A mild, new synthesis of isoquinolines

The cardiac effects of cinchona bark were noted in academic medicine at the end of the 17th century. Quinine was used sporadically through the first half of the 18th century for cardiac problems and arrhythmia and it became a standard of cardiac therapy in the second half of the 19th century. Another alkaloid chemical called was discovered to be responsible for this beneficial cardiac effect. Quinidine, a compound produced from quinine, is still used in cardiology today, sold as a prescription drug for arrhythmia. The sales demand for this drug still generates the need for harvesting natural quinine bark today because scientists have been unsuccessful in synthesizing this chemical without utilizing the natural quinine found in cinchona bark.

The Total Synthesis of Quinine - Journal of the …

The one thing, which is known, is the Rabe hadn't considered the stereochemistry of quinine.

Synthesis of Quinine by Jenna Butler on Prezi

The genus Cinchona contains about forty species of trees. They grow 15-20 meters in height andproduce white, pink, or yellow flowers. All cinchonas are indigenous to the eastern slopes of theAmazonian area of the Andes, where they grow from 1,500-3,000 meters in elevation on eitherside of the equator (from Colombia to Bolivia). They can also be found in the northern part of theAndes (on the eastern slopes of the central and western ranges). They are now widely cultivatedin many tropical countries for their commercial value, although they are not indigenous to thoseareas.TRIBAL AND HERBAL MEDICINE USESCinchona, or quinine bark, is one of the rainforest's most famous plants and most important discoveries. Legend has it that the name came from the countess of Chinchon, the wife of a Peruvian viceroy, who was cured of a malarial type of fever by using the bark of the cinchona tree in 1638. It was supposedly introduced to European medicine in 1640 by the countess of Chinchon, even before botanists had identified and named the species of tree. Quinine bark was first advertised for sale in England in 1658, and was made official in the British Pharmacopoeia in 1677. Physicians gave credit to the drug and, because of its effectiveness with malaria, it was recognized officially even while the identity of the tree species remained unknown. Several years after the "Countess's powder" arrived in England, it arrived in Spain. There, quinine bark was used by the Jesuits very early in its history and due to the influence of the Company of Jesus, the newly named "Jesuit's powder" became known all over Europe. When the plant was finally botanically classified almost one hundred years later in 1737, botanists still named it after the countess for her contribution. Throughout the mid-1600s to mid-1800s quinine bark was the primary treatment for malaria and it evidenced remarkable results. It was also used for fever, indigestion, mouth and throat diseases, and cancer. Natural quinine bark is still employed in herbal medicine systems around the world today. In Brazilian herbal medicine quinine bark is considered a tonic, a digestive stimulant, and fever-reducer. It is used for anemia, indigestion, gastrointestinal disorders, general fatigue, fevers, malaria and as an appetite stimulant. Other folk remedies in South America cite quinine bark as a natural remedy for cancer (breast, glands, liver, mesentery, spleen), amebic infections, heart problems, colds, diarrhea, dysentery, dyspepsia, fevers, flu, hangover, lumbago, malaria, neuralgia, pneumonia, sciatica, typhoid, and varicose veins. In European herbal medicine the bark is considered antiprotozoal, antispasmodic, antimalarial, a bitter tonic, and a fever-reducer. There it is used as an appetite stimulant, for hair loss, alcoholism, liver, spleen, and gallbladder disorders; and to treat irregular heart beat, anemia, leg cramps, and fevers of all kinds. In the U.S., quinine bark is used as a tonic and digestive aid; to reduce heart palpitations and normalize heart functions; to stimulate digestion and appetite; for hemorrhoids, varicose veins, headaches, leg cramps, colds, flu, and indigestion; and for its astringent, bactericidal, and anesthetic actions in various other conditions. PLANT CHEMICALS In 1820 two scientists, Pelletier and Caventou, isolated an alkaloid chemical in the bark which provided the highest antimalarial effect and named it . Once discovered, methods were developed to extract only the quinine alkaloid from the natural bark to sell as an antimalarial drug. The South American rainforests benefited from the income generated by harvesting cinchona bark for the extraction of this alkaloid from the bark for the manufacture of quinine drugs. In the middle of the 19th century, though, seeds of and were smuggled out of South America by the British and the Dutch. The species was planted and cultivated in Java by the Dutch and the species was cultivated in India and Ceylon by the British. However, the quinine content of these species was too low for high-grade, cost effective, commercial production of quinine. The Dutch then smuggled seeds of out of Bolivia, paying $20 for a pound of seeds, and soon established extensive plantations of quinine-rich cinchona trees in Java. They quickly dominated the world production of quinine and, by 1918, the majority of the world's supply of quinine was under the total control of the Dutch "kina burea" in Amsterdam. Huge profits were reaped - but Bolivia and Peru, from whence the resource originated, saw none of it.The upheavals of the Second World War led to changes in the market which still remain in effect today. When Java was occupied by the Japanese in 1942, the Allies' supply of quinine was cut off. South American sources of cinchona trees and quinine bark were once again in demand, but new plantations were planted by the Allies in Africa as well. This dire shortage of quinine fueled research for developing and producing a synthetic version of the quinine alkaloid rather than relying on the natural bark. In 1944 scientists were able to synthesize the quinine alkaloid in the laboratory. This led to various synthesized and patented quinine drugs which were manufactured by several pharmaceutical companies and which were of course, highly profitable. Today, Indonesia and India still cultivate cinchona trees; however Africa, with their expansions of the old WWII plantations, has emerged as the leading supplier of quinine bark. Much lower on the list of producers are the South American countries of Peru, Bolivia, and Ecuador, still struggling to compete. Although all cinchona species are good sources of quinine, and are the species containing the highest amount of quinine alkaloids - which is why they are the species of choice for cultivation today.The cardiac effects of cinchona bark were noted in academic medicine at the end of the 17th century. Quinine was used sporadically through the first half of the 18th century for cardiac problems and arrhythmia and it became a standard of cardiac therapy in the second half of the 19th century. Another alkaloid chemical called was discovered to be responsible for this beneficial cardiac effect. Quinidine, a compound produced from quinine, is still used in cardiology today, sold as a prescription drug for arrhythmia. The sales demand for this drug still generates the need for harvesting natural quinine bark today because scientists have been unsuccessful in synthesizing this chemical without utilizing the natural quinine found in cinchona bark.The main plant chemicals found in quinine bark include: aricine, caffeic acid, cinchofulvic acid, cincholic acid, cinchonain, cinchonidine, cinchonine, cinchophyllamine, cinchotannic acid, cinchotine, conquinamine, cuscamidine, cuscamine, cusconidine, cusconine, epicatechin, javanine, paricine, proanthocyanidins, quinacimine, quinamine, quinic acid, quinicine, quinine, quininidine, quinovic acid, quinovin, and sucirubine.

