Reserpine

NPTEL Chemistry Principles of Organic Synthesis
Lecture 36
12.1 Reserpine
MeO
A
B
N 2
H H
C
3
N
D
15
H
MeO2C
20
16
H
O
19
OMe
O
OMe
OMe
Reserpine
OMe
It is found, with other alkaloids, in the roots of the plant genus Rauwolfia and used in the
treatment of some mental disorders as well as for the reduction of hypertension.
This lecture will focus on the Woodward total synthesis of reserpine (R. B. Woodward et
al. J. Am. Chem. Soc. 1956, 78, 2023; Tetrahedron 1958, 2, 1).
Joint initiative of IITs and IISc Funded by MHRD
Page 1 of 30
12.1.1 Retrosynthetic Analysis

The strategy was based on building five contiguous stereocentres into a decalin derivative
that could be opened to a monocyclic compound to form ring E (Scheme 1).
MeO
CHO
C
B
N
N
H H
D
H
MeO2C
NH2
N
H
MeO
MeO2C
MeO2C
E
OAc
OMe
E
O
Ar
OMe
O
H
+
H
CO2Me MeO2C
Scheme 1. Retrosynthetic Analysis
12.1.2 Total Synthesis
The Diels-Alder reaction can lead to the ring junction having cis stereochemistry
and the carboxyl group lie on the same side as the rings with respect to the ring
junction (i) (Scheme 2). This step fixes the stereochemistry at C15, C16 and C20 of
reserpine.
NaBH4 reduction of the less hindered of the two carbonyl groups of 2 can
provide 3 (ii). The epoxidation of the isolated double bond with mCPBA at the
less hindered side can afford 4 (iii) that could undergo dehydration to give the
lactone 5 (iv).
Page 2 of 30
DielsAlder
O
[4+ 2]
NaBH4
heat
i
reduction
ii
+
CO2H
O
1
OH
H
OH
H
CO2H
PhCO3H
H
CO2H
epoxidation
iii
H
O 4 CO2H
Ac2O-NaOAc
iv
O
O
MeO -MeOH
OMe
-H2O
vii
Al(O Pr)3
vi
O
O
H
5
O
Br
HO
OMe
O
9
11
10 O
NH2
OHC
N
H
MeO
MeO2C
xiii
NaBH4
N
H
MeO2C
MeO2C
..
N
H
OAc
OMe
Cl+
N
O
O PCl2
ii. CH2N2
OMe
CO2Me
12
xii
POCl3
N
H
H
MeO2C
15
OAc
i. HIO4
N
H
xiv
OH
H
HO
OMe
CO2Me
13
MeO
i. CH2N2
ii. Ac2O/pyridine
OMe iii. OsO

4
CO2H
xi
OAc
14
OH
Zn-AcOH
ix
OMe
Br
CrO3
MeO
CO
NBS
H2SO4
viii
MeO
OH
O
8
xv
OAc
OMe
MeO
MeO
OAc
OMe
CO2Me
16
H
+
N
..
N
H O
Cl2OP
H
MeO2C
17
N+
N
H
H
-POCl2OH
OAc
OMe
H
MeO2C
18
OAc
OMe
Page 3 of 30
MeO
MeO
MeO
N
N
H H
DCC
lactone formation
H
MeO2C
OH
xvi
OAc
OMe
OMe
20
NaBH4
N
H H
H+
xvii
H
HO2C
xviii
21 OMe
OH-
N
H H
19
epimerization
xix
BuCOOH
MeO
MeO
MeO
MeO
NaOMe/MeOH
N
H H
xx
MeO
acylation
N
H H
ONa
MeO2C
22
23
OMe
COCl
xxi
OMe
MeO
MeO
N
N
H H
N
H H
MeOH/CHCl3 (3:1)
(+)-CSA
H
O
OMe
O
MeO2C
OMe
(-)-Reserpine
OMe
H
O
OMe
O
MeO2C
OMe
(+)-Reserpine
OMe
OMe
OMe
Scheme 2. Total Synthesis
Page 4 of 30
Meerwein-Ponndorf-Verley reduction of 5 could convert the keto group into

