Laxmi GenChem Chemistry Presentation

Welcome
To
Laxmi GenChem
-Solution for Healthier Life
1
-

2e-mail: vijayreddy@laxmigenchem.com www.Laxmigenchem.com
ManagementManagement
Laxmi GenChem
Mr. Vijaya Madhava Reddy.V is Business Director of Laxmi
GenChem Pharma Ltd completed M.Sc in Organic Chemistry from
Osmania University and had 13 years Industrial Experience in
Synthetic Chemistry and Project Management in CRO & API area in
various MNC’s in Hyderabad. Mr. Reddy was also a former Research
Student from Masaryk University, Czech Republic, Europe.
Mr. Jagan Mohan.G is Managing Director of Laxmi GenChem Phama
Ltd completed M.Sc in Organic Chemistry and had 12 years Industrial
Experience in Synthetic Chemistry , CRAMS, Medicinal Chemistry &
API area in various MNC’s in Hyderabad. Mr. Jagan led Laxmi
GenChem through the initial phases of evolution with remarkable
success. He is responsible for putting the right scientific talent,
leadership, processes and infrastructure in place to ensure
continuous growth.

Over ViewOver View
 Laxmi GenChem is a dynamic custom synthesis and contract research organization
to support globally located pharmaceutical / biotech companies.
 We combine Science, Innovation and People to help our clients address their drug
development challenges.
 New frontiers require new ways of working and we believe that to deliver the true
promise of science, innovation is necessary.
 Our customers benefit not just from lower costs and boosted efficiencies, but also
from the infusion of fresh ideas and thinking.
3e-mail: vijayreddy@laxmgenchem.com www.Laxmi GenChem.com
Laxmi GenChem

Vision & MissionVision & Mission
 Laxmi GenChem would be a global leader in pharma services.
 Deliver value-added scientific services with speed and quality.
 Customer Focus - Change expected to exceptional. Customer once client forever.
 Strive to exceed expectations through innovative solutions.
 Committed to business and scientific integrity.
 Open, Fair, Honest and Transparent behavior.
 Give to get, give before you expect.
 Respect for individuals, property and timelines.
 Commit to Excel - In every act and deed Best always.
 Relentlessly and continuously improve ourselves and our solutions.
 Teamwork and Leadership Work Together…Win Together. A collective effort to be the leader in the
chosen field
Laxmi GenChem

Why Laxmi GenChem?Why Laxmi GenChem?
 Product Design & Development.
 Highly professional and experienced research team.
 Outstanding skills on difficult chemistry.
 Cost-effective services.
 On -time delivery Projects.
 Timely Communicative (Weekly Reports & Tele Conference).
 Data Base Management & Project Management
 Flexible for customer: we operate as your own chemistry department.
Laxmi GenChem

Research & Development CapabilitiesResearch & Development Capabilities
 Synthesis of Medicinal chemistry Analogs, Libraries & Scaffolds.
 Custom synthesis of target compound/processes.
 R &D Process Optimization.
 Collaborative research.
 Intermediate scale (milligram scale to Multi Kilogram Scale).
 Special building block collections in house.
 Skilled at making constrained, complex analogs.
 Skilled at creating new synthetic routes.
 Project Management and Documentation.
Laxmi GenChem

ExpertiseExpertise
 Alkylation, Acylation, Halogenations, Amidation, Condensation, Cyanation, Cyclo-condensation, and
Formylations etc.
 Organo-Metallics- Alkyl Lithium (Metallation – MeLi / n-BuLi / LDA), Grignard reaction, Organoborane
and Silylation reaction etc..
 Palladium Chemistry: Suzuki, Sonogashira, Heck, kumada, Stille, Carbonylation and Buchwald
couplings etc..
 Hydrogenation using Pd/C, Pt/C, Rh/C and Rani-Ni etc..
 Synthesis of Protected N-Terminal & C- Terminal Amino Acids Scaffolds & Di-peptides, Cyclic Peptides.
 Nucleoside chemistry: Modification of Nucleoside bases , Metal Mediating Reactions on Nucleosides,
Modification of Sugar Moieties, Alkylation, Fluorination Reaction at Nucleosides Based and Sugar Moieties etc..
 Asymmetric syntheses, Chiral alkylation, Chiral Amines syntheis, Enantio selective catalysis ,Chiral
auxiliaries and Chiral resolution of racemates etc..
 Wittig Reaction, Mitsunobu Reaction and Vilsmeier-Hack reaction etc..
 Oxidation – Jones, Swern, Dess-Martin Oxidation, KMnO4, NaIO4, OsO4 and K2CrO4 etc.
 Reductions – Catalytic, Metal hydrides, High pressure,Birch reductions, Diborane, LAH, DIBAL-H and
NaCNBH3 etc..
 Beta-Lactam Antibiotices, Macrolides, Steroids and Prostaglandins.
 Special building blocks, API reference standards and Impurity standards.
 Milligram to Kilogram synthesis of complex organic molecules.
 Low to high temperature chemistry.
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Laxmi GenChem

Collaboration ModelsCollaboration Models
 Full time equivalent (FTE)
 Fee for service (FFS) per library
 Single price per compound
Laxmi GenChem

ServiceService
 Contract Research Organization (CRO)
 Medicinal Chemistry/Synthetic Organic Chemistry.
 Library Synthesis/ Parallel Synthetic Chemistry.
 Nucleoside/Sugar Chemistry.
 Amino Acid/ Peptide Chemistry.
 Asymmetric/ Chiral Chemistry.
 Material Chemistry.
 Custom Research & Manufacturing Services (CRAMS)
 API Intermediates and Impurities ( Non-GMP)
9e-mail: vijayreddy@laxmigenchem.com www.LaxmiGenChem.com
Laxmi GenChem

