Pierre Jean Robiquet
Encyclopedia
Pierre Jean Robiquet was a French
chemist
, who laid founding work in identifying amino acid
s, the fundamental bricks of protein
s, through recognizing the first of them, asparagin, in 1806, in the take up of the industry of industrial dyes, with the identification of alizarin
in 1826, and in the emergence of modern medications, through the identification of codeine
in 1832, a powerful molecule today of widespread use with analgesic
and antidiarrheal properties.
Robiquet was born in Rennes
. He was at first a pharmacist in the French armies during the French Revolution
years and became a professor at the École de pharmacie in Paris
, where he died.(for biography details refer to the fr.wikipedia article)
Notable scientific achievements were among other things his isolation and characterization of properties of asparagine
(the first amino acid
to be identified, from asparagus
, in 1806, with Louis Nicolas Vauquelin
), cantharidin
(1810), the opium
alkaloid
narcotine (1817), caffeine
(1821), alizarin
(later on moved to mass industrial production by Carl Gräbe
and Carl Theodore Liebermann
in Germany, and by William Henry Perkin in Great Britain) and purpurin (1826), Orcin (1829), amygdalin
(1830), as well as codeine
(1832). Some of these discoveries were made in collaboration with other scientists. (for details on the conduct of these researches and discoveries refer to the fr.wikipedia article).
(1811), Deputy Professor in History of pharmaceutical matters (1811) then Professor (1814) then Administrator-Treasurer (1824) at the Ecole de Pharmacie now the Faculté de Pharmacie see [3] , member then Secretary General (1817) and President (1826) of the Société de Pharmacie later on known as Académie Nationale de Pharmacie see [8], member of the Académie de Médecine (1820), member of the Académie des Sciences (1833), one of the founders and first President of the Société de Prévoyance des Pharmaciens see [6](1820).
Distinguished with the order of the Légion d'Honneur
(1830).
Asparagin will turn out to be one of the 22 aminoacids that build-up all living matter on earth, the first ever identified and understood as belonging to a new class of molecules.
Progress in isolating the other aminoacids will be very slow, with less than a handful in total during the whole XIXth century.
For instance, the colour purple, which had been a mark of aristocracy and prestige since ancient times in Rome, the Middle East and Egypt, was especially expensive and difficult to produce—the dye used, known as Tyrian purple
, was made from the glandular mucus of certain molluscs. Its extraction was variable and complicated,and dependent on the availability of the very specific type of shell (actually two types, now known the one as Bolinus brandaris, and the other as Hexaplex trunculus
, nowadays classified within two different genders) from which it was extracted.
Another type of natural red dye used from times immemorial was obtained from madder
root in Central Asia
and Egypt
, where it was grown as early as 1500 BC. Cloth dyed with madder root pigment was found in the tomb of the Pharaoh
Tutankhamun
and in the ruins of Pompeii
and ancient Corinth. In the Middle Ages, Charlemagne
encouraged madder cultivation. It grew well in the sandy soils of the Netherlands
and became an important part of the local economy. By 1804, the English dye maker George Field had introduced new techniques known as lake
madder, that extended the use of the tincture to paints.
Robiquet obtained from madder root two distinct molecules with dye properties, the one producing a magnificent red, that he called alizarin
, which proved as well extremely stable, and another, of less stable properties, that he called purpurin.
Some 30 years later in April 1856, William Henry Perkin, then a mere youngster working as assistant at the Royal College of Chemistry in London within a team intent on research over the synthesis of quinine, a potent drug, discovered a process that obtained a purple dye (which he called mauveine
) from aniline
, which in turn could be easily obtained from coal tar
; over the next ten years Perkin set up the first industrial model of molecules obtained through synthesis from coal tar and his succes had prompted intense research from numerous teams all over Europe on coal tar by-products, while he himself pursued such a work on top of his industrial activity.
Thus it came that in 1868, in turn alizarin was proved to be obtainable from anthracene
, in parallel by Perkin and by Carl Gräbe
and Carl Theodore Liebermann
, both working in Germany for the BASF company; unfortunately Perkin missed the patent priority by one single day, alizarin's extraordinary properties made it become the first really mass industry-produced dye and enabled the rise of BASF to first rank in the chemistry industry world.
is probably Robiquet's most important contribution, that prevails still today with a very strong presence and impact on everyman's daily life; in effect, until the beginning of the 19th century, raw opium
was used in diverse preparations known as laudanum
(see Thomas de Quincey
's "Confessions of an English Opium-Eater
"), paregoric
elixirs (a number of them, very popular in England since the beginning of the 18th century), and health or even death hazards to users from improper preparation or improper use were frequent.
