Research Chemistry

CURRICULUM VITAE

Yesu Addepalli

OBJECTIVE

Wish to pursue a post-doctoral research career in synthetic organic chemistry with a special emphasis on Organo Catalysis, Medicinal Chemistry and Chemical Biology to address the contemporary challenges.

PERSONAL DETAILS

Date of Birth: June 01, 1991; Sex: Male

Marital Status: Unmarried; Nationality: Indian

ACADEMIC QUALIFICATIONS

Ph.D (Organic Chemistry)

2014 Sept – July 2018

Supervisor: Prof. Dr. Yun He

Innovative Drug Research Centre, Huxi Campus, Chongqing University, Shapingba, Chongqing, P.R. China

Research Work

(i) Development of aryne mediated synthetic methodologies for Synthesis of (a) Polycyclic indole derivatives

(b) Benzo[c]xanthone derivatives

(ii) Design, synthesis and anticancer activity studies of the

(a) Azacalix[2]arene[2]pyrimidines derivatives

(b) N-sulfonyl-1H-1,2,4-triazol derivatives

(iii) Total Syntheses of cyclic depsipeptide ilamycins B1 Present Address:

C/o Prof. Dr. Yun He

School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University, H uxi Campus, No. 55, Daxuecheng south Rd.,

Shapingba District,

Chongqing city, China - 401331.

Mobile No: +86-130********

.

Mail ID: *************@*****.***

2011 – 2013 Master of Science (M.Sc.), Organic Chemistry (first division), Andhra University, Visakhapatnam, India.

2008 – 2011 Bachelor of Science (Chemistry, Physics, Mathematics) (first division), Andhra University, Visakhapatnam, India. INDUSTRIAL EXPERIENCE

Worked at GVK Biosciences Private Limited, Hyderabad, India From (August 2013 – August 2014) as Research Chemist. Research work on Neuroscience and drug discovery and library synthesis.

AWARDS AND FELLOWSHIPS

Selected for prestigious Chinese Government Scholarship conducted by Chinese Scholarship Council (CSC)-2014, China.

Certificate of Academic Honor Society in Chemistry in M.Sc. (Organic Chemistry) – First division with Distinction.

Certificate of Academic Honor Society in Chemistry in B.Sc. (Chemistry) – First division. EXPERIENCE AND SKILLS

Methodologies: Development of new reactions and methodologies for the efficient synthesis of biologically active molecules

Medicinal Chemistry: Lead generation/optimization, Structure-based drug design and Synthesis of organic molecules for biological, medicinal and material science applications.

Natural product synthesis: Synthesized biologically active of Cyclic Peptide Natural Products

Multi-step Organic Syntheses: Many unnatural chiral and achiral compounds were designed and synthesized in milligram to pilot plant scale.

Skilled in handling and interpretation of spectroscopic data of NMR, IR, Polarimeter, HRMS, LC-MS, HPLC, GC-MS, IR towards the characterization of unknown organic compounds.

Responsible for Scientific reports generation and Lab note book monitoring on daily basis.

Literature search through reaxys and Scifinder to solve the chemistry related problems RESEARCH INTERESTS

Medicinal Chemistry and Chemical biology.

Development of newer methodologies for the biologically active scaffolds.

Development of parallel synthesis to provide compound libraries to explore SAR.

Total synthesis of natural products.

LIST OF PUBLICATIONS

1. Zhen Wang,* Yesu Addepalli, Yun He,* Construction of Polycyclic Indole Derivatives via Multiple Aryne Reactions with Azaheptafulvenes, Org. Lett. 2018, 20, 644 647. DOI: 10.1021/acs.orglett.7b03789.

2. Yesu Addepalli, Xiaohong Yang, Minghui Zhou, D. Prabhakar Reddy, Shao-Lin Zhang, Zhen Wang,* and Yun He,* Synthesis and anticancer activity evaluation of novel azacalix[2]arene[2]pyrimidines, Eur. J. Med. Chem. 2018, 151, 214–225. DOI: 10.1016/j.ejmech. 2018.02.079.

3. Yesu Addepalli, Zhimei Yu, Jie Ji, Cheng Zou, Zhen Wang,* and Yun He,* Tandem Diels Alder/Oxidation Aromatization Reaction of 2-Styrylchromones with Arynes: Synthesis of Benzo[c]xanthones, Org. Biomol. Chem. 2018 (Under review) 4. Yesu Addepalli, Xiaohong Yang, Yun He,* Design, synthesis and antiproliferative activity of novel N-sulfonyl aryl-1,2,4-triazole derivitives, Eur. J. Med. Chem. (Manuscript under preparation) 5. Minghui Zhou, Qin Su, Yesu Addepalli, Yun He,* and Zhen Wang*Asymmetric Mannich reaction of α-Diazocarbonyl compounds and N-sulfonyl Cyclic Ketimines Catalyzed by Complexes Generated from Chiral and Achiral Phosphines with Gold(I), Org. Biomol. Chem. 2018, 16, 2923– 2931. DOI: 10.1039/C8OB00577J.

6. Yesu Addepalli, Zhimei Yu, Yun He,* Total Syntheses of cyclic depsipeptide ilamycins B1 (in progress).

DOCTORAL RESEARCH SUMMARY

1. Construction of Polycyclic Indole Derivatives via Multiple Aryne Reactions with Azaheptafulvenes

(Org. Lett. 2018, 20, 644 647.)

An efficient [8+2]/aryl ene tandem reaction between azaheptafulvenes and arynes has been developed, leading to the formation of cyclohepta[b]indoles in a single step with good yield. In addition, employment of excess arynes provides a [8+2]/aryl ene /[6+2] tandem reaction to synthesize polycyclic oxacyclohepta[b]indoles. This is the first time that azaheptafulvenes have been employed in tandem reactions with arynes.

2. Synthesis and anticancer activity evaluation of novel azacalix[2] arene[2] pyrimidines

(Eur. J. Med. Chem. 2018, 151, 214–225.)

A series of novel azacalix[2]arene[2]pyrimidines were synthesized, and evaluated for their antiproliferative activities against A549, MCF7, SH-SY5Y and CNE human cancer cell lines in vitro by using the CCK-8 assay. A number of compounds showed low micromolar antiproliferative activities against MCF7 cell line. Compound 4j, containing a pyrrolidine moiety, exhibited the strongest inhibitory activity with an IC50 value of 0.58 μM. Furthermore, breast cancer cells were used to explore the inhibition mechanism of these azacalix[2]arene[2]pyrimidines. The results suggested these compounds were involved in inducing cell apoptosis via up-regulation of caspase-3 and caspase-9 protein expression, and the cell cycle was arrested at the S phase. Our reports here represent the first studies on the biological activities of azacalix[2]arene[2]pyrimidines. 3. Tandem Diels Alder/Oxidation Aromatization Reaction of 2-Styrylchromones with Arynes: Construction of Benzo[c]xanthones

Org. Biomol. Chem. 2018 ( Under review)

Transition-metal-free Diels-Alder and tandem Diels Alder/oxidation aromatization reaction of 2- styrylchromones with arynes have been demonstrated under mild reaction conditions with a wide range of substrates. This efficient protocol allows rapid access to both dihydro benzo[c]xanthone and benzo[c]xanthone derivatives selectively by simply changing the atmosphere of the reaction. 4. Design, synthesis and antiproliferative activity of novel N-sulfonyl aryl-1,2,4- triazole derivitives

Eur. J. Med. Chem. (Manuscript under preparation)

A series of novel N-sulfonyl aryl-1,2,4-triazole derivitives were designed, synthesized and evaluated for their antiproliferative activity against five selected cancer cell lines (against A549, MCF7, U266, MM1S and MV4-11). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. The N-sulfonyl aryl-1,2,4-triazole derivatives 18b and 18e were the most active compounds against MM1S and MV4-11 cells, respectively Particularly, compound 18a showed the most excellent antiproliferative activity with an IC50 value of 0.19 μM against MV4- 11cancer cells. Moreover, SAR conclusion based on study clearly identified a structural feature that should be retained for good activity and also a moiety that can tolerate various modifications and may find potential medicinal applications with further structural modulations and biological studies. 5. Asymmetric Mannich reaction of α-Diazocarbonyl compounds and N-sulfonyl Cyclic Ketimines Catalyzed by Complexes Generated from Chiral and Achiral Phosphines with Gold(I)

(Org. Biomol. Chem. 2018, 16, 2923–2931.)

An unprecedented Lewis acidic gold(I)-complex generated from chiral and achiral phosphines has been developed for the Mannich reaction of α-diazocarbonyl compounds and N-sulfonyl cyclic ketimines. A series of chiral β-amino-α-diazoesters bearing a quaternary stereocenter were obtained in high yields with good enantioselectivities. In addition, the products could be converted to promising bioactive spirosuccinimide. Furthermore, Operando IR, NMR and control experiments were carried out to gain insight into the mechanism.

7. Total Syntheses of cyclic depsipeptide ilamycins B1

(in progress)

The first total synthesis of the potent antimycobacterial cyclic depsipeptide natural product ilamycin B1 is described. Key features of our synthesis include the concise preparation of a linear cyclization precursor that consists of only L-amino acid residues (L-N-methyl leucine, L-tryptophan derivative, L-2-amino-tran&hexenoic acid, L- leucine, LN-methyl leucine, L-alanine and L-3-nitrotyrosine) and its macrolactamization from a bent conformation.The cyclic core of the ilamycins was shown to be responsible for the excellent antituberculosis activity

REFERENCES

1. Prof. Dr. Yun He (supervisor) 2. Dr. Wang Zhen

Dean-School of Pharmaceutical Sciences. Associate professor Director-Innovative Drug Research Centre. School of Pharmaceutical Sciences & Innovative Huxi Campus, Chongqing University. Drug Research Centre. No.55 Daxuecheng South Rd. Chongqing University.

Shapingba, Chongqing, P.R.China Chongqing,P.R.China. http://www.iddts.com E-mail: *********@***.***.**

Fax: +86-23-656*****

E-mail: ***.**@***.***.**

3. Dr. Jian Guo

Associate Professor

School of Pharmaceutical Sciences & Innovative

Drug Research Centre.

Chongqing University.

Chongqing, P.R. China.

E-mail: ***********@***.***

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