Medicinal Chemistry/Synthetic Organic ChemistryMedicinal Chemistry/Synthetic Organic Chemistry
Laxmi GenChem have extensive experience in synthesizing compounds designed by medicinal
chemists at our clients’ site. Our major focus is given on productivity (milligram to kilogram
scale) and cycle time management in these efforts with real time problem solving in synthesis.
 Medicinal Important compound.
 Biologically active Compounds.
 Metabolites, Antibiotics and Macrolides.
 Steroids and Prostaglandins.
 API reference standards and Impurity standards
After completion of the project all the experimental reports would captured into Word format
(doc or docx) or Structural Database (SD) according Client defined format.
Laxmi GenChem

Library Synthesis/ Parallel Synthetic ChemistryLibrary Synthesis/ Parallel Synthetic Chemistry

Laxmi GenChem have extensive experience in synthesis of a variety of libraries ranging
between focused libraries 10-30 members to large 2000 member libraries, scaffolds/building
blocks including complex structure involving multi-step synthesis in milligram to kilogram
scale with complete characterization, lead generation, lead optimization and SAR libraries
generated in 5-50 mg scale with > 90% purity of LCMS.

After synthesis of the library compounds, Laxmi GenChem would capture all the synthetic
procedure into SAR tables and Structural Database (SD) format in Client defined
format.
Laxmi GenChem

Nucleoside/Sugar ChemistryNucleoside/Sugar Chemistry

 Development of novel methodologies for the synthesis of modified nucleobases and
nucleosides
 Medicinal chemistry of analogues of nucleobases and nucleosides.
 Design and synthesis of novel C-nucleosides for chemical biology.
 Synthesis of modified nucleoside triphosphates
 Novel fluorescent nucleoside labeling for bioanalytical applications.
 Chemical biology of base-modified nucleic acids.
 Click Reaction Applications in Nucelobases.
 Metal Mediating Reactions on Nucleosides (Suzuki, Sonogashira, Heck, Kumada, Stille,
Carbonylation and Buchwald couplings) Modification of Sugar Moieties
Laxmi GenChem

Amino Acid/Peptide ChemistryAmino Acid/Peptide Chemistry
Protected N-Terminal & C- Terminal Amino Acids
 Scaffolds & Di-peptides, Cyclic Peptides.

Asymmetric/ Chiral Chemistry
Chiral alkylation, Chiral Amines syntheis, Enantio selective catalysis,
Chiral auxiliaries and Chiral resolution of racemates.

Material Chemistry/Polymer Chemistry
 Photoactive conducting polymers, charge transporting polymers
 External stimulii small molecules.
 Organic Light-Emitting Diode (OLED) Materials
 Solar Cells: Dye-Sensitized Solar cells and Organic photovoltaic, cells, Conducting
Polymers, Organic Dyes.
Laxmi GenChem

Custom Research & Manufacturing Services (CRAMS)Custom Research & Manufacturing Services (CRAMS)
At Laxmi GenChem ’ facilities, highly skilled chemists routinely carry out syntheses of complex
intermediates and final products With/without technology transfer; starts with process
development/optimization and approval of lab sample, followed by commercial validation campaign,
regulatory filing and approval and then the long-term commercial supply.
 Process Development.
 Route Optimization.
 Manufacturing.
 Validations.
 Impurities – identification, characterization and synthesis.
Laxmi GenChem

API Intermediates and ImpuritiesAPI Intermediates and Impurities
Laxmi GenChem process development chemists are specializing in the design and
optimization of synthetic routes for gram to multi-kilo quantities of compounds suitable
for the transfer of laboratory procedures into the pilot plant. We aim to develop scalable,
safe and economical solutions.
 Route of synthesis- optimization and validation
 Custom research and manufacturing process
 Scale-up & optimization intermediates and related chemicals
 Scale up from lab to pilot and pilot to commercialization (mg level to 1000kg
level)
 Impurity profiling.
Laxmi GenChem

Laxmi GenChem Project Managment

Request for Proposal (RFP) EvaluationRequest for Proposal (RFP) Evaluation
Laxmi GenChem quotes best cost effective pricing model that includes “Synthesis of Target
Compound, Purification and Analysis, Literature Support, Chemical sourcing and shipping
and Project management tools between Laxmi GenChem and the client” or between Laxmi
GenChem and the client’s CRO. Laxmi GenChem CRO scientific team is capable of provides
a best Route of Synthesis (ROS) and alternative of ROS for target compounds based on
literature.
Execution of ProjectExecution of Project
Laxmi GenChem CRO scientific team consists of experienced Ph.D and Master Students,
who have ability to synthesis the target molecule in stipulated timelines. Laxmi GenChem
always keeps 20% buffer back up team for project. Our pioneer Group leader will prepare
weekly reports and arranges a tele-Conference with Client on weekly basis. All the
intermediates and final Compounds are analyzed characterized by NMR and LCMS purity.
After completion of Project, Laxmi GenChem project Management team will provides Final
reports in Word format (Doc & Docx) and Structural data format (SDF & Excel)
documentation in Client defined format.
16
e-mail: vijayreddy@laxmgenchem.com www.Laxmi GenChem.com
Laxmi GenChem