The isolation of codeine by Robiquet from opium's several active components while working on refined morphine
extraction processes, opened the path to the elaboration of a new generation of specific antitussive and antidiarrheal potions of much safer use, based on codeine only, which became immediately extremely popular.
Codeine is nowadays by far the most widely used opiate in the world and very likely even the most commonly used drug overall according to numerous reports over the years by organizations such as the World Health Organization
and its League of Nations
predecessor agency and others. It is one of the most effective orally-administered opioid analgesics and has a wide safety margin. It is from 8 to 12 percent of the strength of morphine in most people; differences in metabolism can change this figure as can other medications, depending on its route of administration.
While codeine can still be directly extracted from opium, its original source, most codeine is nowadays synthesized from morphine
through the process of O-methylation
.
s, starch
, a yellowish dye, a fraction with bitter taste, and, as from asparagi, a fraction that can be crystallized and seemingly close to asparagin, which it will be indeed proven to be in 1828 by Plisson.
Robiquet likewise analysed a variety of animal tissues. Thus in 1810, he isolated from Lytta vesicatoria, an insect, a molecule that he calls cantharidin
, which he proves is the cause of the severe irritations and blisters provoked by that insect, and is present in a variety of unrelated species that use the molecule as a protection of their eggs from predation [1] (Two families of insects belonging to the order of Coleoptera synthetise that molecule : Meloidae and Oedemeridae
. The first family, to the which Lytta vesicatoria belongs in the Lytta genus, is rich of several thousands of species)
In fact, even back into the days of the early classical period civilizations of the western Mediterrean, some types of flies from Spain had a reputation for inducing aphrodisiac effects when used in preparations after having been desiccated. Cantharidin has never been proven to provide such collateral benefits, whereas Robiquet demonstrated it had very definite toxic and poisonous properties comparable in degree to that of the most violent poisons known in the XIXth century, such as strychnine
.
This particular study, that demonstrated, as early as in 1810, the possibility to separate, using "energetic" methods, a simple "principle" that was the actual effective fraction of a traditional natural compound obtained by "soft" methods has been exemplary for the burgeoning community of chemists in the early 19th century, and will prompt very rapidly a flurry of similar attempts that will yield within a few decades an incredible number of molecules from an ever growing number of research groups throughout Europe, and soon in the trail, in the US.
In the frame of that same investigation, Robiquet in addition evidences the presence of uric acid
within insects feeding on plant tissues.
Over a period of some fifteen years, Pierre Robiquet will also conduct a series of investigations on bitter almonds oil, a complex substance obtained from Prunus dulcis. In 1816, together with Jean-Jacques Colin, they obtain a new component which they call "éther hydrochlorique", in effect 1,2-dichloroethane
, which they will try to promote as a reinvigorating medicine (a common pursuit in those days, as is shown by the early uses of mixture such as Coke
).
In 1830, together with Antoine Boutron-Charlard, Robiquet obtains a new molecule which he calls amygdalin
; this component presented strange properties and was actually the first glycoside
ever to be evidenced. This discovery was opening the door to the huge family of aromatic molecules, that are based on the cyclic 6 carbon benzenoic structure. In their various attempts at breaking down amygdalin in by-products, Robiquet and Boutron-Charlard obtained benzaldehyd but they failed in working out a proper interpretation of the structure of amygdalin that would account for it, and thus missed the identification of the benzoyl
radical C7H5O.
This last step was achieved some few months later (1832) by Friedrich Wöhler
and Justus Liebig, these two got somehow a bit unfairly all the credit for this breakthrough result that was opening an entirely new branch for the industry of chemicals with wide-ranging applications.
Amygdalin and related variant molecules have been used throughout the XIXth (under promotion e.g. by Ernst T. Krebs
) and 20th centuries as anti-cancer drugs, however with inconclusive results as to actual benefits, while it was demonstrated in 1972 in a study at the Sloan-Kettering Cancer Institute that amygdalin and a related product that was commercialized under the name of "laetrile" actually could produce occasionally poisoning symptoms in some patients, due to degradation "in corpore" that produced cyanide.
