation from a derivative of bisnoryangonin 5, which results from both the shikimate
and acetic pathways. The 4-hydroxycinnamoyl-CoA, compound 2, is the precursor that comes from the shikimate pathway. Two units of malonyl CoA are then added to through the acetate pathway 3. Compound 3 is then reduced to the di-enol
form that tautomerizes to give the bisnoryangonin 5. A small amount of compound 5 can be isolated, however S-Adenosyl methionine
methylates most of it and gives yangonin
6. It has been proposed that a bisnoryangonin derivative 7, is then reduced by dehydrogenase
to give the polyene
precursor 8, that goes through spontaneous 8π conrotatory, 6π disrotatory, and [4+2] cyclization reactions to form endiandric acid C. This proposal is supported by the fact that endiandric acids naturally occur as racemic mixtures and not in an enantiomerically pure form, which should happen if enzymes mediate this process. The Diels-Alder reaction itself is a powerful reaction that can give cyclic compounds with many stereogenic centers.
s. They observe that the product looked like multiple endo-adducts resulting that came from several Diels-Alder reactions. They attempted to synthesize endiandric acid C from an acyclic symmetric diacetylenic diol precursor 14, which they hydrogenated using Lindlar catalyst
to give 15. Compound 15 then goes through intramolecular [4+2] cycloaddition
s, 6π disrotatory, and 8π conrotatory cyclization to give compound 17, bicyclic diol. They then silylated compound 17 and reacted it with sodium cyanide
and HMPA to give the cyanide intermediate 20, which was then hydrolyzed to the aldehyde
form 21. Condensation
of 21 gave the methyl ester
compound 22. They reacted the methyl ester with the same reagent as intermediate 17 to give the methyl ester form of compound 28. They then treated Compound 28 with a lithio derivative of diethyl cinnamylphosphonate at -78 degrees Celsius, in THF
for 15 minutes to give endiandric acid C 1.
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
. People used the E. introsa tree for timber
Timber
Timber may refer to:* Timber, a term common in the United Kingdom and Australia for wood materials * Timber, Oregon, an unincorporated community in the U.S...
, for its fruit
Fruit
In broad terms, a fruit is a structure of a plant that contains its seeds.The term has different meanings dependent on context. In non-technical usage, such as food preparation, fruit normally means the fleshy seed-associated structures of certain plants that are sweet and edible in the raw state,...
, drugs
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
, spices, perfume
Perfume
Perfume is a mixture of fragrant essential oils and/or aroma compounds, fixatives, and solvents used to give the human body, animals, objects, and living spaces "a pleasant scent"...
oils, and leaves
Leaves
-History:Vocalist Arnar Gudjonsson was formerly the guitarist with Mower, and he was joined by Hallur Hallsson , Arnar Ólafsson , Bjarni Grímsson , and Andri Ásgrímsson . Late in 2001 they played with Emiliana Torrini and drew early praise from the New York Times...
. The Greek
Ancient Greece
Ancient Greece is a civilization belonging to a period of Greek history that lasted from the Archaic period of the 8th to 6th centuries BC to the end of antiquity. Immediately following this period was the beginning of the Early Middle Ages and the Byzantine era. Included in Ancient Greece is the...
s and Romans
Ancient Rome
Ancient Rome was a thriving civilization that grew on the Italian Peninsula as early as the 8th century BC. Located along the Mediterranean Sea and centered on the city of Rome, it expanded to one of the largest empires in the ancient world....
made wreath
Wreath
A wreath is an assortment of flowers, leaves, fruits, twigs and/or various materials that is constructed to resemble a ring. They are used typically as Christmas decorations to symbolize the coming of Christ, also known as the Advent season in Christianity. They are also used as festive headdresses...
s for warrior
Warrior
A warrior is a person skilled in combat or warfare, especially within the context of a tribal or clan-based society that recognizes a separate warrior class.-Warrior classes in tribal culture:...
s and victorious athletes with E. intorsa leaves. Endiadric acid C is reported to have better antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
activity than ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
.