Time LinesTime Lines
Time lines For Quote
Tech Pack is Available : 24- 48 hr
Tech Pack is Not Available : 48- 72 hr
*Based on Chemical Sourcing information time lines may vary.
Time lines For Target CompoundsTime lines For Target Compounds

Laxmi GenChem Chemistry team can deliver target compounds
Single target : 3-4 weeks
Scaffold : 4-6 weeks
Library : 6-8 weeks
*Based on complexcity of compoud time lines may vary.
Laxmi GenChem

Quality PolicyQuality Policy
 Being on time every time to meet our client's needs.
 Consistently meeting or exceeding our client's quality requirements.
 Continuous improvement of our systems and processes.
 Ensuring proper training of our people so as to better serve our clients.
 Recognizing that quality is not just another goal, but a basic strategy for survival and growth.
Laxmi GenChem

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 Quatations for Med.Chem; API & CRAMS
Trackers ( i.e Project; Reagent; Dispatched & SAR).
Final ReportsFinal Reports
Intermediate Inventory
NMR- FID CollectionNMR- FID Collection
Monthly Evaluation tracker
MOM
Project Management- ToolsProject Management- Tools
e-mail: vijayreddy@laxmigenchem.com www.LaxmiGenChem.com
Laxmi GenChem

20
Tracker are historical record for a particular program.
It shows status of all the Ongoing, Holed and Completed
targets status in a structured format.
It is also act as demonstrative tool at Scientific end, BD
end and Client end.
Why Do we need tracker?Why Do we need tracker?
Laxmi GenChem

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What Kind of Information we do find in TRACKER?What Kind of Information we do find in TRACKER?
Laxmi GenChem

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Project Management- Final ReportProject Management- Final Report
Preparation standard Template for Final report. (Preparation standard Template for Final report. ( i. ei. e JOC format)JOC format)
Preparation of finalPreparation of final reports for all dispatched targets.reports for all dispatched targets.
Once compound has been dispatched, time final report has toOnce compound has been dispatched, time final report has to
prepare including Analytical reports with in the 2 weeks.prepare including Analytical reports with in the 2 weeks.
All Final report will be send to Corresponding group leaders for finalAll Final report will be send to Corresponding group leaders for final
proof reading then will be updated in Client e-room.proof reading then will be updated in Client e-room.
Dispatched details in SDF format
Laxmi GenChem

e-mail: vijayreddy@laxmgenchem.com www.Laxmi GenChem.com 23
Intermediate InventoryIntermediate Inventory
 Identify the all key SM and intermediates and Reagents for every finished target.
 Record the information about all key intermediates, key SM and Reagents all
finished target.
 This Process is very much use for Scaffold and Library Synthesis.
Minutes Of Meetings (MOM )Minutes Of Meetings (MOM )
 Organize Tele-Conference with Scientific Team, BD & Client.
Identification of the keys inputs and constraines from Both Sides.
 Record the MOM and updated to Scientific Team, BD & Client.
Laxmi GenChem

Thiazole- Sulfonamide DerivativesThiazole- Sulfonamide Derivatives
BrEtO
O
O
H2N NH2
S
N
S
OEt
O NH2 N
S
OEt
O NH2
Br
N
S
OEt
O
Br
N
S
OEt
O
HO
INT-A
N
S
OEt
O
S N
O
O
F F
Cl
N
S
OH
S N
O
O
F F
Cl
N
S
O
S N
O
O
F F
Cl
Dess-Martin Oxidation
N
SS N
O
O
F F
Cl
EtO
O
wittig Reaction
Mitsunobu
N
SS N
O
O
F F
Cl
EtO
O
N
SS N
O
O
F F
Cl
HO
O
1
2
3 4
5
6 7
8 9
Et-2-Br-Pyruvate
I
O
OAcAcO
OAc
O
INT-A
S
N
H O
O
F
F
ClNH2
FF
S
Cl
O
O
Cl
Py
Bromination
De-Amination Grignard
Reduction Hydrolysis
Diazatization
N
S
NH
S N
O
O
F F
Cl
R
R-NH2/Na(OAc)3BH
DIBAL/THF
NBS/ACN
NaNO2/H2SO4
7
i
PrMgBr/CH3CHO
THF/ -70o
C to - 40o
C
DEAD/TPP/Toulene
Reductive Amination
CH2Cl2
THF
Pd/C/EtOAc LiOH/H2O/THF
H3PO2Heat
N
SS N
O
O
F F
Cl
HN
O
R
EDC/HOBt/DMF
R-NH2
Coupling Reactioin
10
-70o
C to RT
1.LiOH/H2O/THF
2.EDC/HOBt/DMF
N
S
N
H
O
S N
O
O
F F
Cl
R
R-NH2

AA Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3
(JAK2/FLT3) Inhibitor(JAK2/FLT3) Inhibitor
N,O,O-Hetero Macro cyclic compounds
N,N,O-Hetero Macro cyclic compound
N
N
O
N
O
O
N
H
N
N
O
O
N
O
O
N
H
N
N
N
N
H
O

N,O,O-Macro Cyclic Compounds-N,O,O-Macro Cyclic Compounds-Retro SynthesisRetro Synthesis
Disconnection Approach- RCM Route
Disconnection Approach- Non-RCM Route
N
N
O
N
O
O
N
H
1
2
3
4
5
3
6
N
N
O
O
N
O
O
N
H
1
2
4
53
3
6
N
N
O
N
O
O
N
H
1
2
3
4
5
N
N
O
O
N
O
O
N
H
1
2
3 5
6
4