French people
The French are a nation that share a common French culture and speak the French language as a mother tongue. Historically, the French population are descended from peoples of Celtic, Latin and Germanic origin, and are today a mixture of several ethnic groups...
chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
, who laid founding work in identifying amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s, the fundamental bricks of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, through recognizing the first of them, asparagin, in 1806, in the take up of the industry of industrial dyes, with the identification of alizarin
Alizarin
Alizarin or 1,2-dihydroxyanthraquinone is an organic compound with formula that has been used throughout history as a prominent dye, originally derived from the roots of plants of the madder genus.Alizarin was used as a red dye for the English parliamentary "new model" army...
in 1826, and in the emergence of modern medications, through the identification of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
in 1832, a powerful molecule today of widespread use with analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and antidiarrheal properties.
Robiquet was born in Rennes
Rennes
Rennes is a city in the east of Brittany in northwestern France. Rennes is the capital of the region of Brittany, as well as the Ille-et-Vilaine department.-History:...
. He was at first a pharmacist in the French armies during the French Revolution
French Revolution
The French Revolution , sometimes distinguished as the 'Great French Revolution' , was a period of radical social and political upheaval in France and Europe. The absolute monarchy that had ruled France for centuries collapsed in three years...
years and became a professor at the École de pharmacie in Paris
Paris
Paris is the capital and largest city in France, situated on the river Seine, in northern France, at the heart of the Île-de-France region...
, where he died.(for biography details refer to the fr.wikipedia article)
Notable scientific achievements were among other things his isolation and characterization of properties of asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
(the first amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
to be identified, from asparagus
Asparagus
Asparagus officinalis is a spring vegetable, a flowering perennialplant species in the genus Asparagus. It was once classified in the lily family, like its Allium cousins, onions and garlic, but the Liliaceae have been split and the onion-like plants are now in the family Amaryllidaceae and...
, in 1806, with Louis Nicolas Vauquelin
Louis Nicolas Vauquelin
Nicolas Louis Vauquelin , was a French pharmacist and chemist.-Early life:Vauquelin was born at Saint-André-d'Hébertot in Normandy, France. His first acquaintance with chemistry was gained as laboratory assistant to an apothecary in Rouen , and after various vicissitudes he obtained an introduction...
), cantharidin
Cantharidin
Cantharidin, a type of terpenoid, is a poisonous chemical compound secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. The false blister beetles and cardinal beetles also have cantharidin.-History:...
(1810), the opium
Opium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
narcotine (1817), caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
(1821), alizarin
Alizarin
Alizarin or 1,2-dihydroxyanthraquinone is an organic compound with formula that has been used throughout history as a prominent dye, originally derived from the roots of plants of the madder genus.Alizarin was used as a red dye for the English parliamentary "new model" army...
(later on moved to mass industrial production by Carl Gräbe
Carl Gräbe
Carl Gräbe was a German chemist from Frankfurt am Main.Gräbe studied at a vocational high school in Frankfurt and Karlsruhe Polytechnic and in Heidelberg. Later he worked for the chemical company Meister Lucius und Brüning . He supervised the production of Fuchsine and researched violet colorants...
and Carl Theodore Liebermann
Carl Theodore Liebermann
Carl Theodore Liebermann was a German chemist and student of Adolf von Baeyer.-Life:Liebermann first studied at the University of Heidelberg where Robert Wilhelm Bunsen was teaching. He then joined the group of Adolf von Baeyer at the University of Berlin where he received his Ph.D...
in Germany, and by William Henry Perkin in Great Britain) and purpurin (1826), Orcin (1829), amygdalin
Amygdalin
Amygdalin , C20H27NO11, is a glycoside initially isolated from the seeds of the tree Prunus dulcis, also known as bitter almonds, by Pierre-Jean Robiquet...
(1830), as well as codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
(1832). Some of these discoveries were made in collaboration with other scientists. (for details on the conduct of these researches and discoveries refer to the fr.wikipedia article).
