Aflatoxin total synthesis concerns the

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

of a group of

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

s called

aflatoxin Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly '' Aspergillus'' species. The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, sweet ...

s. These compounds occur naturally in several

fungi A fungus (plural, : fungi or funguses) is any member of the group of Eukaryote, eukaryotic organisms that includes microorganisms such as yeasts and Mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified ...

. As with other chemical compound targets in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clay ...

, the organic synthesis of aflatoxins serves various purposes. Traditionally it served to prove the structure of a complex biocompound in addition to evidence obtained from spectroscopy. It also demonstrates new concepts in organic chemistry (reagents, reaction types) and opens the way to molecular derivatives not found in nature. And for practical purposes, a synthetic biocompound is a commercial alternative to isolating the compound from natural resources. Aflatoxins in particular add another dimension because it is suspected that they have been mass-produced in the past from biological sources as part of a

biological weapon A biological agent (also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon) is a bacterium, virus, protozoan, parasite, fungus, or toxin that can be used purposefully as a weapon in bioterroris ...

s program. The synthesis of racemic aflatoxin B1 has been reported by Buechi et al. in 1967 and that of racemic aflatoxin B2 by Roberts et al. in 1968 The group of

Barry Trost Barry M. Trost (born June 13, 1941, in Philadelphia) is an American chemist who is the Job and Gertrud Tamaki Professor Emeritus in the School of Humanities and Sciences at Stanford University. The Tsuji-Trost reaction and the Trost ligand are ...

of Stanford University is responsible for the

enantioselective In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

of (+)-Aflatoxin B₁ and B_2a in 2003. In 2005 the group of

E. J. Corey Elias James Corey (born July 12, 1928) is an American organic chemist. In 1990, he won the Nobel Prize in Chemistry "for his development of the theory and methodology of organic synthesis", specifically retrosynthetic analysis. Regarded by many a ...

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of high ...

presented the enantioselective synthesis of Aflatoxin B₂.Zhou, G.; Corey, E. J. "Short, Enantioselective Total Synthesis of Aflatoxin B₂ Using an Asymmetric +2Cycloaddition Step". ''J. Am. Chem. Soc.'' 2005, ''127'', 11958–11959.

Aflatoxin B2 synthesis

The total synthesis of Aflatoxin B2 is a multistep sequence that begins with a +3 ycloaddition between the

quinone The quinones are a class of organic compounds that are formally "derived from aromatic compounds benzene.html" ;"title="uch as benzene">uch as benzene or naphthalene] by conversion of an even number of –CH= groups into –C(=O)– groups with ...

1 and the

2,3-Dihydrofuran 2,3-Dihydrofuran is a heterocyclic compound. It is one of the simplest enol ethers and a position isomer of 2,5-dihydrofuran. It is a colorless volatile liquid. It undergoes lithiation upon treatment with butyl lithium Butyllithium may refer to ...

. This reaction is catalyzed by a

CBS catalyst The CBS catalyst or Corey–Bakshi–Shibata catalyst is an asymmetric catalyst derived from proline. It finds many uses in organic reactions such as the CBS reduction, Diels-Alder reactions and (3+2) cycloadditions. Proline, a natura ...

and is

. The next step is the orthoformylation of reaction product 2 in a

Duff reaction The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source. It is named after James Cooper Duff, who was a chemist at the Colle ...

. The

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...

group in 3 is

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

ified with

triflic anhydride Trifluoromethanesulfonic anhydride, also known as triflic anhydride, is the chemical compound with the formula (CF3SO2)2O. It is the acid anhydride derived from triflic acid. This compound is a strong electrophile, useful for introducing the trif ...

which adds a

triflate In organic chemistry, triflate ( systematic name: trifluoromethanesulfonate), is a functional group with the formula and structure . The triflate group is often represented by , as opposed to −Tf, which is the triflyl group, . For example, ...

protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...

. This step enables a

Grignard reaction The Grignard reaction () is an organometallic chemical reaction in which alkyl, allyl, vinyl, or aryl-magnesium halides ( Grignard reagent) is added to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of ...

of the

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...

group in 4 with methylmagnesiumbromide to the

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

5 which is then

oxidized Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a de ...

with the Dess-Martin periodinane to the

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

6. A Baeyer-Villiger oxidation converts the ketone to an

(7) and a reduction with Raney nickel converts the ester into an alcohol and removes the triflic acid group. In the final step the

coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by a lactone-like chain , forming a second six-membered ...

skeleton is added to 9 by a combined

coupling reaction A coupling reaction in organic chemistry is a general term for a variety of reactions where two fragments are joined together with the aid of a metal catalyst. In one important reaction type, a main group organometallic compound of the type R-M (R ...

with

zinc carbonate Zinc carbonate is the inorganic compound with the formula ZnCO3. It is a white solid that is insoluble in water. It exists in nature as the mineral smithsonite. It is prepared by treating cold solutions of zinc sulfate with potassium bicarbonate ...

of the

vinyl bromide Vinyl bromide is a simple vinyl halide. It is a colorless liquid. It is produced from ethylene dibromide. It is mainly used as a comonomer to confer fire retardant properties to acrylate polymers. Reactions and applications It reacts with ...

in 8 and a transesterification step between the phenol group and the ethyl ester group.

References

{{DEFAULTSORT:Aflatoxin Total Synthesis Total synthesis Aflatoxins