N,O,O-Macro Cyclic CompoundsN,O,O-Macro Cyclic Compounds
N,O,O-Macro Cyclic-RCM Route
28
CHO
OH
O2N
Cl
Cl
CHO
O
O2N
Cl
O
O2N
Cl
HO
Br O
O2N
Cl
O
5-Nitro Salicylaldehyde
O
O2N
N
O
N
H
O
H2N
N
O
N
N
Cl
OH
INT-B
N
N
O
N
O
O
N
H
1 2 3 4
5 6 Target
INT-A
N
N
Cl
Cl
2,4-Dichloropyrimidine
N
N
Cl
B
OHHO
O O
INT-C
N
N
O
N
O
O
N
HMetathesis
Suzuku Rection N
N
Cl
O
INT-C
Br
O-Alkylation
Reduction
N-Alkylation
Reduction
Reduction Bezylic O-Allylation
4N HCl

N,O,O-Macro Cyclic CompoundsN,O,O-Macro Cyclic Compounds
N,O,O-Macro Cyclic-Non-RCM Route
CHO
OH
O2N
Cl
Cl
CHO
O
O2N
Cl O
O2N
Cl
HO
Br
Br O
O2N
Cl
O
Br
N
N
Cl
O
NO2
Cl
O
O
N
H
5-Nitro Salicylaldehyde
pyrrolidine
N
N
O
Cl
O
O
N
H
N
N
Cl
OH
N
N
O
N
O
O
N
H
INT-B
1 2 3
4 5 Target
Reduction O-Allylation
O-Allylation
Coupling Reaction
INT-A
N
N
Cl
Cl
2,4-Dichloropyrimidine N
N
Cl
B
OHHO
O
O
Suzuku Rection Reduction
INT-B
N-Alkylation
Reduction

A Potent Inhibitor of Cyclin Dependant Kinases (CDKs), JanusA Potent Inhibitor of Cyclin Dependant Kinases (CDKs), Janus
Kinase 2 (JAK2) and Fms-LikeTyrosine Kinase-3 (FLT3)Kinase 2 (JAK2) and Fms-LikeTyrosine Kinase-3 (FLT3)
N,N,O- Macro Cyclic RCM Route
30
CHO
O2N
O2N
N
5-Nitro-Benzaldehyde
N
N
Cl
Cl
2,4Dichloropyrimidine
N
N
Cl
B
OHHO
OH OH
N
N
Cl
Br
1 2
O
N
H
H2N
N
3
INT-A
INT-B
N
N
N
N
H
O
N
N
N
N
H
O
INT-B
Metathesis
Suzuku Rection coupling ReactionO-Alkylation
NO2
-
Reduction
Reductive amination

1,2,3,4 tetra hydro quinoline Derivativies1,2,3,4 tetra hydro quinoline Derivativies
N N
H
(Z)
N
(Z)
Quinoline Boc
N
Boc
OH
Br
N
Boc
O
N
Boc
OH
HN
R1
R1NH2
R2X
N
Boc
O
HN
R1
Dry HClR2
N
H
O
HN
R1
R2
N
O
HN
R1
R2
R3 OH
O
R3O
Mitsunobu
Center Inversion
N
Boc
HN
R1
OH R2X
N
Boc
O
HN
R1
Dry HClR2
N
H
O
HN
R1
R2
N
O
HN
R1
R2
R3 OH
O
R3O
Anti
Syn
1 2 3 4
5 6 7
8 9 10
Reduction N-Boc Bromo-Hydrine Epoxidatioin
Opeing of Epoxide O-Alkylation De-Boc Amidation
O-Alkylation De-Boc Amidation

Asymmetric Aldol Products -Chiral Oxazolidinone AuxiliaryAsymmetric Aldol Products -Chiral Oxazolidinone Auxiliary
EXAMPLES
Tetrahedron. 1992, 48, 2132- 2142 J.Org.Chem. 1990, 55, 6260- 6268
32
Chiral
NHO
O
NO
O
1. BuLi
2.n-BuCOCl
O
1. n-Bu2BOTf/ TEA
2.R-CHO
NO
O O
R
OH
HO
O
R
OH
LiOH/ H2O2
THF/ H2O
1
2
TARGET
Aldol Reaction
David A. Evans
(S)-4-benzyloxazolidin-2-one
Evans- SYN
O
B
O
n-Bu
n-Bu
n-Bu
R
H
N
O
O
SYN
HO
O OH
HO
O OH
HO
O OH
HO
O OH
N
HO
O OH
N
Br
Br
Br
HO
O OH
N
HO
O OH
HO
O OH
HO
O OH
HO
O OH
HO
O OH
HO
O OH
HO
O OH

Pyrrolidine Derivativies- Azamethine Ylide
33
N
H
MeO2C
Glycine
Para-HCHO
PhMe/ RefluxBn-Br/ 0 o
C
CO2Me
O
O
O
OBn
O
O
O
2.Pd/C/ EtOAc
1.Boc2O/ TEA DPPA/TEA
BnOH/C6H6 N
Ph
N
MeO2C NHCbz
NPh O
N
Ph
N
NHCbz
1. LiOH/THF
2. SOCl2/Pyrrolidine
O
N
MeOH
Pd(OH)2
N
Ph
N
NH2
O
N
1 2 3
4 5 6
7
TARGET
NaOMe, DMF
O
O
OMe
OBn
I2, xylene
Reflux
Maleic anhydride Azomethine-ylide
Curtius Rearrangement
& Insitu Cbz Protection
N
MeO2C
O
OH
Boc
N
MeO2C NHCbz
Boc
1.De-Boc
Reductive amination
NPh O
Br
HN O
Pd(TPP)4
Buchwald Coupling
De-Bn lation
Cbz- De Protection
Regio Specific addition