Academic titles and distinctions
Registered Pharmacist (1808), lecturer in chemistry at the Ecole PolytechniqueÉcole Polytechnique
The École Polytechnique is a state-run institution of higher education and research in Palaiseau, Essonne, France, near Paris. Polytechnique is renowned for its four year undergraduate/graduate Master's program...
(1811), Deputy Professor in History of pharmaceutical matters (1811) then Professor (1814) then Administrator-Treasurer (1824) at the Ecole de Pharmacie now the Faculté de Pharmacie see [3] , member then Secretary General (1817) and President (1826) of the Société de Pharmacie later on known as Académie Nationale de Pharmacie see [8], member of the Académie de Médecine (1820), member of the Académie des Sciences (1833), one of the founders and first President of the Société de Prévoyance des Pharmaciens see [6](1820).
Distinguished with the order of the Légion d'Honneur
Légion d'honneur
The Legion of Honour, or in full the National Order of the Legion of Honour is a French order established by Napoleon Bonaparte, First Consul of the Consulat which succeeded to the First Republic, on 19 May 1802...
(1830).
Discovery of asparagin, the first aminoacid ever identified
In the fall of 1805, Robiquet, then a young help working in the laboratory of Louis Nicolas Vauquelin, starts analyses, with what rudimentary methods were then available, with asparagus juice. After a number of operations he obtains a cristallized white matter, which he and Vauquelin will throroughly try to characterize in 1806 as day by day their attempts evidence this is some new "chemical principle" with hitherto unknown properties, nothing like well known mineral salts classically obtained in the XVIIIth century. Duly convinced this is something completely new, they call this matter "asparagin", after the asparagus plant they extracted it from.Asparagin will turn out to be one of the 22 aminoacids that build-up all living matter on earth, the first ever identified and understood as belonging to a new class of molecules.
Progress in isolating the other aminoacids will be very slow, with less than a handful in total during the whole XIXth century.
Discovery of alizarin and various dyes
Even until the middle of 19th century, all dyes used for colouring cloth were natural substances, many of which were expensive and labour-intensive to extract. Furthermore, many lacked stability through washing or exposure to sunlight,or fastness.For instance, the colour purple, which had been a mark of aristocracy and prestige since ancient times in Rome, the Middle East and Egypt, was especially expensive and difficult to produce—the dye used, known as Tyrian purple
Tyrian purple
Tyrian purple , also known as royal purple, imperial purple or imperial dye, is a purple-red natural dye, which is extracted from sea snails, and which was possibly first produced by the ancient Phoenicians...
, was made from the glandular mucus of certain molluscs. Its extraction was variable and complicated,and dependent on the availability of the very specific type of shell (actually two types, now known the one as Bolinus brandaris, and the other as Hexaplex trunculus
Hexaplex trunculus
Hexaplex trunculus is a medium-sized species of sea snail, a marine gastropod mollusk in the family Muricidae, the murex shells or rock snails....
, nowadays classified within two different genders) from which it was extracted.
Another type of natural red dye used from times immemorial was obtained from madder
Madder
Rubia is a genus of the madder family Rubiaceae, which contains about 60 species of perennial scrambling or climbing herbs and sub-shrubs native to the Old World, Africa, temperate Asia and America...
root in Central Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
, where it was grown as early as 1500 BC. Cloth dyed with madder root pigment was found in the tomb of the Pharaoh
Pharaoh
Pharaoh is a title used in many modern discussions of the ancient Egyptian rulers of all periods. The title originates in the term "pr-aa" which means "great house" and describes the royal palace...
Tutankhamun
Tutankhamun
Tutankhamun , Egyptian , ; approx. 1341 BC – 1323 BC) was an Egyptian pharaoh of the 18th dynasty , during the period of Egyptian history known as the New Kingdom...
and in the ruins of Pompeii
Pompeii
The city of Pompeii is a partially buried Roman town-city near modern Naples in the Italian region of Campania, in the territory of the comune of Pompei. Along with Herculaneum, Pompeii was destroyed and completely buried during a long catastrophic eruption of the volcano Mount Vesuvius spanning...
and ancient Corinth. In the Middle Ages, Charlemagne
Charlemagne
Charlemagne was King of the Franks from 768 and Emperor of the Romans from 800 to his death in 814. He expanded the Frankish kingdom into an empire that incorporated much of Western and Central Europe. During his reign, he conquered Italy and was crowned by Pope Leo III on 25 December 800...
encouraged madder cultivation. It grew well in the sandy soils of the Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
and became an important part of the local economy. By 1804, the English dye maker George Field had introduced new techniques known as lake
Lake pigment
A lake pigment is a pigment manufactured by precipitating a dye with an inert binder, usually a metallic salt. The word lake is a homonym of lake as body of water and does not refer to it....
madder, that extended the use of the tincture to paints.
