The document discusses methodology in organic synthesis, including examples of natural products. It describes convergent and divergent synthesis strategies. Convergent synthesis involves coupling molecular fragments through independent synthesis to improve reaction yields compared to linear synthesis. Divergent synthesis starts from a central core and generates a library of compounds through successive additions. Functional group interconversion and addition techniques are discussed to allow for disconnection of target molecules during retrosynthetic analysis.

1. Topic:-
Methodology in organic synthes

2. Examples
Natural products e.g.. steroids, prostaglandins, alkaloids
HO
HO
OH
CO2Me
H
N
N
Cl
15-Methyl PGF2α (prostaglandin) Epibatidine (South American frog
alkaloid
Organic synthesis is a special branch of chemical synthesis and is
concerned with the construction of organic compounds via organic
reactions
Alkaloid)

3.  Each step of a synthesis involves a chemical
reaction, and reagents and conditions for each
of these reactions must be designed to give an
adequate yield of pure product, with as little
work as possible
METHODOLOGY IN ORGANIC CHEMISTRY

4.  In chemistry a convergent synthesis is a strategy that aims to
improve the efficiency of multi-step chemical synthesis.
 In linear synthesis the overall yield quickly drops with each
reaction step
 A → B → C → D
 Suppose the yield is 50% for each reaction, the overall yield of D is
only 12.5%
from A.
Convergent synthesis

5.  Convergent synthesis is applied in the synthesis of
complex molecules and involve fragment coupling
and independent synthesis.
 In a convergent synthesis
 A → B (50%)
 C → D (50%)
B + D → E (25%)
 the overall yield of E (25%)
looks much better.

6. o An example of its use in total synthesis is the final step
(photochemical [2+2]cycloaddition) towards the compound
Biyouyanagin A:
o Proteins of up to 300 amino acids are produced by a
convergent approach using chemical ligation.
Examples:

7. In chemistry a divergent synthesis is a strategy with
the aim to improve the efficiency of chemical synthesis
In another strategy divergent synthesis starts from a
molecule as a central core from which successive
generations of building blocks are added.
Divergent synthesis
In one strategy divergent synthesis aims to generate a
library of chemical compounds by first reacting a
molecule with a set of reactants

8. o A good example is the divergent synthesis of
dendrimers.
oThe next generation of compounds is generated by
further reactions with each compound in generation 1.
o This methodology quickly diverges to large numbers of new
compounds
o A generates A1, A2, A3, A4, A5 in generation 1
o A1 generates A11, A12, A13 in generation 2 and so on

9. Schematic of divergent and convergent method synthesis of
dendrimers

10. Functional group interconversion
writing of one functional group for another so that
disconnection becomes possible to get a starting
material available in the market.
FGI is necessary for functional group protection.
.
-CH2OH
FGI
-COOet
-COOH -CN
FGI
C6H5COOH
FGI
C6H5CN

11. Functional group addition (FGA): acyclic or alicyclic saturated
hydrocarbons are usually unreactive. Disconnection of such
hydrocarbons are difficult because the hydrocarbon is a compound
having no functional group which is guiding signal for
disconnection.
H OH
FGA
CH3-CH2
-
+
+
OH
CH3CH2MgBr CH3CHO
FGA
NH2
NO2
FGA
FGI

12. This FGA is two types:
1. Type1: FGA to the TM first and DIX done which gives recognizable SE
2. Type2: DIX is done to target molecule first and then FGA to the SN so
that recognizable SE is possible.
O
H
O
COOet
FGA
O
-
COOet
+ CH3 +
TM
DIX
SN
CH3i
o
COOet
o
DIX
CH3
+
CH3I
FGAFGA
O COOet
O
-
SE
+
TM

13. Disconnection rules:
 1) Dix is done mainly adjacent to the functional group i:e especially –OH
and C=O.
CH3CH2-OH- CH2CHO CH3CHOH + CH2CHO(Synthons).
2) a c-c double bond may be converted to c(OH)-CH before dix if c=c
is a part of a conjugated system involving hetero atom.
.
+ -
CH2OH +
+ -
FGI

14. • 3) In a conjugated or non conjugated system the dix of = carbons of c=c
may also be done without adding H2O to c=c part.
• (CH3)2 C=CH CH3 (CH3)2 COH + CH2CH3
• 4) The branch point is to be disconnected to get unbranched C- synthons
which are more likely to be available.
• . . + CH2CH2CH3
• 5) It is better to DIX towords middle of the target molecule rather than
cutting off one or 2 carbon atoms from the end.
• CH3CH2CH2CH2CH2CH3 CH3CH2CH2 +CH2CH2CH3
+ -
- +
_ +

15. • 6) Branches may be disconnected from rings.
+
+
7) Symmetric target molecules may be DIX symmetrically:
+
- +
8) It is worth to disconnnect a c-c bond between two functional
groups separated by not more than 3 other carbons.
+
+ -

16. • C-C bond DIX should be according to fragmentations in target molecule
• The DIX should be done in such a way that the synthetic route will be as
short as possible.
• ONE GROUP DISCONNECTIONS: disconnection of target molecule aiming
one particular functional group i:e DIX in which involve only one functional
group is called one group disconnection.
+ +
Cl-
ALCL3

17. • TWO GROUP DISCONNECTIONS: when a target molecule contain two
functional groups and if DIX is done using the two together i:e using of one
functional group to help disconnection of another is called two group
disconnection.
CH3CH2-OH- CH2CHO CH3CHOH + CH2CHO(Synthons)
+ -
CH3CHO CH3CHO

18. NO 2 C
H
OH
C
H
CH2OH
NHCOCHCl 2
NO 2 C
H
OH
C
H
CH2OH
NH2
ClCOCHCl 2
NO 2 C
H
OH
CH2 NH2
CH2O
NO 2 C CH2 NH2
O
NO 2 C
O
CH3
C
O
CH3
NO 2
ClCOCH 3
ClCOCH 3
CH3COOH
D(-)chloramphenicol
disconnection
disconnection
disconnection
disconnection
disconnection
acetic acid
benzene
acetyl chloride
nitro benzene
acetophenone
acetyl chloride
FGI
Example of retrosynthetic analysis: