Curriculum Vitae Venkatachalam Angamuthu

*

Venkatachalam Angamuthu, Ph. D

Dr. Venkatachalam, Ph. D

Post-doctoral research fellow

Center for supramolecular chemistry and catalysis

Shanghai university

99 Shang Da Road,

Baoshan District,

Shanghai,

China: Zip code: 200444

Mobile No: +91-637*******

Email: ac95c1@r.postjobfree.com

Profile

Fifteen years of cumulative research experience in organic chemistry, organometallics and medicinal Chemistry.

Highly proficient in diverse areas of organic synthesis including synthetic methods, asymmetric catalysis, catalytic reactions and combinatorial approaches.

Strong experience in proposing state of the art research, developing standard operating procedures, design and performing experiments, analyze the results and publishing peer-reviewed journal papers Educational qualifications

Post-doctoral researcher at Shanghai University, Shanghai [2017-present]-Supramolecular chemistry, Prof. Julius Rebek Jr group.

Post-doctoral researcher at National Central University, Taiwan [2015-2017]-Total synthesis and methodology, Prof. Duen-Ren Hou research group.

Ph.D. in Synthetic organic chemistry [2009-2015], Department of chemistry, National Dong Hwa University, Hualien, Taiwan.

Title of the Thesis: Total synthesis of -antrocin and proline based chiral amine

M. Sc. in Chemistry [2003-2005], Department of Chemistry, Bishop Heber College, Bharathidasan University, Tiruchirappalli, India.

Title of the project: Binding of organic azo dyes to nucleic acids. Elective: Organic, physical, Inorganic and Analytical chemistry.

B. Sc. in Chemistry [2000-2003], Bishop Heber College, Bharathidasan University, Tiruchirappalli, India.

Ancillaries: Physics and Mathematics.

Ph.D. thesis

Thesis Title: Total synthesis of -antrocin and proline based chiral amine Supervisor: Prof. Dar-Fu Tai

Research experience

Curriculum Vitae Venkatachalam Angamuthu

2

Shanghai University, Shanghai, China: Post-doctoral research fellow [Aug-2017-present].

National Central University, Zhongli, Taiwan (ROC): Postdoctoral research fellow [Nov-2015 to Aug-2017].

Hikal Ltd, R&D centre, Banglore: Worked as a research officer [Mar-2006 to Sep-2009]. Synthesized many organic intermediate & final drugs (Verapamil hydrochloride, Ondansetron hydrochloride, Triticonazole, Naltrexone & Quetiapine) with efficient methods.

Leonid Chemical Pvt. Ltd., Bangalore: Worked as a research officer [Jul-2005 to Mar-2006]. Synthesized protected amino acid and peptides and bioactive intermediates. Research and instrumental skills

Self-motivated, independent researcher with good interpersonal and communication skills. Extensive experience in the synthesis of complex organic molecules, amino acids and peptide based moisture and acid sensitive compounds.

Synthesis and characterization of complex organic molecules and developing new methodologies.

Capable of executing multi-step synthesis and familiarity with all the chromatographic purification techniques used to separate the reaction products.

Experienced in handling the air/moisture sensitive reagents, solvents, and in metal catalysis reaction.

Familiar in planning of synthetic methods to obtain target molecules.

Capable of handling small scale as well as large scale organic reactions.

Analytical techniques: Characterization of molecules by (Proficient with operation and interpretation) using of UV, IR, 1H & 13C-NMR, 2D-NMR (COSY and NOESY). Semi-preparative HPLC (Shimadzu LC-8A model).

LC-MS, HRMS, IR, UV, HPLC, GC.

Computer Awareness: Word Processor: MS Word, MS Excel, and Power Point.

Other Software: Elsevier MDL Crossfire Data search, Discovery gate, Scifinder Scholar, Reaxys, ISIS Draw, Chem draw Ultra 7.0, 10.0, 12.0 and 13.0 version (Cambridge soft), ACD Lab Demo. Research interests

Total synthesis of natural products.

Synthesis of valuable organic intermediates, fine chemicals and biologically active compounds.

Recyclable magnetically immobilized organic ligands nanoparticle and its applications towards asymmetric synthesis of organic bioactive molecules.