Robiquet obtained from madder root two distinct molecules with dye properties, the one producing a magnificent red, that he called alizarin
Alizarin
Alizarin or 1,2-dihydroxyanthraquinone is an organic compound with formula that has been used throughout history as a prominent dye, originally derived from the roots of plants of the madder genus.Alizarin was used as a red dye for the English parliamentary "new model" army...
, which proved as well extremely stable, and another, of less stable properties, that he called purpurin.
Some 30 years later in April 1856, William Henry Perkin, then a mere youngster working as assistant at the Royal College of Chemistry in London within a team intent on research over the synthesis of quinine, a potent drug, discovered a process that obtained a purple dye (which he called mauveine
Mauveine
Mauveine, also known as aniline purple and Perkin's mauve, was the first synthetic organic chemical dye.Its chemical name is3-amino-2,±9-dimethyl-5-phenyl-7-phenazinium acetate...
) from aniline
Aniline
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...
, which in turn could be easily obtained from coal tar
Coal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...
; over the next ten years Perkin set up the first industrial model of molecules obtained through synthesis from coal tar and his succes had prompted intense research from numerous teams all over Europe on coal tar by-products, while he himself pursued such a work on top of his industrial activity.
Thus it came that in 1868, in turn alizarin was proved to be obtainable from anthracene
Anthracene
Anthracene is a solid polycyclic aromatic hydrocarbon consisting of three fused benzene rings. It is a component of coal-tar. Anthracene is used in the production of the red dye alizarin and other dyes...
, in parallel by Perkin and by Carl Gräbe
Carl Gräbe
Carl Gräbe was a German chemist from Frankfurt am Main.Gräbe studied at a vocational high school in Frankfurt and Karlsruhe Polytechnic and in Heidelberg. Later he worked for the chemical company Meister Lucius und Brüning . He supervised the production of Fuchsine and researched violet colorants...
and Carl Theodore Liebermann
Carl Theodore Liebermann
Carl Theodore Liebermann was a German chemist and student of Adolf von Baeyer.-Life:Liebermann first studied at the University of Heidelberg where Robert Wilhelm Bunsen was teaching. He then joined the group of Adolf von Baeyer at the University of Berlin where he received his Ph.D...
, both working in Germany for the BASF company; unfortunately Perkin missed the patent priority by one single day, alizarin's extraordinary properties made it become the first really mass industry-produced dye and enabled the rise of BASF to first rank in the chemistry industry world.
Discovery and industrialization of codeine, a safe morphine-derivable molecule with widespread applications
CodeineCodeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
is probably Robiquet's most important contribution, that prevails still today with a very strong presence and impact on everyman's daily life; in effect, until the beginning of the 19th century, raw opium
Opium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
was used in diverse preparations known as laudanum
Laudanum
Laudanum , also known as Tincture of Opium, is an alcoholic herbal preparation containing approximately 10% powdered opium by weight ....
(see Thomas de Quincey
Thomas de Quincey
Thomas Penson de Quincey was an English esssayist, best known for his Confessions of an English Opium-Eater .-Child and student:...
's "Confessions of an English Opium-Eater
Confessions of an English Opium-Eater
Confessions of an English Opium-Eater is an autobiographical account written by Thomas De Quincey, about his laudanum addiction and its effect on his life...
"), paregoric
Paregoric
Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...
elixirs (a number of them, very popular in England since the beginning of the 18th century), and health or even death hazards to users from improper preparation or improper use were frequent.
The isolation of codeine by Robiquet from opium's several active components while working on refined morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
extraction processes, opened the path to the elaboration of a new generation of specific antitussive and antidiarrheal potions of much safer use, based on codeine only, which became immediately extremely popular.