This genus of trees is in the family Lauraceae
Lauraceae
The Lauraceae or Laurel family comprises a group of flowering plants included in the order Laurales. The family contains about 55 genera and over 3500, perhaps as many as 4000, species world-wide, mostly from warm or tropical regions, especially Southeast Asia and South America...
. These trees are found in the north-eastern Australian rainforest
Rainforest
Rainforests are forests characterized by high rainfall, with definitions based on a minimum normal annual rainfall of 1750-2000 mm...
s and other tropical and subtropical regions. However, these trees are also found in southern Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
and in Chile
Chile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...
. Endiandric acid C is also isolated from E. xanthocarpa species. Endiandric acids are also found in Beilschmiedia
Beilschmiedia
Beilschmiedia is a genus of trees and shrubs in family Lauraceae. Most of its species grow in tropical climates, but a few of them are native to temperate regions, and they are widespread in tropical Asia, Africa, Madagascar, Australia, New Zealand, North America, Central America, the Caribbean,...
trees, which were categorized under the Endiandra genus, but now forms its own genus as they found in cold, high latitude
Latitude
In geography, the latitude of a location on the Earth is the angular distance of that location south or north of the Equator. The latitude is an angle, and is usually measured in degrees . The equator has a latitude of 0°, the North pole has a latitude of 90° north , and the South pole has a...
areas, and even in New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...
. Other endiandric acids are found in the B. oligandra and B. anacardioides species, which are found in the Western Province of Cameroon
Cameroon
Cameroon, officially the Republic of Cameroon , is a country in west Central Africa. It is bordered by Nigeria to the west; Chad to the northeast; the Central African Republic to the east; and Equatorial Guinea, Gabon, and the Republic of the Congo to the south. Cameroon's coastline lies on the...
.
Bioactivity
This compound has the best antibacterial activityAntibacterial activity
The shelf life of a product can be extended either by adding artificial preservatives or by taking hygienic measures during the manufacturing process. As the consumer trend today is towards preservative-free foods with a long shelf-life, industry is being forced to rethink its manufacturing methods...
of Endiandrianic acid A-G compounds. Endiandric acid C was tested towards five strains of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, which included Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...
, Micococcus luteus, Streptococcus faecalis, Pseudomonas palida, and Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
through examining zone inhibition and minimum concentration, which was found to range between 0.24 µg/mL and 500 µg/mL. Endiandric acid C has also been used to cure uterine tumors, rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
, and female genital infections, and rheumatism
Rheumatism
Rheumatism or rheumatic disorder is a non-specific term for medical problems affecting the joints and connective tissue. The study of, and therapeutic interventions in, such disorders is called rheumatology.-Terminology:...
s.
Biosynthesis
Many biochemistBiochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
s predicted when examining K. C. Nicolaou’s biomimetic synthesis of the endiandric acid cascade that enzymes aided this reaction
Reaction
Reaction may refer to:Response to another event*Adverse drug reaction*Chemical reaction*Emotional reaction*Light reaction*Nuclear reaction*TNA Reaction, a documentary show of TNA behind scenes.*Reaction , as defined by Newton's third law...
in the biosythesis. The biomimetic series determined that this process took place synthetically through a series of Diels-Alder cyclization reactions and therefore led researches to believe that Diels-Alderase assisted the formation of endiandric acid C.