Biological Active cyclopetanone-3-amine Derivatives
Bn-Br/ 0 o
C
O
OBn
O
O
O
Pd/C/ EtOAc
2.NaN3/H2O/Bu4NBr
1. LiOH/THF
2. SOCl2/Pyrrolidine
MeOH
Pd(OH)2
1
2
3
4
5
6
NaOMe, DMF
O
O
OMe
OBn
KMnO4/H2O
Curtius Rearrangement
O
O
OMe
OBn
HO2C
HO2C
O
Ac2O/NaOAc
130 o
C/ 5h
O
O
N
H
O
O
O1.(COCl)2/DMF
BnOH
Cbz
O
OH
O
O
O
N
H
O
O
N
Cbz
NH2
O
O
N
O
N3
O
O
O
N
C
O
O
O
O
BnO
Claisen condensation

N
O
N
NH
O
Boc
N
NH
O
Boc
Br
Br
N
NH
O
Boc
N3
N
NH
O
Boc
H2N
N
NH
O
Boc
N
S
O
O
Cl
MeO2C
HN
NH
O
N
S
O
O
Cl
MeO2C
HCl
N
NH
O
Boc
H
N
S
O
O
Cl
NH2OH.HCl/NaHCO3
N
NH
O
Boc
Br
Boc
N
N
Boc
OH
EtOH
PTS-Cl
NaOH/Acetone
Beckmann
Oxime
Br2/PCl5 H2, Pd/C
NaN3/DMF H2, Pd/C
S
O
O
ClCl
TEA/DCM
MeO2C
Br
KOt
Bu/DMF
HCl/ Et2O
1,4-diazepane-Derivativies

Indanone Derivatives
36
R1
CHO
R2
R1
R2
OEt
O R1
R2
OEt
O
O
R1
R2
Cinnamate
OH
R1
R2
R1
R2
R1
R2 O
R1
R2
O
Indane-1-one
Ph3P
OEt
O
Wittig Reaction
H2, Pd/C
EtOH
1.LiOH/THF:H2O
2. SOCl2/CS2/AlCl3
Friedel–Crafts
NaBH4
THF/MeOH
cat. CSA
C6H6/ reflux
mCPBA/DCM
NaHCO3
InCl3/THF
R1 = Cl, Br & F
R2 = H, Cl, Br & F
THF
CHO
OEt
O
OEt
O
O
Cinnamate Indane-1-one
Ph3P
OEt
O
Wittig Reaction
H2, Pd/C
EtOH
1.LiOH/THF:H2O
2. SOCl2/CS2/AlCl3
Friedel–Crafts
R1 = Cl, Br & F
R2 = Cl, Cl & F
THF
R2
R1
R2
R1 R1
R2
R1
R2
R1
R2
R1
R2
O
H2N
O
O
iPrOH/ reflux
S+
I-
NaH HN
O
O
OH
R2
R1
HN
OH
O
OH
LiOH/THF:H2O
Indane-2-one
2,4- Sub
3,5- Sub

Subs of (4-Nitro-1H-imidazol-1-yl)pyrrolidin-2-oneSubs of (4-Nitro-1H-imidazol-1-yl)pyrrolidin-2-one
EXAMPLES
N
O
N
N
O2N
N
O
N
N
O2N
N
O
N
N
O2N
O
N
O
N
N
O2N
OH
N
O
N
N
O2N
N
O
N
N
O2N
N
O
N
N
O2N
N
O
N
N
O2N
Cl
F
F
F
F
Cl
Cl
Cl
J. Med. Chem. 2002, 45, 1184- 1194 J.Org.Chem. 1989, 54, 6069- 6100
37
O O
Br
Br
Br
O
Red P
Br2
RNH2
Br
Br
NHR
O
TEA/THF
NaH/THF
N
R
O
Br
N
N
H
O2N
K2CO3 / DMF N
R
O
N
N
NO2
1 2 3 TARGET
Br
Br
OMe
O
MeOH
K2CO3/Toluene
n-Bu4NHSO4
Br
MeO
O
N
N
H
O2N
K2CO3 / DMF
Et3NBnBr
OMe
O
N
N
NO2

N
N N
Cl
H2N
N
O
R
X N
N N
N
Cl
H2N
R
N
N N
Cl
H2N
R
N
N N
Cl
H2N
R
OH
N
N N
Cl
H2N
R
OH
N
N N
Cl
H2N
N
O
F
N
O
N
N N
N
H2N
Cl
N
N
N
N
N NH2N
Cl
N
O
N
N N
Cl
H2N O
NH
N
N
OH
N
N NH2N
Cl
N
O
OH
Heat Shock Protein-90 Inhibitors
e-mail: vijayreddy@laxmgenchem.com www.Laxmi GenChem.com 38