hydroxyl that can displace on the carbonyl of the six membered lactone ring,
giving a five membered lactone, and the hydroxyl group so released can open the
epoxide ring to afford 6 (Scheme 3).
O-
H
O
O-
CO
H
O
O-
OH
Scheme 3
Dehydration of 6 can give -unsaturated carbonyl compound 7 that could undergo

conjugate addition at the less hindered -side with methoxide to give 8 (vi and vii).
NBS in acid could approach -side of 8 to give a brominium ion that could be opened
by water to give the biaxial bromo-alcohol 9 (viii) that could undergo mild oxidation
to afford 10 (ix).
Zn in AcOH can bring the reductive opening of both the lactone and the strained ether
of 10 to give 11 (x) (Scheme 4).
-
Zn:
2H+
O
CO2-
CO2H
O
O
Zn:
O-
H+
OH
Br
Scheme 4
Esterification of the carboxyl group using diazomethane, acetylation of the alcohol

group using Ac2O and dihydroxylation of the double bond can give 12 (xi) that could
undergo oxidative cleavage followed by esterification of the new carboxyl group with
diazomethane to give 13 (xii).
Page 5 of 30
Schiff base formation of 13 with 6-methoxytryptamine can give 14 that could be

converted into 15 by NaBH4 reduction of the imine double bond (xiii and xiv).
Treatment of 15 with POCl3 can bring ring closure as in the Bischler-Napieralski
synthesis of isoquinoline, providing an imminium salt 18 via 16 and 17 (xv), which
could be reduced using NaBH4 to give 19 (xvi).
Base hydrolysis of 19 can give 20 having free OH and COOH groups that could be
joined to give a lactone 21 using DCC (xvii and xviii). Epimerization of the less
stable 21 using t-butyric acid can give the required more stable 22 that could be
converted into (+)-reserpine by opening of the lactone with MeOH followed by
acylation using 3,4,5-trimethoxybenzoyl chloride. The (+)-reserpine could be
resolved using CSA in a 3:1 mixture of MeOH and CHCl3.
Page 6 of 30
Problems
A. Complete the following reactions.
O
CO2H
CO2H
PhCO3H
1.
CN
2.
CN
O
CH2N2
3.
N
H
CO2Me
N
Me
O
4.
Ph
N
H
CH2N2
H
CO2Me
OMe
Ph
Me
CN
5.
N
H
B.
+ CH2O + Me2NH
H
MeI
N
H
Explain the stereochemical principles of Diels-Alder reaction.
Text Books
R. O. C. Norman, J. M. Coxon, Principles of Organic Synthesis, CRC Press, London,
2009.
K. C. Nicolaou, E. J. Sorensen, Classics in Total Synthesis, VCH, Weinheim, 1996.
Page 7 of 30
Lecture 37
12.2 Penicillin V
O
PhO
HN
Me
Me
H CO2K
Penicillin V
N
Penicillins are produced from the mould Penicillium notatum, different strains produce
different penicillins. They owe their importance to their powerful effect on various
pathogenic organisms. This lecture will present Sheehan total synthesis of penicillin V (J.
Am. Chem. Soc. 1959, 81, 3089).

