Large scale synthesis of chiral (3Z,5Z)-2,7-dihydro-1H-azepine-derived Hamari ligand for general asymmetric synthesis of tailor-made amino acids.

 

(R)-2,2′-bis(bromomethyl)-1,1′-binaphthalene ((R)-17) was prepared in the identical manner and had identical analytical properties to those given here.

¹H NMR (400 MHz, CDCl₃): δ 4.25 (4H, s, 2 × CH₂), 7.07 (2H, dd, J = 8.4, 0.8 Hz, ArH), 7.27 (2H, ddd, J = 8.4, 6.8, 1.2 Hz, ArH), 7.48 (2H, ddd, J = 8.2, 6.8, 1.2 Hz, ArH), 7.74 (2H, d, J = 8.6 Hz, ArH), 7.92 (2H, d, J = 8.2 Hz, ArH), 8.02 (2H, d, J = 8.6 Hz, ArH).

¹³C NMR (100.6 MHz, CDCl₃): δ 32.6 (CH₂), 126.80 (ArCH), 126.82 (ArCH), 126.84 (ArCH), 127.7 (ArCH), 128.0 (ArCH), 129.4 (ArCH), 132.5 (quaternary ArC), 133.3 (quaternary ArC), 134.1 (quaternary ArC), 134.2 (quaternary ArC).

[α]²⁰_D = +173.8° (c = 1.0, CHCl₃).

An advanced process for large scale (500 g) preparation of a (3Z,5Z)-2,7-dihydro-1H-azepine-derived chiral tridentate ligand (Hamari ligand), widely used for asymmetric synthesis of tailor-made α-amino acids via the corresponding glycine Schiff base Ni(II) complex, is disclosed. The process includes amidation, bis-alkylation, and precipitation/purification of the target compound by TFA as a counterion.

Large Scale Synthesis of Chiral (3Z,5Z)-2,7-Dihydro-1H-azepine-Derived Hamari Ligand for General Asymmetric Synthesis of Tailor-Made Amino Acids

Motohiro Takahashi*^† , Hiroki Moriwaki^†, Toshio Miwa^†, Brittanie Hoang^‡, Peng Wang^‡, and Vadim A. Soloshonok*^§∥ 

^† Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan

^‡ Hamari Chemicals USA, San Diego Research Center, 11494 Sorrento Valley Road, San Diego, California 92121, United States

^§ Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain

^∥ IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, Plaza Bizkaia, 48013 Bilbao, Spain

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00406

Publication Date (Web): January 18, 2019

Copyright © 2019 American Chemical Society

*E-mail: motohiro-takahashi@hamari.co.jp., *E-mail: vadym.soloshonok@ehu.es.

This article is part of the Japanese Society for Process Chemistry special issue.

 

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Kalyan Kumar Pasunooti, 5-Methylisoxazole-3-carboxamide-Directed Palladium-Catalyzed γ-C(sp3)–H Acetoxylation and Application to the Synthesis of γ-Mercapto Amino Acids for Native Chemical Ligation

Palladium-catalyzed acetoxylation of the primary γ-C(sp³)–H bonds in the amino acids Val, Thr, and Ile was achieved using a newly discovered 5-methylisoxazole-3-carboxamide directing group. The γ-acetoxylated α-amino acid derivatives could be easily converted to γ-mercapto amino acids, which are useful for native chemical ligation (NCL). The first application of NCL at isoleucine in the semisynthesis of a Xenopus histone H3 protein was also demonstrated.