Heat Shock Protein InhibitorHeat Shock Protein Inhibitor
39
DiBAL-H
SOCl2 scaffold N
N N
OTBDMSCl
O
O
H2N
Br2
Br
DMF
1 2
3 4
N
N N
OHCl
O
O
H2N
Br
TBAF/THF
NaH
5
O
O
O
HO n-BuLi
MeI / THF
6
SOCl2
MeOH THFAcOH
Target
O
O
O
HO O
O
O
O O
O
O
O
Br
O
O
HO
Br
O
O
Cl
BrCHCl3
N
N N
Cl
H2N
PMB
OH
N
N N
H
Cl
H2N
OH
N
N N
Cl
H2N
PMB
OMe
O
N
N N
Cl
H2N
I
PMB
N
N N
H
Cl
H2N
I
1 2 3
TFA / H2SO4
80 0
C/ 2h
Pd(PPh3)4
Binap TEA
100 Psi
L-selectride
K2CO3 / DMF MeOH
PMB-Cl
N
N N
H
Cl
H2N
OTBDMS
TBDMS-Cl
IMD
80 0
C
scaffold
4
Carbonylaation

40
O
O
O
O
HO H+
MeOH
O
AcOH
HNO3 Pd / C
NaNO2
HCl
1
O
O
O NO2
O
O
O
NH2
O
O
O NH
NO2
O
O
O NH2
NO2 Pd/C
EtOAc
O
O
O
NH
NN
O
OH
NH
NN
DiBAL-H
2 3 4
5
6 7 8 9
N
N N
Cl
H2N
O
N
H
N
N
OH
OMe
O
O NH
O
TFA
KNO3
Ac-Cl
Et3N
EtOAc
O
O
O
O
NH2
NH2
Con.-HCl
11
O
Cl
NH
NN
N
N N
H
Cl
H2N
OTBDMS
N
N N
Cl
H2N
O
N
H
N
N
OTBDMS
TBAF
THFNaH
SOCl2
CHCl3
10
Target

41
Pd(dppf)Cl2
bis(pinacolato)diboron
KOAc, dioxane/ 800
C
K2CO3
N
N NH2N
Cl
N
O
F
F
Boc
N
O
H
N
NBoc
N
N NH2N
Cl
N
O
F
F
O
NH
HO HO
TEA DCM / TEA
Boc
N
MsO
K2CO3, DMF
F
F
OHBr
TFA
(Boc)2O Ms-Cl
N
N NH2N
Cl
N
O
I
N
N N
H
H2N
Cl I
K2CO3, DMF
N
O
Br
F F
O
Br
NBoc
F F
O
Br
NH
F F
O
Br
N
AcOH/ CH2O
NaBH(OAc)3TFA
SuzukiINT-A
INT-B
INT-B
N
N NH2N
Cl
N
O
F
F
O
N
Pd(dppf)Cl2
bis(pinacolato)diboron
KOAc, dioxane/ 600
C
K2CO3
F F
O
Br
N
Suzuki
INT-A
N
N NH2N
Cl
N
O
I
N-Methylation
Reductive Aminaation

Biological Active Hetero Cyclic Ring CompoundsBiological Active Hetero Cyclic Ring Compounds
42
N
S
H
N
F3C
O
OEt
5M KOH, MeOH, Reflux N
S
H
N
F3C
O
OH
N
MeO
H.HCl
EDCI/DIPEA/DMF
N
S
H
N
F3C
O
N
OMe
CH3MgBr
N
S
H
N
F3C
O
NH2OH.HCl,
Py, MeOH
N
S
H
N
F3C
H2N
NCS
F3C
NH4OH
Dioxane
H
N
F3C
NH2
S
O
Cl
+
O
H
OEt
N
S
H
N
F3C
N
OH
Zn-AcOH
EtOH/ Reflux
THF/ 0 o
C to RT
weinreb amide
Ketone OximeGrignard Scafold
N
S
H
N
HN
N
N
N
O
O
EDCI / HOBT/ DMF
OH
N
S
H
N
HN
N
N
N
O
HN
O
N
S N
H
K2CO3/ DMF
80 o
C/ 1h.
O
N
N
N
O
1
O
N
S
H
N
HN
N
N
N
O
O
O
6
Br
O
O
O
OH
N
N
N
O
O
O
LiOH
THF/H2O
MeNH2
EDCI / HOBT/ DMF
HCl
F
F
F
F F
F
F F
F
F F
F
NH2
N
N
H
OH
NH2
O
CH2O,HCl
H2O NH
N
N
H
OH
O
SOCl2,MeOH
NH
N
N
H
OMe
O
SeO2,PPSE
N
N
N
H
OMe
O
NEt3, CCl4
Base Hydrolysis
t-Butyl ester is intact
Acid Hydrolysis
2 3
4
7
5
isothiocyanate Thio Urea thiazole
Scafold

Biological Active Hetero Cyclic Ring CompoundsBiological Active Hetero Cyclic Ring Compounds
43
N
NO2
BrBr THF N
O2N
HN Br Fe, AcOH CH(OEt)3, HCl
DMF/H2O
CO, Pd(BINAP)Cl2
Hunig's base, n-BuOH
LiOH
THF/H2O
N
H2N
HN Br
NN
N Br
NN
N CO2Bu
NN
N CO2H
N
S
H
N
CF3
HN
N
N
N
O
1.TFA/DCM
EDCI/HOBT
6
1 2 3 4
5
N
Boc
NH2
N N N N
NN
Boc
Boc Boc Boc Boc
Boc
N
S
H
N
CF3
HN
N
N
N
O
N
2. NaCNBH3
AcOH/CH3CHO
Scafold
Carbonylation
Reductive amination

44
OH
H2N
R1
O
O
H2N
R1
O
(S)-Alanine
O
H
N
R1
O
Boc N
H
H
N
R1
O
NH2
Boc
R2 O
NH
NN
N
H
H
N
R1
R2
Boc
NN
N
H
N
R1
R2
Boc
NN
N
NH2
R1
R2
1 2 3
4 5 TARGET
Esterification N-Boc
Hydrazide
N-Methylation De-BocCyclization
Acid Hydrazide
R1= H, CH3Ph, CH (CH3)2
R2= Me, Ph
R2 O
NH
Dry HCl
MeOHR-CN
Pinner reaction
MeI Dry HCl
4-ME, 3, 5-DI Substitutes- 4H-1, 2, 4-triazols

API Projects

ZudovidineZudovidine
 Chemical Name isChemical Name is 3 -azido-3 -deoxythymidin(AZ′ ′3 -azido-3 -deoxythymidin(AZ′ ′ T).T).
 DNA intercalating drug type.DNA intercalating drug type.
 Retrovir activityRetrovir activity..