The synthetic strategy employed by Sheehan for penicillin synthesis is shown in Scheme
1.
O
R
O
PhO
X
Ring formation
+
HN
N
O
Me
Me
CO2H
HN
HO2C HN
Lactamization
Penicillin V
Me
Me
CO2H
H2N
+
CO2H RO C
2
NH2
CHO
Scheme 1
Page 8 of 30

12.2.2.1. Synthesis of (+)-Penicillamine
Scheme 2 shows the synthesis of (+)-penicillamine from (+)-valine.
O
CO2H
ClCH2COCl
NH2
HO2C
O
N
H
1
(+-)-Valine
Ac2O
Cl
HO2C
O
ii
H2S
iii
2
HO2C
HO2C
H2O
iv
SH
HCl, pyridine
N
H
NH2
SH
(+)-Penicillamine
Scheme 2. Synthesis of Penicillamine
N-Acylation of (+)-valine with -chloroacetyl chloride gives 1 (i) that undergoes

dehydrative cyclization with acetic anhydride to provide 2 (ii) by the elimination of
HCl followed by a proton shift (Scheme 3).
HO2C
HO2C
O
N
H
1
Cl
OH
N
Cl
Ac2O
-H2O
O
-HCl
O
N
O
O
N
2
Cl
Scheme 3
O
N
Page 9 of 30
The azlactone 2 can be cleaved by H2S and the resulting thiol could cyclize via
Michael-type addition to the -unsaturated acid to give thiazoline 3 (iii) (Scheme 4)
that could be opened in boiling water to afford 4 (iv). The N-acyl group of 4 could be
removed by acid hydrolysis to yield (+)-penicillamine (v) that could be resolved using
brucine to give the optically pure (+)-penicillamine.
O
HO2C
O
O
H2S:
OH
..
HS
S
3
2
Scheme 4
Page 10 of 30
12.2.2.2 Synthesis of PenicillinV

Scheme 5 describes the total synthesis of penicillin
V.
H CO H
2
HCO2Et-NH2-
ClCH2CO2CMe3
N
K+
5
Me3CO2C
ii
Me3CO2C
6
Cl H3N
N2H4
Me3CO2C
H
HN
HCl
iv
H CO2H
Cl
PhO
O
PhO
CHO
Me3CO2C
S
H
HN
8 H CO H
2
HCl/CH2Cl2
H
HN
H CO2H
vi
HN
HO2C
H
HN
11 H CO2H
O
HN
KOH
HO2C
vii
PhO
10
O
PhO
O
HN
Et3N
v
Me3CO2C
iii
O
-
NH3+Cl-
HS
PhO
H
H
HN
12
H CO2K
HN
DCC
S
DCC =
viii
N C N
H CO2K
Penicillin V
Scheme 5. Total Synthesis
Nucleophilic substitution of 5 with t-butyl chloroacetate gives 6 (Gabriels synthesis,

i) that undergoes cross Claisen condensation with ethyl formate to afford 7 (ii).
The intermediate 7 with penicillamine hydrochloride at room temperature in sodium

acetate buffer affords 8 as a mixture of four diastereomers via Schiff base formation
followed by cyclization with the imine double bond (Scheme 6). However, the
required 8 could be separated from the mixture of diastereomers.
Page 11 of 30
H CO H
2
O
HS
O
Me3O2C
N
7
Me3CO2C
O
CHO
NH2
-H2O
HS
O
Me3CO2C
N
H CO2H
O
S
H
HN
H CO2H
Scheme 6
The removal of the phthalimido group from 8 could be accomplished using

hydrazine to afford 9 as a salt in the presence of HCl in acetic acid (iv).
Acylation of the amino group of 9 in the presence of triethyl amine can give 10 (v)
that could be converted into 11 by acid hydrolysis of t-butyl ester in
dichloromethane at 0 oC (vi).
The intermediate 11 in the presence of KOH can give the potassium salt (vii) that
could be cyclized using DCC to give the potassium penicillinate (viii). Penicillin V
can be extracted after acidification with phosphoric acid which crystallizes from
aqueous solution at pH 6.8.
Page 12 of 30
Problems
A. How will you synthesize the following compounds?
OH
O
Camphor
Menthol
B. Predict the major products for the following reactions.