5-Methylisoxazole-3-carboxamide-Directed Palladium-Catalyzed γ-C(sp³)–H Acetoxylation and Application to the Synthesis of γ-Mercapto Amino Acids for Native Chemical Ligation

Kalyan Kumar Pasunooti, Renliang Yang, Biplab Banerjee, Terence Yap, and Chuan-Fa Liu^*

School of Biological Sciences, Nanyang Technological University, Singapore 637551

Org. Lett., 2016, 18 (11), pp 2696–2699

DOI: 10.1021/acs.orglett.6b01160

Publication Date (Web): May 24, 2016

Copyright © 2016 American Chemical Society

*E-mail: cfliu@ntu.edu.sg.

link

https://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b01160

hps://pubs.acs.org/doi/suppl/10.1021/acs.orgletttt.6b01160/suppl_file/ol6b01160_si_001.pdf

  

Kalyan Kumar Pasunooti,

Dr. Kalyan Kumar Pasunooti pursued his PhD degree from Nanyang Technological University (NTU) (www.ntu.edu.sg), Singapore (2007 – 2011) in the field of Medicinal, Peptide & Protein chemistry. His graduate research work is focused on “Synthesis of bioactive amino acid building blocks and their applications towards the peptides and glycopeptides.” His have total 16 years of academic and industry experience with major multinationals companies & academic institutions and have worked with many collaborative professors around the globe. He authored with more than 28 international peer-reviewed high impact publications such as PNAS, Wily (Angew Chemie), RSC (Chem Comm and Org Biomol Chem), most of American Chemical Society journals (Journal of American Chemical Society, Org. Lett., ACS Chem Bio, J Comb Chem and Bioconugate Chem) and Elsevier (Tetrahedron Letters) journals which are featured many times in Chem. Eng. News and other journals. He holds American patent while work with Johns Hopkins-School of Medicine, USA and this molecule in phase II clinical trials for treating cancer.

Prior to his graduate studies, he spent 5 years as a research scientist in reputable research organizations namely GVK Bio, India (www.gvkbio.com) (2006-2007) and Dr. Reddy’s Laboratories Ltd (www.drreddys.com) (2003-2006) in India. After his PhD graduation, he worked for world leading research institutes such as Johns Hopkins-School of Medicine, USA (www.hopkinsmedicne.org) (2012-2013), Nanyang Technological University-NTU, Singapore) (www.ntu.edu.sg) (2013 – 2017) and Singapore MIT Alliance for research & Technology-SMART (www.smart.mit.edu) (2017–2018). His research interests focused on development of next generation biologically relevant peptide & protein therapeutics using their newly discovered methodologies for biomedical applications.

He has excellent skills in designing synthesis, purification and characterization of complex peptide and small molecules for medicinal chemistry applications. He gained extensive experience in Medicinal, Carbohydrate, Peptide & Protein and nucleotide & nucleoside Chemistry and familiar with modern methods and experienced in designing & executing synthesis for various bioactive peptide and small molecule inhibitors. He well versed in synthesis and characterization of complex organic molecules and with the analytical data interpretation.

Dr. Kalyan Kumar Pasunooti

Research Scientist at Singapore-MIT Alliance for Research & Technology Centre

Singapore'

Accomplished Peptide, Protein and Medicinal chemist with 16 years of academic and industrialexperience in the field of drug discovery and development. Specializations: Peptide & Protein Chemistry,Medicinal Chemistry (Drug Discovery and Development) and Chemical Biology.

Experience

Research Scientist

Company NameSingapore-MIT Alliance for Research & Technology Centre

Dates EmployedJul 2017 – Present

Employment Duration1 yr 4 mos

LocationSingapore

Medicinal Chemistry and Drug Discovery

Research Fellow

Company NameNanyang Technological University, Singapore

Dates EmployedOct 2013 – Jun 2017

Employment Duration3 yrs 9 mos

LocationSingapore

Peptide & Protein Chemistry and Medicinal Chemistry

Postdoctoral Fellow

Company NameJohns Hopkins Medicine

Dates EmployedMay 2012 – Sep 2013

Employment Duration1 yr 5 mos

LocationBaltimore, Maryland Area

Medicinal chemistry, Drug Discovery, Pharmacology and Chemical Biology

Postdoctoral Associate

Company NameNanyang Technological University

Dates EmployedJul 2011 – Mar 2012

Employment Duration9 mos

LocationSingapore

Organic synthesis, Peptide & Carbohydrate chemistry and Medicinal chemistry.