Quinine synthesis mystery solved | News | Chemistry …

The upheavals of the Second World War led to changes in the market which still remain in effect today. When Java was occupied by the Japanese in 1942, the Allies' supply of quinine was cut off. South American sources of cinchona trees and quinine bark were once again in demand, but new plantations were planted by the Allies in Africa as well. This dire shortage of quinine fueled research for developing and producing a synthetic version of the quinine alkaloid rather than relying on the natural bark. In 1944 scientists were able to synthesize the quinine alkaloid in the laboratory. This led to various synthesized and patented quinine drugs which were manufactured by several pharmaceutical companies and which were of course, highly profitable. Today, Indonesia and India still cultivate cinchona trees; however Africa, with their expansions of the old WWII plantations, has emerged as the leading supplier of quinine bark. Much lower on the list of producers are the South American countries of Peru, Bolivia, and Ecuador, still struggling to compete. Although all cinchona species are good sources of quinine, and are the species containing the highest amount of quinine alkaloids - which is why they are the species of choice for cultivation today.

The first entirely stereoselective total synthesis of (−)-quinine is reported.
T1 - Synthesis and biological activity of fatty acid derivatives of quinine

Total synthesis of quinine and quinidine. I.

The main plant chemicals found in quinine bark include: aricine, caffeic acid, cinchofulvic acid, cincholic acid, cinchonain, cinchonidine, cinchonine, cinchophyllamine, cinchotannic acid, cinchotine, conquinamine, cuscamidine, cuscamine, cusconidine, cusconine, epicatechin, javanine, paricine, proanthocyanidins, quinacimine, quinamine, quinic acid, quinicine, quinine, quininidine, quinovic acid, quinovin, and sucirubine.

The synthesis of quinine and its naturally occurring diastereomers from quinotoxine

Quinine For Resolution Of Racemates For Synthesis | …

A recent use for quinine drugs has been for the treatment of muscle spasms and leg cramps. A 1998 study documented the beneficial effects of quinine for leg cramps, with tinnitus being the only documented side effect. In 2002, a double-blind placebo study was undertaken in which 98 people with nocturnal leg cramps were given 400 mg of quinine daily for 2 weeks. The results stated that quinine administered at this dose effectively reduced the frequency, intensity, and pain of leg cramps without relevant side-effects. This use has fueled the natural product market and more people are looking for natural quinine bark as an alternative to the synthesized prescription drugs for this purpose.

They just used Rabe's start and finished the process off and therefore producing the first synthetic quinine.

Total synthesis of Quinine: - UW-Madison Chemistry