StavudineStavudine
 Chemical Name isChemical Name is 2',3'-didehydro-3'-deoxythymidine2',3'-didehydro-3'-deoxythymidine.BRAND Name is.BRAND Name is ZeritZerit
 StavudineStavudine is converted within the body to its activeis converted within the body to its active formform ((stavudinestavudine
triphosphatetriphosphate). This active form is similar to). This active form is similar to thymidine triphosphatethymidine triphosphate, a chemical, a chemical
that is required by the HIV virus to make new DNA.that is required by the HIV virus to make new DNA.

48
Capiceitabine (Anti-Tumor drug/ Xeloda Trade Name)

49
Lacosamide (Anticonvulsant / Vimpat Trade Name)

50
Montelukast Na (leukotriene receptor antagonist /
Singulair Trade Name)

Vardenafil-INT
Vardenafil is a PDE5 inhibitor used for treating erectile dysfunctionVardenafil is a PDE5 inhibitor used for treating erectile dysfunction

Trans-4-Amino-1-cyclohexanecarboxylic Acid HClTrans-4-Amino-1-cyclohexanecarboxylic Acid HCl

Methyl trans-3-amino-cyclobutane HCl

(Toluene-4-sulfonylmethyl)-phosphonic acid diethyl ester

1,1-difluoroethanesulfinate (Hu'S Reagent) Derivatives

Perampanel –INT (1-Phenyl-5-(pyridin-2-yl)-2(1H)-pyridone)

Saxitoxin-Natural Product. ( Total 19 Steps)

Sofosbuvir Synthesis

Sofosbuvir Alternative ROS

PL- 102 ( IsoSteric Structure to Sofosbuvir)

Ledipasvir-IMP-4 Synthesis ( Total 24 Steps)

ADU-S100 Synthesis ( Total 21 Steps)

Medicinal ChemistryVijay M Reddy 65
Synthesis of G007-LK-Tankyrase 1/2 Inhibitor
Ref: J. Med. Chem. 2013, 56, 3012−3023

Research Work

N
N
N
N
O
O
O
O
R
R
R
R
α- PolyPeptide chaine
N N N
O O O
RRR
H
H
H
H
H HH
α
β2
- PolyPeptide chaine
β
α α
α
β β
N N N
O O O
H HH
β3
- PolyPeptide chaine
β β β
R R R
Types of Amino Acid & Poly peptideTypes of Amino Acid & Poly peptide
Vijay M Reddy Medicinal Chemistry 67

Peptide-based nano structuresPeptide-based nano structures
68Vijay M Reddy Medicinal Chemistry

Choice of Backbone Structure
1972 Hassel predicted that cyclic tetra peptides composed by alternative α and β- amino acids
would stack through backbone- backbone H-bonding to form hollow cylindrical structure.
Later X-ray crystallographic work partially validated these prediction. Two of four expected
inter subunit H-bonding was observed.
1974 De Santis and co workers recognized the possibility of forming cylindrical structure by
ring –stacking of cyclic D,L- α- peptides.
 Early attempts to experimentally verify this prediction met with limited success due to the
extreme insolubility of peptides examined.
1993 Ghadiri and co workers complied 1st
evidence of forming hollow tubular structure by self
-assembly of cyclic D,L- α- peptides, by bearing suitable hydrophobic side chain.
 Molecular modeling and experimental studies indicated that 8 –residue cyclic peptides possess
optimum balance of low ring-strain .
Ghadiri, M. R et al. Nature 1994, 369,301- 304.
Ghadiri, M. R et al. J. Am. Chem. Soc. 1998, 120, 651- 656.
Ghadiri, M. R et al. J. Am. Chem. Soc. 1996, 118, 43-50.

Choice of Backbone Structure
Cyclic D,L- α- peptides with 8, 10 and 12-residue which give internal Van der waals diameters
7, 10, 13 Å respectively.
1996 Dieter Seebach reported that cyclic tetramers of β3
- amino acids can adopt flat ring
confirmation and stack in the solid state through back- back bone H-bonding.
Seebach, et al. HelV. Chim. Acta 1997, 80, 173-182
(a) flat-ring C2 symmetrical conformation
described by Seebach
(b) an alternative flat-ring C4 symmetrical conformation.
central hole 2.6-2.7Å in diameter, large enough to allow
passage of water and small ions

A ModelA Model CycloCyclo Peptide Nano tubesPeptide Nano tubes
In β3
-Tetra peptides CH2- Group α to
Carbonyl group is responsible for optimum
balance of Cyclo Peptides.