CO2H
1.
ClCH2COCl, Ac2O
NH2
Ph
OH
DCC
2.
CH2Cl2
3.
NH2 +
DCC
HO2C
CH2Cl2
O
i. NaN3, AcOH
4.
ii. PPh3
5.
NH
CO2Me
LiClO4
NaH
6.
O
Page 13 of 30
Text Books
2009.
Page 14 of 30
Lecture 38
12.3 Prostaglandins E2 and F2a
Prostaglandins are a series of closely related hormones that are derivatives of prostanoic
acid:
1
CO2H
10
Prostanoic acid
19
Parent skeleton of the prostaglandin family
Prostaglandins are present in many mammalian tissues at very low concentrations and
exhibit potent effects on various types of smooth muscle. They are of considerable
medical interest for the control of hypertension.
Prostaglandins E2 (PGE2) and F2a (PGF2) are two of the six primary prostaglandins. The
E series have a -hydroxy ketone structure in the ring and differ in the degree of
unsaturation in the side-chain, while F series have a -hydroxy group in the ring and
likewise differ in the extent of unsaturation in the side-chains.
OH
CO2H
HO
H OH
PGE2
CO2H
HO
H OH
PGF2
This lecture presents E. J. Coreys approach for the synthesis of PGE2 and PGF2a (J. Am.
Chem. Soc. 1969, 91, 5675; ibid 1971, 93, 1489; ibid 1972, 94, 8616).
Page 15 of 30
12.3.1 Retrosynthetic Analysis of PGF2a

Scheme 1 outlines the general features of Coreys strategy for PGF2a synthesis.
CO2-
Ph2P
+
Wittig reaction
OH
OH
CO2H
HO
H OH
Horner-Wadsworth
Emmons Reaction
THPO
H OTHP
THPO
PGF2
O
RO
HO
Iodolactonization
O
PO(OMe)2
Me
+
I
O
OR
O
AcO
RO
OR
AcO
HO
RO
RO
Cl
CN
+
O
Cl
CN
Scheme 1
Page 16 of 30

Scheme 2 presents the synthesis of PGE2 and PGF2a.
Thallium(I) cyclopentadiene 1, prepared from cyclopentadiene with TlSO4 and KOH

in water, could be alkylated using benzyl chloromethyl ether, which has the
advantage that subsequent debenzylation can be more easily accomplished
(i).
Page 17 of 30
Ph
_
Cl
Tl+
mCPBA
O
Ph
Ph
Ph
ii
3 O
NaHCO3
CH2Cl2
iii
4
O
O
O
Ph
NaOH, H2O
O
CO2H KI3, NaHCO3
CO2
iv
OH
i. Ac2O, Pyridine
O ii. Bu3SnH, AIBN,

PhH, heat
AcO
7
vi
Ph
H2O
HO
O
O
O
CrO3 .2Py
H2-Pd/C
OH
vii
AcO
CHO NaH, DME, RT

ix
AcO
P(OMe)2
O
CH2Cl2
viii
AcO
i. K2CO3, MeOH
ii. DHP, TsOH,
CH2Cl2
O
Zn(BH4)2, DME
DIBAL-H, PhCH3,
-60 oC
xii
xi
x
11
10
9
O
AcO
THPO
H OH
H OTHP
12
DHP =
O
OH
O
CO2Na
PPh3
DMSO
HO
CO2H
xiii
THPO
THPO
13
H OTHP
i. H2Cr2O7, PhH/H2O
ii. AcOH, H2O, 37 oC
H OTHP
14
xiv
O
CO2H
HO
H OH
PGF2a
xv
AcOH, H2O, 37 oC
HO
CO2H
HO
H OH
PGE2
Scheme 2
Page 18 of 30
Ph
The copper(II)-catalyzed [4:2] cycloaddition of 2 with 2-chloroacrylonitrile can give