Codeine is nowadays by far the most widely used opiate in the world and very likely even the most commonly used drug overall according to numerous reports over the years by organizations such as the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
and its League of Nations
League of Nations
The League of Nations was an intergovernmental organization founded as a result of the Paris Peace Conference that ended the First World War. It was the first permanent international organization whose principal mission was to maintain world peace...
predecessor agency and others. It is one of the most effective orally-administered opioid analgesics and has a wide safety margin. It is from 8 to 12 percent of the strength of morphine in most people; differences in metabolism can change this figure as can other medications, depending on its route of administration.
While codeine can still be directly extracted from opium, its original source, most codeine is nowadays synthesized from morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
through the process of O-methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
.
Sundry researches in pharmacology; missing by a hair's breadth the identification of the benzoyl radical in 1830
Robiquet has analysed the chemical byproducts that could be obtained from a variety of plants: asparagus, madder root, as already mentioned, with the important associated discoveries, and also others, which mostly helped in consolidating the existence of some molecules in a wide range of plants. Thus, in 1809, Robiquet extracts from liquorice root a sweetish matter which he dubs glycyrrhizine, from Glycirrhiza, the denomination of the genus to which belongs liquorice. He also obtained an oily fraction (0,8%), small quantities of a matter with properties of a gum, albuminic substances, tanninTannin
A tannin is an astringent, bitter plant polyphenolic compound that binds to and precipitates proteins and various other organic compounds including amino acids and alkaloids.The term tannin refers to the use of...
s, starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
, a yellowish dye, a fraction with bitter taste, and, as from asparagi, a fraction that can be crystallized and seemingly close to asparagin, which it will be indeed proven to be in 1828 by Plisson.
Robiquet likewise analysed a variety of animal tissues. Thus in 1810, he isolated from Lytta vesicatoria, an insect, a molecule that he calls cantharidin
Cantharidin
Cantharidin, a type of terpenoid, is a poisonous chemical compound secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. The false blister beetles and cardinal beetles also have cantharidin.-History:...
, which he proves is the cause of the severe irritations and blisters provoked by that insect, and is present in a variety of unrelated species that use the molecule as a protection of their eggs from predation [1] (Two families of insects belonging to the order of Coleoptera synthetise that molecule : Meloidae and Oedemeridae
Oedemeridae
The family Oedemeridae is a cosmopolitan group of beetles commonly known as false blister beetles, though some recent authors have coined the name pollen-feeding beetles...
. The first family, to the which Lytta vesicatoria belongs in the Lytta genus, is rich of several thousands of species)
In fact, even back into the days of the early classical period civilizations of the western Mediterrean, some types of flies from Spain had a reputation for inducing aphrodisiac effects when used in preparations after having been desiccated. Cantharidin has never been proven to provide such collateral benefits, whereas Robiquet demonstrated it had very definite toxic and poisonous properties comparable in degree to that of the most violent poisons known in the XIXth century, such as strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
.
This particular study, that demonstrated, as early as in 1810, the possibility to separate, using "energetic" methods, a simple "principle" that was the actual effective fraction of a traditional natural compound obtained by "soft" methods has been exemplary for the burgeoning community of chemists in the early 19th century, and will prompt very rapidly a flurry of similar attempts that will yield within a few decades an incredible number of molecules from an ever growing number of research groups throughout Europe, and soon in the trail, in the US.
In the frame of that same investigation, Robiquet in addition evidences the presence of uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
within insects feeding on plant tissues.
Over a period of some fifteen years, Pierre Robiquet will also conduct a series of investigations on bitter almonds oil, a complex substance obtained from Prunus dulcis. In 1816, together with Jean-Jacques Colin, they obtain a new component which they call "éther hydrochlorique", in effect 1,2-dichloroethane
1,2-Dichloroethane
The chemical compound 1,2-dichloroethane, commonly known by its old name of ethylene dichloride , is a chlorinated hydrocarbon, mainly used to produce vinyl chloride monomer , the major precursor for PVC production. It is a colourless liquid with a chloroform-like odour...
, which they will try to promote as a reinvigorating medicine (a common pursuit in those days, as is shown by the early uses of mixture such as Coke
Coke
Coke may refer to:* Coca-Cola, a soft drink originally based on coca leaf extract** The Coca-Cola Company, makers of this drink** Cola, any soft drink similar to Coca-Cola** Soft drink, any non-alcoholic carbonated beverage* Coca, a plant...
).
