Friday, 1 February 2019

Design, synthesis and antimicrobial activity of usnic acid derivatives

Graphical abstract: Design, synthesis and antimicrobial activity of usnic acid derivatives

Design, synthesis and antimicrobial activity of usnic acid derivatives


Usnic acid, a dibenzofuran, was originally isolated from lichens producing secondary metabolites, and is well known as an antibiotic, but is also endowed with several other interesting properties. Thus, the goal of this paper is the design of new usnic acid derivatives and evaluation of their antimicrobial activity. All newly synthesized compounds possess good antibacterial activity with MIC ranging from 1.02–50.93 × 10−2 mmol mL−1 and MBC from 2.05–70.57 × 10−2 mmol mL−1. The most sensitive bacterial species was Staphylococcus aureus, while Pseudomonas aeruginosa and Escherichia coli were the most resistant among the ATCC strains, and MRSA was the most resistant among all tested bacteria (ATCC and clinical isolates). Their antifungal activity was very strong (MIC = 0.35–7.53 × 10−2 mmol mL−1 and MFC = 0.70–15.05 × 10−2 mmol mL−1) – better than those of reference compounds and usnic acid itself. The most sensitive fungal species was Trichoderma viride, while Penicillium versicolor var. cyclopium appeared to be the most resistant. It should be mentioned that in general most of the compounds showed weaker antibacterial activity, but better antifungal properties than usnic acid itself. The results allow us to conclude that the title compounds are good lead compounds for novel more active antibacterial drugs. On the other hand, these compounds are very promising as antifungals.

Tuesday, 29 January 2019

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

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(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]20D = +173.8° (c = 1.0, CHCl3).

Abstract Image
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
 Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan
 Hamari Chemicals USA, San Diego Research Center11494 Sorrento Valley Road, San Diego, California 92121, United States
§ Department of Organic Chemistry I, Faculty of ChemistryUniversity of the Basque Country UPV/EHUPaseo Manuel Lardizábal 3, 20018 San Sebastián, Spain
 IKERBASQUE, Basque Foundation for ScienceMaría 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
This article is part of the Japanese Society for Process Chemistry special issue.


Sunday, 14 October 2018

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

Abstract Image
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

School of Biological Sciences, Nanyang Technological UniversitySingapore 637551
Org. Lett.201618 (11), pp 2696–2699
DOI: 10.1021/acs.orglett.6b01160
Publication Date (Web): May 24, 2016
Copyright © 2016 American Chemical Society
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Dr. Kalyan Kumar Pasunooti

Kalyan Kumar Pasunooti,

Dr. Kalyan Kumar Pasunooti pursued his PhD degree from Nanyang Technological University (NTU) (, 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 ( (2006-2007) and Dr. Reddy’s Laboratories Ltd ( (2003-2006) in India. After his PhD graduation, he worked for world leading research institutes such as Johns Hopkins-School of Medicine, USA ( (2012-2013), Nanyang Technological University-NTU, Singapore) ( (2013 – 2017) and Singapore MIT Alliance for research & Technology-SMART ( (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


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.

ExperienceSingapore-MIT Alliance for Research & Technology Centre

Research Scientist

  • Company NameSingapore-MIT Alliance for Research & Technology Centre

    Dates EmployedJul 2017 – Present

    Employment Duration1 yr 4 mos


    Medicinal Chemistry and Drug Discovery
  • Research Fellow

    Company NameNanyang Technological University, Singapore

    Dates EmployedOct 2013 – Jun 2017

    Employment Duration3 yrs 9 mos


    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


    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



    Wednesday, 18 July 2018

    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

    times now 1

    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

    times now 5

    times 4

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

    Saturday, 2 June 2018

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

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

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

     Author affiliations


    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.

    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

    Saturday, 31 March 2018

    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

     Author affiliations


    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.

    Thursday, 1 February 2018

    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

    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

    Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India
    J. Org. Chem.201479 (5), pp 2331–2336
    DOI: 10.1021/jo500131h
    Publication Date (Web): February 10, 2014
    Copyright © 2014 American Chemical Society


    Abstract Image
    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.
    Dr. Pravin C. Patil

    Dr. Pravin C. Patil

    Postdoctoral Research Associate at University of Louisville

      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
      ICT Mumbai