Although it has been discovered since then that many famous cyclization reactions like that of Lovastatin
Lovastatin
Lovastatin is a member of the drug class of statins, used for lowering cholesterol in those with hypercholesterolemia and so preventing cardiovascular disease...
do result from the Diels-Alderase they have determine that the endiandric acid cascade does not involve enzymes but rather spontaneously undergoes ring formation from a derivative of bisnoryangonin 5, which results from both the shikimate
Shikimic acid
Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi , from which it was first isolated....
and acetic pathways. The 4-hydroxycinnamoyl-CoA, compound 2, is the precursor that comes from the shikimate pathway. Two units of malonyl CoA are then added to through the acetate pathway 3. Compound 3 is then reduced to the di-enol
Enol
Enols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...
form that tautomerizes to give the bisnoryangonin 5. A small amount of compound 5 can be isolated, however S-Adenosyl methionine
S-Adenosyl methionine
S-Adenosyl methionine is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate and methionine by methionine adenosyltransferase . Transmethylation, transsulfuration, and aminopropylation are the...
methylates most of it and gives yangonin
Yangonin
Yangonin is one of the six major kavalactones found in the kava plant.Yangonin displays marked in vitro toxicity on human hepatocytes with approximately 40% reduction in viability based on an ethidium bromide assay. The predominant mode of cell death turned out to be apoptosis rather than necrosis....
6. It has been proposed that a bisnoryangonin derivative 7, is then reduced by dehydrogenase
Dehydrogenase
A dehydrogenase is an enzyme that oxidises a substrate by a reduction reaction that transfers one or more hydrides to an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN.-Examples:...
to give the polyene
Polyene
Polyenes are poly-unsaturated organic compounds that contain one or more sequences of alternating double and single carbon-carbon bonds. These double carbon-carbon bonds interact in a process known as conjugation, which results in an overall lower energy state of the molecule.Organic compounds with...
precursor 8, that goes through spontaneous 8π conrotatory, 6π disrotatory, and [4+2] cyclization reactions to form endiandric acid C. This proposal is supported by the fact that endiandric acids naturally occur as racemic mixtures and not in an enantiomerically pure form, which should happen if enzymes mediate this process. The Diels-Alder reaction itself is a powerful reaction that can give cyclic compounds with many stereogenic centers.
Organic synthesis
K. C. Nicolaou’s group successfully synthesized compound 1, in 1982 using a series of sterocontrolled electrocyclic reactionElectrocyclic reaction
In organic chemistry, an electrocyclic reaction is a type of pericyclic rearrangement reaction where the net result is one pi bond being converted into one sigma bond or vice-versa...
s. They observe that the product looked like multiple endo-adducts resulting that came from several Diels-Alder reactions. They attempted to synthesize endiandric acid C from an acyclic symmetric diacetylenic diol precursor 14, which they hydrogenated using Lindlar catalyst
Lindlar catalyst
A Lindlar catalyst is a heterogeneous catalyst that consists of palladium deposited on calcium carbonate and treated with various forms of lead. The lead additive serves to deactivate the palladium sites. A variety of "catalyst poisons" have been used including lead acetate and lead oxide. The...
to give 15. Compound 15 then goes through intramolecular [4+2] cycloaddition
Cycloaddition
A cycloaddition is a pericyclic chemical reaction, in which "two or more unsaturated molecules combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity." The resulting reaction is a cyclization reaction.Cycloadditions are usually described by the...
s, 6π disrotatory, and 8π conrotatory cyclization to give compound 17, bicyclic diol. They then silylated compound 17 and reacted it with sodium cyanide
Sodium cyanide
Sodium cyanide is an inorganic compound with the formula NaCN. This highly toxic colorless salt is used mainly in gold mining but has other niche applications...
and HMPA to give the cyanide intermediate 20, which was then hydrolyzed to the aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
form 21. Condensation
Condensation
Condensation is the change of the physical state of matter from gaseous phase into liquid phase, and is the reverse of vaporization. When the transition happens from the gaseous phase into the solid phase directly, the change is called deposition....
of 21 gave the methyl ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
compound 22. They reacted the methyl ester with the same reagent as intermediate 17 to give the methyl ester form of compound 28. They then treated Compound 28 with a lithio derivative of diethyl cinnamylphosphonate at -78 degrees Celsius, in THF
ThF
Follicular B helper T cells , are antigen-experienced CD4+ T cells found in the B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5...
for 15 minutes to give endiandric acid C 1.