15 that could be hydrolyzed using KOH in DMSO to afford 3 (Scheme 3) (ii).
Cl
O
H
CN
Ph
KOH,
Ph
H2O/DMSO
Ph
Cl
Cu(BF4)2, 0 oC
CN
15
Scheme 3
Baeyer-Villiger oxidation of the ketone 3 can give lactone 4 resulting from migration
of secondary carbon in preference to the primary carbon (iii).
The lactone 4 can be hydrolyzed with aqueous NaOH and the free acid 5 could be
obtained by neutralization with CO2 (iv). The latter could be iodolactonized with KI3
to afford 6 having five asymmetric centres (v).
Acetylation of the OH group employing acetic anhydride as an acylating agent

followed by deiodination using tributyltin hydride (Bu3SnH) in the presence of
radical initiator AIBN can give 7 (vi) that could be debenzylated by hydrogenolysis
to afford 8 (vii).
The PDC promoted alcohol oxidation of 8 can give the aldehydes 9 (viii) that could
undergo Wadsworth-Emmons reaction with the anion of dimethyl 2-oxoheptyl
phosphonate to give 10 (ix).
The Zn(BH4)2 mediated reduction of the carbonyl group of the side-chain can yield
11 (x). The protection of OH groups of 11 can be readily accomplished with DHP in
the presence of TsOH to afford 12 (xi).
The selective reduction of 11 to lactol 12 using DIBAL-H (xii) followed by Wittig

reaction on the masked aldehydes in DMSO with the phosphorus ylide can afford 13
(xiii).
The resultant prostanoid material 13 could be converted into prostaglandins E2 by

oxidation of the unprotected hydroxyl group followed by aqueous acidic hydrolysis
(xv), whilest the aqueous acid hydrolysis of 13 could afford F2(xiv).
Page 19 of 30
Problems
A.
Outline synthetic route for oleic acid.
B.
Complete the following.

O
1.
MCPBA
KBrO3
2.
CO2H H2SO4
Cs2CO3
3.
OH PhCH2Br
Br
O
4.
N
H
i. PPh3
CF2CF3
CHN2
5.
ii. base
Cu(II)
Text Books
2009.
Page 20 of 30
Lecture 39
12.4 Ibogamine
N
N
H
Ibogamine
Ibogamine is an alkaloid in the oboga family that has the clinically important antitumor
alkaloid vinblastine. Hence, efficient synthetic approaches for the construction of the
family of compounds have been stimulated. This section focuses on a short,
stereocontrolled synthesis of ibogamine (B. M. Trost et al., J. Am. Chem. Soc. 1978, 100,
3930).

Scheme 1 outlines the common featurs of Trosts strategy for ibogamine synthesis:
H
N
H
N
Electrophilic
Substitution
-Allyl
Substitution
N
N
H
Ibogamine
N
AcO
NH Reduction
AcO
N
H
Condensation
NH2
CHO
OAc
+
CHO
AcO
[4+2]
+
N
H
Scheme 1
Page 21 of 30
12.4.2 Synthesis of Ibogamine

The synthesis of ibogamine could be accomplished in five steps employing Diels-Alder
reaction as key step to control the stereochemistry (Scheme 2).
H
N
NH2
OAc
CHO
CHO
N
H
AcO
BF3OEt
[4+2]
Toluene, MeSO4
-10 oC ii
H
N
B. M. Trost et al., J. Am. Chem. Soc. 1978, 100, 3930.
NH
Pd(PPh3)4
AcO
iii
NaBH4, MeOH
AcO
N
o
CH3CN, 70 C
iv
4
N
H
AgBF4, CH3CN, 1 h
PdCl2(CH3CN)2, RT
NaBH4
v
N
N
H
Ibogamine
Scheme 2
The Diels-Alder reaction of diene 1 with acrolein could afford the six-membered
ring 2 having all the three substituents cis (i). Although, it is immaterial for the
acetoxy group, the cis relationship between the ethyl and aldehydes groups is
required to obtain the right stereochemistry of the target molecule.
The Schiff base formation of 2 with tryptamine can give 3 (ii) that could be
readily reduced using NaBH4 to afford 4 (iii).
The intermediate 4 may undergo reaction with Pd(0) to give -allylic complex
with a loss of acetate ion, that could react with the nucleophilic nitrogen atom of
the amino group to afford 5 (iv).
Page 22 of 30
The PdCl2 effected electrophilic substitution of the indole ring can give metal salt
complex (Scheme 3) that could be reduced using NaBH4 to afford the target
molecule (v). The presence of silver ion increases the reactivity of the process.
M
N
M
N
H
N
H
M = silver-palladium salt complex or partially ionized palladium salt