Structural attribute of Cyclic Peptide
NoNetDipoleMoment
α - Octa Peptide Nano tube
N
N
N
N
N
N
O
OO
O
O
O
R
H H
HH
H
H
N
O
N
O
R
H
H
N
N
N
N
N
N
O
OO
O
O
O
R
H H
HH
H
H
N
O
N
O
R
H
H
N
N
N
N
N
N
O
OO
O
O
O
R
H H
HH
H
H
N
O
N
O
R
H
H
N
N
N
N
N
N
O
OO
O
O
O
R
H H
HH
H
H
N
O
N
O
R
H
H

Ghadiri’s α-cyclic polypeptides

Some other cyclic polypeptide

Jan H. van Maarseveen et al.Org. Lett., Vol. 8, No. 5, 2006, 919-922
Tyrosinase inhibitor- Click Chemistry Approach
Cyclo- [Pro-Val-Pro-Tyr] is a natural product isolated from Lactobacillus helveticus.
Tyrosinase (phenol oxidase) [EC 1.14.18.11 is known to be a key enzyme for melanin
biosynthesis in plants, microorganisms and mammalian cells, and also known to be as a
copper-containing enzyme.
Compound Tyrosinase activity
IC50/mMa
cyclo-[Pro-Tyr-Pro-Val] 1.5
Triazole analogue 2 0.5
(S) N
(S)
O
NH
N
(S)
HO
(S)
HN
O
O
O
Cyclo- [Pro-Val-Pro-Tyr]
Pro
Pro Val
Tyr

Reasons behind the Replacement of PeptideReasons behind the Replacement of Peptide
Bond with Hetero CyclicBond with Hetero Cyclic
 Triazole & Oxadiazoles mimics planarity of amide bond.Triazole & Oxadiazoles mimics planarity of amide bond.
 Triazole and peptide bond both possess large dipole (5D, 3.7D, respectively).Triazole and peptide bond both possess large dipole (5D, 3.7D, respectively).
 CCαα distancedistance ofof Peptide and TriazolePeptide and Triazole && Cβ distanceCβ distance ofof triazole and oxadiazoletriazole and oxadiazole areare comparable.comparable.
 Peptide bond Hetero cyclic arePeptide bond Hetero cyclic are Isoteric Structures.Isoteric Structures.
Jan H. van Maarseveen et al.Org. Lett., Vol. 8, No. 5, 2006, 919-922
Kolb, H.C., Sharpless, B.K. Drug. Disc. Today. 2003, 8, 1128-1136.
Kevin Burges, J. AM. CHEM. SOC. 2011, 133, 462–477

N N
O(S)
NH
(S)
R2HN
O
NN
O (S)
HN
(S)
R2 NH
O
R1
R1
N
N
O
(S)
HN
R1
(S)
R2
HN
O
N
N
O
(S)
N
H
R1
(S)
R2 HN
O N
N
O
(S)
NH
R1
(S)
R2
NH
O
N
N
O
(S)
H
N
R1
(S)
R2
NH
O
H
H
H
H
H
H
H
H
C2
C4
CC22 & C& C44 Symmetry 1,3,4- Oxadiazole Back Bone Cyclic PeptidesSymmetry 1,3,4- Oxadiazole Back Bone Cyclic Peptides
Monomer consist of 2-Amino acids with 1,3,4-Oxadiazole

Chemistry Scheme Execution
OH
O
H2N
R1
O
O
H2N
R1
O
OH
N
R1
Boc N
H
OH
N
R1
Boc
NH2
SOCl2/MeOH
reflux; 6h;
(Boc)2O/TEA
DCM, RT
Over night
Hyrazinehydrate
MeOH/ Reflux
4h
OH
O
Cl
N N
N
N
O
N N
O
Cl
N
H
OH
N
Boc
NH2
N
H
OH
N
R1
Boc
H
N
Cl
ODCM/ RT/ 6hDCM ACN/ Reflux/ 4h
PTS-Cl/ TEA N N
OR1
NH
Boc
Cl
R1= CH3, Ph, Leu & Val
N N
OR1
NH
Boc
I
R2
H2N
O
O
N N
OR1
NH
R2
HN
O
OO
O TFA/DCM
N N
OR1
NH2. TFA
R2
HN
O
OTEA /ACN
KI/Acetone
Finkelstein reaction A B
R2= Leu, Cys, Trp, Typ & His

Future Chemistry Scheme Execution
N N
O
NH
R1 R2
HN
O
O
NN
O HN
R1
R2 NH
O
Boc
Dimarization
A X B
N N
O
NH HN
O
NN
O
HNNH
O
R1
R1
1) TFA/DCM
2) Coupling
N N
O
NH
R1 R2
HN
O
NN
O NH
R1
R2 NH
O
NN
O
HN
R1
R2
NH
O
O
N N
O
N
H
R1
R2HN
O
Boc
N
N
O
HN
R1
R2
HN
O
N
N
O
N
HR1
R2 HN
O N
N
O
NH
R1
R2
NH
O
N
N
O
H
N
R1
R2
NH
O
H
H
H
H
H
H
H
H
Coupling
1) TFA/DCM
2) Coupling
1) TFA/DCM
2) Coupling

Application of SA peptidesApplication of SA peptides
 New Materials
 Sensors
 Molecular electronics
 Ions Channels
 Antimicrobial

Location
Our R&D Centre is located at Hyderabad in South India - a vibrant city that pharma-
hub of India and home to several global IT and biotech companies, pharmaceutical and
related industries.
R&D Address
PLOT NO-90,ALEAP INDUSTRIAL ESTATE,
OPP- KPHB, PRAGATHI NAGAR,
HYDERABAD-500090,AP,INDIA.
WEB: www.laxmigenchem.com
Laxmi GenChem

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