Senior Research Associate in Medicinal Chemistry

Company NameGVK Biosciences

Dates EmployedJan 2007 – Jul 2007

Employment Duration7 mos

LocationHyderabad Area, India

Synthesis of bioactive molecules for medicinal chemistry applications.

Junior Scientist in Medicinal Chemistry (Anti-Infective group)

Company NameDr. Reddy's Laboratories

Dates EmployedAug 2003 – Dec 2006

Employment Duration3 yrs 5 mos

LocationHyderabad Area, India

Medicinal chemistry (Anti-Infective group): My work entails design and synthesis of newoxazolidinone derivatives and new chemical entities as novel antibacterial agents. As a researchscientist my job demanded me to carry out extensive literature survey to design possible syntheticroutes for a proposed molecule and to carry out the total synthetic part in the laborator... See more

Education

• 

  Nanyang Technological University

  Degree NamePhD

  Field Of StudyOrganic and Bioorganic chemistry

  Dates attended or expected graduation2007 – 2011
• 

  Osmania University

  Degree NameM. Sc

  Field Of StudyPhysical Organic Chemistry

  Dates attended or expected graduation2000 – 2002
• 

  Kakatiya University

  Degree NameB. Sc,

  Field Of StudyMathematics Physics Chemistry

  Dates attended or expected graduation1996 – 1999

 Research Scientist at Singapore-MIT Alliance for Research and Technology

• 
  

  Research Fellow at Nanyang Technological University, Singapore
• 
  

  Former Post-Doctoral Fellow at Johns Hopkins School of Medicine
• 
  

  Studied Physical organic chemistry at PG College of Science, Saifabad/Osmania University
• 
  

  Studied M.P.C at Government Junior College, Hanamkonda
• 
  

  Studied B.Sc. at Kakatiya Government Degree College
• 
  

  Went to Z. P. S. S. Geesugonda

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National award to Anthony Melvin Crasto for contribution to Pharma society from Times Network for Excellence in HEALTHCARE) | 5th July, 2018 | Taj Lands End, Mumbai, India

DR ANTHONY MEVIN CRASTO Conferred prestigious individual national award at function for contribution to Pharma society from Times Network, National Awards for Marketing Excellence ( For Excellence in HEALTHCARE) | 5th July, 2018 | Taj Lands End, Mumbai India

 

////////////National award,  contribution to Pharma society, Times Network, Excellence in HEALTHCARE,  5th July, 2018, Taj Lands End, Mumbai,  India, ANTHONY CRASTO

#hotpersoninawheelchair
#worlddrugtracker

Catalyst-free three-component synthesis of highly functionalized 2,3-dihydropyrroles

Catalyst-free three-component synthesis of highly functionalized 2,3-dihydropyrroles

Dong Wang,a  Linna Li,a  Hairong Feng,a  Hua Sun,a  Fabrice Almeida-Veloso,b  Marine Charavin,b Peng Yua  and  Laurent Désaubry*abc 

 Author affiliations

*Corresponding authors

aSino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
E-mail: desaubry@unistra.fr

bLaboratory of Therapeutic Innovation (UMR 7200), University of Strasbourg-CNRS, Faculty of Pharmacy, 67400 Illkirch, France

cLaboratory of Biomolecules (UMR7203), Sorbonne University – CNRS, 4 place Jussieu, 75005 Paris, France

Abstract

An efficient synthesis of fully substituted 2,3-dihydropyrroles has been achieved in one step through the three-component reaction of amines, aromatic aldehydes and α-ketoamides. This atom-economical and catalyst-free reaction is highly stereoselective and generates underexplored heterocycles in a single step. These compounds were examined in an enzymatic assay that led to the identification of potent α-glucosidase inhibitors, thereby demonstrating the utility of this novel methodology in medicinal chemistry.