Scheme 3
Problems
Complete the following with major products.
NMe2
i. KCN, DMF
1.
ii. LiAlH4, THF
N
H
heat
2.
OTMS
3.
NO2
N
CO2Et
i. heat, ii. HCl. THF
+
NMe2
O
heat
N
4.
S
MgBr
5.
NO2
NH4Cl
Me
Page 23 of 30
Text Book
R. O. C. Norman and J. M. Coxon, Principles of Organic Synthesis, CRC Press, London,
2009.
Page 24 of 30
Lecture 40
12.5 Synthesis of Adenosine Triphosphate (ATP)
NH2
N
OH OH OH
HO
O
O
O
P
P
P
O
O
O
O
HO
N
N
OH
Adenosine Triphosphate (ATP)
ATP, in conjunction with its diphosphate, ADP, acts as a reversible phosphorylating

couple and energy store. For example, it is concerned with the supply of energy for
muscular contraction.
NH2
HO
OH OH
O
O
P
P
O
O
O
HO
N
N
OH
Adenosine Diphosphate (ADP)
Synthesis of -Chloro-2,3,5-Triacetyl-D-Ribofuranose
The synthesis of -chloro-2,3,5-triacetyl-D-ribofurance from D-ribose could be
accomplished in five steps (Scheme 1).
The selective reaction of the primary OH group of D-ribose with triphenylmethyl

chloride ensures the sugar to adopt the furanose ring 1 system (i) that could be
transformed into 3 via 2 by acetylation (ii) followed by removel of the
triphenylmethyl group of using hydrogenation (iii).
Page 25 of 30
Acetylation (iv) followed by SN2 reaction at the carbon next to the ring oxygen of
4 using HCl (v) give the target molecule.
CHO
OH
OH
OH
OH
D-Ribose
H
H
H
Ph3CCl
i
CHO
OH
OH
OH
OCPh3
H
H
H
Ph3C
O
Ac2O
O
OH
OH
HO
Ph3C
ii
OAc
OAc
AcO
2
iii
AcO
AcO
Cl
A. R. Todd et al, J
Chem. Soc. 1947,
1052.
O
AcO
HCl, Et2O
OAc
OAc
OAc
AcO
Ac2O
H2, Pd
HO
iv
OAc
OAc
AcO
3
4
-Chloro-2,3,5-Triacetyl-D-Ribofuranose
Scheme 1
Synthesis of denosine
Uric acid could also be converted into adenosine in five steps (Scheme 2).
NH2
AcO
N
HO
HN
POCl3
N
N
Cl
OH
HN
uric acid
H2N
Cl
OH
NH3
Cl
N
H
ii
AcO
AcO
iv
NH2
A. R. Todd et al., J.
Chem. Soc. 1948, 967.
N
HO
O
HO
H2, Pd/BaSO4
Hydrolysis
NH2
N
Cl
O
v
HO
OH
HO
OH
9
adenosine
Scheme 2
Uric acid could be converted into 6 by reaction with POCl3 (i) that could undergo
nuleophilic substitution selectively at 6-position with NH3 to afford 7 (ii).
Cl
OAc
N
N
OAc
iii
Cl
Cl
AcO
N
Cl
Cl
Page 26 of 30
Cl
Reaction of 7 with the chloro-furanoside gives 8, presumably as a result of the