In 1830, together with Antoine Boutron-Charlard, Robiquet obtains a new molecule which he calls amygdalin
Amygdalin
Amygdalin , C20H27NO11, is a glycoside initially isolated from the seeds of the tree Prunus dulcis, also known as bitter almonds, by Pierre-Jean Robiquet...
; this component presented strange properties and was actually the first glycoside
Glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme...
ever to be evidenced. This discovery was opening the door to the huge family of aromatic molecules, that are based on the cyclic 6 carbon benzenoic structure. In their various attempts at breaking down amygdalin in by-products, Robiquet and Boutron-Charlard obtained benzaldehyd but they failed in working out a proper interpretation of the structure of amygdalin that would account for it, and thus missed the identification of the benzoyl
Benzoyl
In organic chemistry, benzoyl is the acyl of benzoic acid, with structure C6H5CO-. It should not be confused with benzyl, which is the radical or ion formed from the removal of one of the methyl hydrogens of toluene...
radical C7H5O.
This last step was achieved some few months later (1832) by Friedrich Wöhler
Friedrich Wöhler
Friedrich Wöhler was a German chemist, best known for his synthesis of urea, but also the first to isolate several chemical elements.-Biography:He was born in Eschersheim, which belonged to aau...
and Justus Liebig, these two got somehow a bit unfairly all the credit for this breakthrough result that was opening an entirely new branch for the industry of chemicals with wide-ranging applications.
Amygdalin and related variant molecules have been used throughout the XIXth (under promotion e.g. by Ernst T. Krebs
Ernst T. Krebs
Ernst T. Krebs, Jr. was an American biochemist. He is known for promoting various substances as alternative cures for cancer, including pangamic acid and amygdalin. He also co-patented the semi-synthetic chemical compound closely related to amygdalin named Laetrile, which was also promoted as a...
) and 20th centuries as anti-cancer drugs, however with inconclusive results as to actual benefits, while it was demonstrated in 1972 in a study at the Sloan-Kettering Cancer Institute that amygdalin and a related product that was commercialized under the name of "laetrile" actually could produce occasionally poisoning symptoms in some patients, due to degradation "in corpore" that produced cyanide.
Main published works
- 1805 : Essai analytique des asperges Annales de chimie, 55 (1805), 152–171
- 1806 : La découverte d'un nouveau principe végétal dans le suc des asperges L.N.Vauquelin et P.J.Robiquet, Annales de Chimie, 57, p88–93.
- 1810 : Expériences sur les cantharides, Robiquet, Annales de Chimie, 1810, vol. 76, pp. 302–322.
- 1812 : Observations sur la nature du kermès, Robiquet, Annales de Chimie, 81 (1812), 317–331.
- 1816 : Recherches sur la nature de la matière huileuse des chimistes hollandais, Robiquet, Colin, Annales de Chimie et de Physique, 1816, vol. 1, pp. 337–45.
- 1817 : Observations sur le memoire de M. Sertuerner relatif à l’analyse de l’opium, Robiquet, Annales de Chimie et de Physique ,5 (1817), 275–278;
- 1822 : Nouvelles experiences sur l’huile volatile d’amandes ameres, Robiquet, Annales de Chimie et de Physique , 21 (1822), 250–255.
- 1826 : De l'emploi du bicarbonate de soude dans le traitement médical des calculs urinaires
- 1826 : Sur un nouveau principe immédiat des végétaux (l’alizarine) obtenu de la garance Robiquet, Colin ,Journal de pharmacie et des sciences accessoires, 12 (1826), 407–412
- 1827 : Nouvelles recherches sur la matière colorante de la garance, Robiquet, Colin, Annales de chimie et de physique, 34 (1827), 225–253
- 1829 : Essai analytique des lichens de l’orseille, Robiquet, Annales de chimie et de physique, 42 (1829), 236–257
- 1830 : Nouvelles expériences sur les amandes amères et sur l'huile volatile qu'elles fournissent Robiquet, Boutron-Charlard, Annales de chimie et de physique, 44 (1830), 352–382
- 1831 : Nouvelles expériences sur la semence de moutarde
- 1832 : Nouvelles observations sur les principaux produits de l’opium, P.J.Robiquet, Annales de chimie et de physique, 51 (1832), 225–267
- 1832 : Notice historique sur André Laugier (suivie d'une autre notice sur Auguste-Arthur Plisson)
Associated articles
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- LaudanumLaudanumLaudanum , also known as Tincture of Opium, is an alcoholic herbal preparation containing approximately 10% powdered opium by weight ....