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C8GC00987B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

N-(4-Chlorophenyl)-2-oxopropanamide (3a) Cl H N O O 3a Using 4-chloroaniline (1.0 g, 7.8 mmol), in accordance with General Procedure A, the title compound 3a was obtained (810 mg, 52% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 197.1, 157.6, 135.0, 130.6, 129.5, 121.1, 24.2. HRMS (ESI-TOF) m/z calcd. for C9H7NO2Cl- [M-H]- : 196.0171, found 196.0170

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Catalyst-free and solvent-free hydroboration of aldehydes

Green Chem., 2018, Advance Article
DOI: 10.1039/C8GC00042E, Communication

Hanna Stachowiak, Joanna Kazmierczak, Krzysztof Kucinski, Grzegorz Hreczycho
For the first time, a general method for catalyst-free and solvent-free hydroboration of various aldehydes has been developed

Catalyst-free and solvent-free hydroboration of aldehydes

Catalyst-free and solvent-free hydroboration of aldehydes

 

Hanna Stachowiak,^a  Joanna Kaźmierczak,^a  Krzysztof Kuciński^a  and  Grzegorz Hreczycho*^a 

 Author affiliations

*Corresponding authors

^aFaculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61-614 Poznań, Poland
E-mail: g.h@amu.edu.pl

Abstract

A simple catalyst-free and solvent-free method for the hydroboration of various aldehydes bearing a wide array of electron-withdrawing and electron-donating groups was developed. Unlike aldehydes, the addition of boranes to ketones is less efficient and is thus advantageous for the chemoselective reduction of the former ones. It is suggested that the described transformation proceeds with the formation of Lewis acid–base adducts, which facilitates further hydroboration.
4,4,5,5-tetramethyl-2-((4-methylbenzyl)oxy)-1,3,2-dioxaborolane (3b) [1] 4,4,5,5-tetramethyl-2-((4-methylbenzyl)oxy)-1,3,2-dioxaborolane was obtained as colorless oil in 97% yield.
1H NMR (400 MHz, CDCl3) δ (ppm) = 1.29 (s, 12H), 2.36 (s, 3H), 4.91 (s, 2H), 7.17 (d, J = 7.9 Hz, 2H), 7.27-7.30 (m, 2H).
13C NMR (101 MHz, CDCl3) δ (ppm) = 21.3, 24.7, 66.7, 83.0, 127.0, 127.2, 129.1, 129.3, 136.4, 137.1.
11B NMR (128 MHz, CDCl3) δ (ppm) = 22.5.
EA: C14H21BO3 (248.16): calcd.C 67.77; H 8.53; found C 67.66; H 8.47.
 
11B NMR (128 MHz, CDCl3) δ (ppm) = 22.5.

////////////hydroboration

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C8GC00042E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Guest blogger, Dr Pravin Patil, Aryl free radical mediated oxidative arylation of naphthoquinones using o-iodoxybenzoic acid and phenylhydrazines and its application towards synthesis of benzocarbazoledione

J. Org. Chem. 2014, 79 (5), 2331-2336 ; DOI: 10.1021/jo500131h


2-Phenyl-1,4-naphthoquinone 3a. 22 Following the general procedure, the crude product was purified over a silica gel column using a hexane/EtOAc mobile phase (9:1) to give a yellowish solid (140 mg, 60% yield): mp 107−109 °C; 1 H NMR (300 MHz, CDCl3) δ 8.18−8.10 (m, 2H), 7.86−7.75 (m, 2H), 7.56−7.48 (m, 5H), 7.07 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 185.2, 185.1, 148.1, 135.2, 133.9 2-Phenyl-1,4-naphthoquinone 3a. 22 Following the general procedure, the crude product was purified over a silica gel column using a hexane/EtOAc mobile phase (9:1) to give a yellowish solid (140 mg, 60% yield): mp 107−109 °C; 1 H NMR (300 MHz, CDCl3) δ 8.18−8.10 (m, 2H), 7.86−7.75 (m, 2H), 7.56−7.48 (m, 5H), 7.07 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 185.2, 185.1, 148.1, 135.2, 133.9