Research publications

1. Venkatachalam Angamuthu, Manuel Petroselli, Faiz-Ur Rahman, Yang Yu* and Julius Jr. Rebek*, Binding orientation and reactivity of alkyl α,ω-dibromides in water-soluble cavitands, Org. Biomol. Chem. 2019, 17, 5279-5282. 2. Venkatachalam Angamuthu, Dar-Fu Tai*, New chiral morpholine-pyrrolidine ligands affecting asymmetric selectivity in copper catalyzed henry reaction, Tetrahedron Lett., 2019, 60, 653-659. 3. Venkatachalam Angamuthu, M. Shanmugavadivu, G. Nagarajan, Bharath Kumar Velmurugan*, Pharmacological activities of antroquinonol- Mini review, Chem. Biol. Interact. 2018, 29, 8-15 Curriculum Vitae Venkatachalam Angamuthu

3

4. Venkatachalam, Angamuthu, Wen-Jung, Chang and Duen-Ren, Hou*, Anti-addition of dimethylsulfoxonium methylide to acyclic α,β-unsaturated ketones and its application in formal synthesis of an eicosanoid, ACS Omega, 2017, 2, 4088–4099.

5. Venkatachalam Angamuthu, Long-Shiang Li, and Duen-Ren Hou*, Palladium catalyzed allylic substitution for the synthesis of pericosines, Asian J. Org. Chem., 2016, 5, 1327-1333. 6. Dar-Fu Tai*, Venkatachalam Angamuthu, Yew-min, Tzeng, Processes for preparing optically active antrocin, Patent, US8658806 B2, Feb 25/2014.

7. Venkatachalam Angamuthu, Dar-Fu Tai*, Asymmetric reactions of chiral organo-magnetic nanoparticles, Appl. Catal A. Gen., 2015, 506, 254-260.

8. Venkatachalam Angamuthu, Dar-Fu, Tai*, Chiral amine and macrocycle fabricated magnetic nanoparticle asymmetrically catalyzed direct aldol, Sus. Chem. Phar., 2019, 13, (Article no: 100152).

(https://doi.org/10.1016/j.scp.2019.100152).

9. Venkatachalam Angamuthum, Manuel Petroselli, Faiz-Ur Rahman, Yang Yu* and Julius Jr. Rebek*, Mono epoxidation of α,ω-dienes using NBS in a water-soluble cavitand, Org. chem. Front., 2019, DOI: 10.1039/C9QO00849G. 10. Venkatachalam Angamuthu and Dar-Fu Tai.* Brucine diol and brucine-N-oxide fabricated MNPs catalyzed asymmetric Morita–Baylis–Hillman reaction, Molecular catalysis. Under review. 11. k. Sampath1,*, R. Ashok kumar, V. Angamuthu and m. Shanmuga Prakash, Synthesis, characterization and cytotoxic antibacterial activity of Ru(II) ethoxysalal thiosemicarbazone complexes, Rasayan J. Chem., 2019, 12, 257- 261.

International and National Conferences

13th Tetrahedron Symposium, Taipei (Taiwan). Nov-2012, Poster presentation. Topic: Total synthesis of -antrocin.

National symposium on recent trends in Biotechnology, Bishop Heber College–Tiruchirappalli (TN, India). Mar-2005, Topic: Binding of some organic azo-dyes to nucleic acids.

Horizan’3 (A national level symposium), NIT, Tiruchirappalli (TN, India). Jun-2004. Poster presentation. Topic: Inorganic metal pollutions.

Personal information

Father : M. Angamuthu

Mother : A. Anjalam

Nationality : Indian

Languages Known : English, Tamil, Kannada and Telugu Marital Status : Married

Date of Birth : 04.03.1983

Permanent Address : 2/61, Enam pudur (Village),

Mathagri (Post),

Manapparai (Taluk)

Trichy (Dist), Tamil Nadu (State)

India.

Pin: 621313

E.Mails : ac95c1@r.postjobfree.com

ac95c1@r.postjobfree.com

Curriculum Vitae Venkatachalam Angamuthu

4

Mobile Number : +86-131******** (Shanghai, China) References

Prof. Dar-Fu Tai, Ph. D

Department of Chemistry,

National Dong Hwa University,

Hualien, Taiwan (R.O.C).

Tel.: +886-*-***-****; Fax: +886-*-***-****

E-mail: ac95c1@r.postjobfree.com

Prof. Duen-ren Hou,

Department of chemistry,

National central university,

No. 300, zhongda Rd.,

Zhongli District, Taoyuan city 32001, Taiwan (R.O.C) E-mail: ac95c1@r.postjobfree.com

Prof. Julius Rebek Jr

The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

E-mail: ac95c1@r.postjobfree.com

Research Summary

Summary of the Ph. D Thesis

My thesis research has been mainly focused on the total synthesis of -antrocin natural product and its enantiomer. Another topic was synthesis of proline based chiral amine ligands and its application toward the asymmetric Henry reaction was studied.