- AlizarinAlizarinAlizarin or 1,2-dihydroxyanthraquinone is an organic compound with formula that has been used throughout history as a prominent dye, originally derived from the roots of plants of the madder genus.Alizarin was used as a red dye for the English parliamentary "new model" army...
- MadderMadderRubia is a genus of the madder family Rubiaceae, which contains about 60 species of perennial scrambling or climbing herbs and sub-shrubs native to the Old World, Africa, temperate Asia and America...
- CantharidinCantharidinCantharidin, a type of terpenoid, is a poisonous chemical compound secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. The false blister beetles and cardinal beetles also have cantharidin.-History:...
- Narcotine
- AsparagineAsparagineAsparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
- Purpurin
- CaffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
- AmygdalinAmygdalinAmygdalin , C20H27NO11, is a glycoside initially isolated from the seeds of the tree Prunus dulcis, also known as bitter almonds, by Pierre-Jean Robiquet...
- BenzoylBenzoylIn organic chemistry, benzoyl is the acyl of benzoic acid, with structure C6H5CO-. It should not be confused with benzyl, which is the radical or ion formed from the removal of one of the methyl hydrogens of toluene...
- Louis-Nicolas Vauquelin
- Antoine Boutron-Charlard
- Theodore Nicolas Gobley
- Carl GräbeCarl GräbeCarl Gräbe was a German chemist from Frankfurt am Main.Gräbe studied at a vocational high school in Frankfurt and Karlsruhe Polytechnic and in Heidelberg. Later he worked for the chemical company Meister Lucius und Brüning . He supervised the production of Fuchsine and researched violet colorants...
- Carl Theodore LiebermannCarl Theodore LiebermannCarl Theodore Liebermann was a German chemist and student of Adolf von Baeyer.-Life:Liebermann first studied at the University of Heidelberg where Robert Wilhelm Bunsen was teaching. He then joined the group of Adolf von Baeyer at the University of Berlin where he received his Ph.D...
- William Henry Perkin
- Pierre Joseph PelletierPierre Joseph PelletierPierre-Joseph Pelletier was a French chemist who did notable research on vegetable alkaloids, and was the co-discoverer of quinine and strychnine.- Further reading :...
- http://www.shp-asso.org/index.php?PAGE=pelletier "Joseph Pelletier (1788-1842)"
- Joseph Bienaimé CaventouJoseph Bienaimé CaventouJoseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...
- http://www.shp-asso.org/index.php?PAGE=caventou "Joseph-Bienaimé Caventou (1795-1877)"
- La Faculté de Pharmacie de Paris
Curiosity items about Pierre Robiquet at today's "École de Pharmacie" in Paris
The "Ecole de Pharmacie", nowadays the "Faculté de Pharmacie" (University of pharmaceutical sciences) of Paris , stands 4, avenue de l'Observatoire, Paris 5eme- portrait by Devouge, Salle des Actes; visit http://www.shp-asso.org/index.php?PAGE=salledesactes and go to portrait n°48
- One of the many figure head medallions that adorn the walls of the inner court of the building represents Pierre Robiquet (along with other famed pharmacists and chemists such as Chaptal, Houel, Fourcroy, Antoine de Jussieu, Caventou et Pelletier, Brongniart, Newton, Lavoisier, Berthollet, Dumas, Bernard...) (visit http://www.shp-asso.org/ Société d'Histoire de la Pharmacie and http://www.dicoland.com/.../les-medaillons-de-la-faculte-de-pharmacie-de-paris-4767 Les médaillons de la Faculté de Pharmacie de Paris)
External links to French Pharmacy and Pharmacy scientists history sites
- http://www.uprp.net/centre_fichier.asp?idliste=1 Origines de la "Société de Prévoyance des Pharmaciens"
- http://www.shp-asso.org/index.php?PAGE=robiquet La codéine : Pierre ROBIQUET (1780–1840)
- http://cat.inist.fr/?aModele=afficheN&cpsidt=15271599 La Création de l'Ecole de Pharmacie
- http://acadpharm.net/ Académie Nationale de Pharmacie