CONCLUSION

In conclusion, we demonstrated a new method for radical mediated arylation of naphthoquinones using the combination of IBX with arylhydrazines. It does not require necessity of transition metal catalysis and prefunctionalization on naphthoquinone moiety. The reactions occurred under mild conditions in open atmosphere. Further, both 2-hydroxy and 2-amino groups were found to be tolerated under optimized reaction conditions. This fact could be attributed to rapid reaction between IBX and phenyl hydrazine. A postulated radical mediated mechanism was supported by radical trapping experiments. Developed protocols were successfully extended towards an effective, short and high yielding synthesis of benzocarbazoledione. IBX mediated developed protocols for arylation could open a new field in quinone chemistry as well as in the development of new procedures for arylation of electron deficient molecules in near future

Aryl-Free Radical-Mediated Oxidative Arylation of Naphthoquinones Using o-Iodoxybenzoic Acid and Phenylhydrazines and Its Application toward the Synthesis of Benzocarbazoledione

Pravin Patil, Abhay Nimonkar, and Krishnacharya G. Akamanchi*

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India

J. Org. Chem., 2014, 79 (5), pp 2331–2336

DOI: 10.1021/jo500131h

Publication Date (Web): February 10, 2014

Copyright © 2014 American Chemical Society

*E-mail: kgap@rediffmail.com; kg.akamanchi@ictmumbai.edu.in.

http://pubs.acs.org/doi/suppl/10.1021/jo500131h

Abstract

Oxidative arylation of naphthoquinones has been developed through combination of o-iodoxybenzoic acid with arylhydrazines under mild conditions at open atmosphere. Arylated naphthoquinones with different electronic properties were obtained in moderate to good yields. The postulated radical mediated mechanism is supported by radical trapping experiments. Developed protocol for direct arylation of naphthoquinones has been extended toward short, high yielding, and an effective synthesis of antitumor–antibiotic precursor such as benzocarbazoledione.

ABOUT GUEST BLOGGER

Dr. Pravin C. Patil

Postdoctoral Research Associate at University of Louisville

Email, pravinchem@gmail.com

see…….http://oneorganichemistoneday.blogspot.in/2017/04/dr-pravin-patil.html

Dr. Pravin C Patil completed his B.Sc. (Chemistry) at ASC College Chopda (Jalgaon, Maharashtra, India) in 2001 and M.Sc. (Organic Chemistry) at SSVPS’S Science College Dhule in North Maharashtra University (Jalgaon, Maharashtra, India) in year 2003. After M.Sc. degree he was accepted for summer internship training program at Bhabha Atomic Research Center (BARC, Mumbai) in the laboratory of Prof. Subrata Chattopadhyay in Bio-organic Division. In 2003, Dr. Pravin joined to API Pharmaceutical bulk drug company, RPG Life Science (Navi Mumbai, Maharashtra, India) and worked there for two years. In 2005, he enrolled into Ph.D. (Chemistry) program at Institute of Chemical Technology (ICT), Matunga, Mumbai, aharashtra, under the supervision of Prof. K. G. Akamanchi in the department of Pharmaceutical Sciences and Technology.

After finishing Ph.D. in 2010, he joined to Pune (Maharashtra, India) based pharmaceutical industry, Lupin Research Park (LRP) in the department of process development. After spending two years at Lupin as a Research Scientist, he got an opportunity in June 2012 to pursue Postdoctoral studies at Hope College, Holland, MI, USA under the supervision of Prof. Moses Lee. During year 2012-13 he worked on total synthesis of achiral anticancer molecules Duocarmycin and its analogs. In 2014, he joined to Prof. Frederick Luzzio at the Department for Chemistry, University of Louisville, Louisville, KY, USA to pursue postdoctoral studies on NIH sponsored project “ Structure based design and synthesis of Peptidomimetics targeting P. gingivalis.

During his research experience, he has authored 23 international publications in peer reviewed journals and inventor for 4 patents.

Prof K. G. Akamanchi

Prof. K. G. Akamanchi Professor, Pharmaceutical Sciences and Technology Email ID : kg.akamanchi@ictmumbai.edu.in Reseach Area : Development of Novel Methodologies, Hypervalent Iodine Chemistry, Synthesis of drug and drug intermediates, Design and Synthesis of Potential bioactive molecules, Protein Isolation and Bioassay

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