formation of an acetoxonium ion followed by an SN2 reaction (iii) (Scheme 3).
AcO
O
AcO
Cl
N
H
H
AcO
O
O
AcO
AcO
O
AcO
OAc
Scheme 3
Hydrolysis of the acetyl groups of 8 (iv) followed by hydrogenolysis of the C-Cl

bonds of 9 (v) gives the target adenosine.
Synthesis of ATP
The synthesis of ATP can be accomplished in eight steps form the above synthesized
adenosine (Scheme 4).
The 2- and 3-hydroxyl groups of the furanose ring of adenosine could be protected
by the formation of ketal to afford ketal 10 (i).
Phosphorylation of 10 could be effected to give 11 at a low temperature and the

removal of HCl can be performed using pyridine as a solvent (ii).
Mild acid hydrolysis of 11 leads to the formation of 12 by removal of the one of

benzyl groups along with the isopropylidene group (iii). After removal of the acid as
barium sulfate, the product could be dissolved in alkali and precipitated as its silver
salt.
Phosphorylation of 12 in anhydrous CH3COOH can give 13 (iv) that could be

selectively debenzylated with N-methylmorpholine to afford 14 (v).
Treatment of 14 with AgNO3 can give 15 (vi) that could be phosphorylated in a

mixture of CH3CN and PhOH to afford 16 (vii).
Page 27 of 30
The four benzyl groups of 16 could be removed by hydrogenolysis and the target
product, ATP, can be precipitated as its barium salt, liberated with sulfuric acid, and
isolated as its acridinium salt (viii).
Ph
NH2
N
HO
O
HO
HO
Acetone, H+
Ph
ClPO(OCH2Ph)2
adenosine
NH2
O
+
Ag-O
O
P
O
Ph
O
P
O
ClPO(OCH2Ph)2
O
P
O
O
HO
N
N
OH
13
Ph
NH2
Ph
N
O
O
P
O
O
O
P
O
iv
O
-
11
NH2
Ph
HO OH
12
Ph
10
Ph
AgNO3
iii
O
O
P
O
Ph
0.1 N-H2SO4
ii
OH
NH2
AgNO3
N
N
Ag+ O
vi
O
P
O
NH2
Ph
O
O
P
O
N
O
Ph
Me
N+
HO
HO
OH
OH
15
14
NH2
Ph Ph
ClPO(OCH2Ph)2
vii
Ph
NH2
Ph
O
O O
O
O
O
O
P
P
P
O
O
O
N
O
N H2, Pd
N
HO
OH OH OH
O
O
O
P
P
P
O
O
O
N
O
viii
ATP
HO
OH
HO OH
16
A. D. Todd et al., J. Chem. Soc. 1947, 648; 1949, 582.
Scheme 4
Page 28 of 30
N
N
Preparation of Dibenzyl Chlorophosphonate

The chlorination of dibenzyl phosphate can give the phosphorylating agent, dibenzyl
chlorophosphonate, in carbon tetrachloride (Scheme 5).
2PhCH2OH +
H3PO3
HPO(OCH2Ph)2
Cl2
ClPO(OCH2Ph)2
Scheme 5
Problems
A. Provide synthetic routes for ADP and AMP.
NH2
NH2
OH OH
HO
O
O
P
P
O
O
N
O
N
N
OH
O
HO
P
O
N
O
HO
HO
OH
Adenosine Diphosphate (ADP)
N
N
OH
Adenosine Monophosphate (AMP)
Page 29 of 30
B. Complete the following reactions.

OH
Ph3CCl
1.
OH
OH
Ru(II)/O2
2.
OH
Pd/CaCO3/Pb
3.
CH2OH
H2
NaBH4, CeCl3
I
4.
O
O
Zn, TiCl4
5.
CH2Br2
SnMe3
Text Books
2009.
J. Clayden, N. Greeves, S. Warren, P. Wothers, Organic Chemistry, Oxford University
Press, New York, 2001.
Page 30 of 30

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Joint initiative of IITs and IISc Funded by MHRD

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