In first section, an attempt have made for synthesis of -antrocin via intramolecular Diels-Alder reaction. So we developed acetonide, sillyl, di, tri-acetyl protected trienolides such as 13, 14, 15 and 16 (Diels-Alder precursors) having appropriate diene dienophile tethered chiral functionality for the synthesis of trans-fused tricyclic core ring (ABC) structural framework. The generalized synthetic sequences depicted in Scheme 1. After synthesis of those trienolides, a number of methods have been tried, in order to synthesize Diels-Alder adduct using thermal as well as Lewis acid mediated reaction conditions; but unfortunately, the planned intermolecular Diels-Alder (IMDA) cycloaddition reaction was unsuccessful. Curriculum Vitae Venkatachalam Angamuthu

5

Scheme 1. Trienolides synthesis for IMDA reaction

In second section, the total synthesis of -antrocin 1 was completed using an alternative synthetic route as shown in scheme 2 and scheme 3. A tricyclic core ring structure was successfully accomplished by kinetic controlled regioselective aldol reaction of bicyclic keto aldehyde -28 using ethereal solution of formaldehyde. Alkylation of 3-methyl-2-cyclohexenone 17 with iodoethyl- 2-methyl-1,3-dioxolane 18 followed by 1,4-addition with CuI/MeLi in diethyl ether solution to obtained 3,3- dimethylcyclohexanone 20. The formation of bicyclic ketone 23 under aldol reaction and further stereo selective trans-HCN addition reaction of unsaturated bicyclic ketone furnishing the cyano bicyclic ketone trans -23 (scheme 2). Curriculum Vitae Venkatachalam Angamuthu

6

Scheme 2. Synthesis of trans -23

As shown in Scheme 3, the development ketal -24, as a starting material has paved the way for efficient and elegant protocol to prepare tricyclic core ring structure -29 by the following reaction sequences: (1) deprotection followed by ethylene glycol protection, (2) DIBALH Reduction, (3) acid hydrolysis with glacial acetic acid/water mixture (4:1), (4) regioselective α- hydroxylmethylation using kinetically controlled conditions at –78 C with ethereal saturated solution of gaseous formaldehyde. Scheme 3. Complete synthesis of -antricin

Curriculum Vitae Venkatachalam Angamuthu

7

The exclusive formation of the expected tricyclic Hemi acetal -29 was confirmed by the shift in the methylene (CH) carbon in the 13C, DEPT and NOESY spectra shows secondary hydroxyl function. Oxidized by silica supported PCC, which gave lactone - 30 exclusively. The structure of -30 was confirmed by X-ray crystallographic method. Finally, the reaction with non-basic Lombardo’s reagent (Zn, TiCl4, CH2Br2) led to smooth olefination of lactone -29 to -antrocin 1 in excellent yield (98%). In third section, we developed 13 different novel proline based chiral amines and amino alcohol such as 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, and 43.

Applications in copper catalyzed Henry reaction of these amine ligands have also been studied. During the examination of these ligands, the ligand 31 found to have good catalytic activity towards asymmetric Henry reaction and it was provide Henry adduct 45 in 89% of yield and 65% of enantiomeric excess.

Scheme 4. Asymmetric Henry reaction

Industrial Research project summary at Hikal Ltd.

Project 1: I developed a non-infringing process for the preparation of Quitiapine hemi-fumarate to good yield and purity starting from aminodiphenyl sulphide.

Curriculum Vitae Venkatachalam Angamuthu

8

Scheme 5. Synthesis of Quetiapine hemi-fumarate

Project 2: Synthesis of MOA-728 from Morphine:

The synthesis of N-methylnaltrexone bromide (MOA-728) was successfully carried out from the reaction of morphine with shortest reaction sequencies. This route enables the gram scale synthesis of MOA-728 (over all yield = 16.12) (Scheme 5). Scheme 6. Synthesis of MOA-728

Project 3: In order to improve the yield and purity of the drug verappamil HCl, we developed simple protocol whereby we could synthesis substantial quantity of verappamil HCl with good overall yield and purity. Curriculum Vitae Venkatachalam Angamuthu

9

Project 4: Novel synthetic strategy for synthesizing triticonazole intermediate starting from cyclopentanone was developed. This route provides an efficient method to synthesis in gram scale without much operational workup and economically low cost process.

(Scheme 7).

Scheme 7. Synthesis of Triticonazole intermediate

Contact this candidate