In
chemistry a divergent synthesis is a strategy with the aim to improve the efficiency of
chemical synthesis
As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mod ...
. It is often an alternative to
convergent synthesis In chemistry a convergent synthesis is a strategy that aims to improve the efficiency of multistep synthesis, most often in organic synthesis. In this type of synthesis several individual pieces of a complex molecule are synthesized in stage one, ...
or linear synthesis.
In one strategy divergent synthesis aims to generate a
library
A library is a collection of materials, books or media that are accessible for use and not just for display purposes. A library provides physical (hard copies) or digital access (soft copies) materials, and may be a physical location or a vir ...
of
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s by first reacting a molecule with a set of reactants. The next generation of compounds is generated by further reactions with each compound in generation 1. This methodology quickly diverges to large numbers of new compounds
*A generates A1, A2, A3, A4, A5 in generation 1
*A1 generates A11, A12, A13 in generation 2 and so on.
An entire library of new chemical compounds, for instance
saccharide
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
s, can be screened for desirable properties. In another strategy divergent synthesis starts from a molecule as a central core from which successive generations of building blocks are added. A good example is the divergent synthesis of
dendrimer
Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The ...
s, for example, where in each generation a new monomer reacts to the growing surface of the sphere.
Diversity oriented synthesis
Diversity oriented synthesis or DOS is a strategy for quick access to molecule libraries with an emphasis on skeletal diversity. In one such application a
Petasis reaction
The Petasis reaction (alternatively called the Petasis borono–Mannich (PBM) reaction) is the multi-component reaction of an amine, a carbonyl, and a vinyl- or aryl-boronic acid to form substituted amines.
Reported in 1993 by Nicos Petasis ...
product (1) is functionalized with
propargyl bromide leading to a starting compound (2) having 5 functional groups. This molecule can be subjected to a range of reagents yielding unique molecular skeletons in one generation.
[''Path b to 3: cycloisomerization with Pd(PPh3)2(OAc)2. Path c to 4: ]enyne metathesis
An enyne metathesis is an organic reaction taking place between an alkyne and an alkene with a metal carbene catalyst forming a butadiene. This reaction is a variation of olefin metathesis.
The general scheme is given by ''scheme 1'':
:
When the ...
with Hoveyda–Grubbs catalyst
Grubbs catalysts are a series of transition metal carbene complexes used as catalysts for olefin metathesis. They are named after Robert H. Grubbs, the chemist who supervised their synthesis. Several generations of the catalyst have been develo ...
. Path d to 5: CpRu(CH3CN)3PF6 initiated +2 ycloaddition. Path e to 6: Alkyne hydrolysis with NaAuCl4 in MeOH. Path f to 7: Pauson–Khand reaction
The Pauson–Khand reaction (or PKR or PK-type reaction) is a chemical reaction described as a 2+2+1.html" ;"title="/nowiki>2+2+1">/nowiki>2+2+1/nowiki> cycloaddition between an alkyne, an alkene and carbon monoxide to form a α,β- cyclopentenon ...
with Co2(CO)8. Path g to 8: Esterification
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 ar ...
with sodium hydride
Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in co ...
. Path h to 9: Oxidation
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 ...
with mCPBA''
DOS Drugs
#Dosabulin
#Gemmacin B
#ML238
#
Robotnikinin
References
{{chemical synthesis
Chemical synthesis