IT IS NOW OR NEVER; FOR ENHANCED RESEARCH COLLABORATION, NAY, PARTNERSHIPS BETWEEN INDUSTRY AND INSTITUTES/ACADEMIA

Pens have gone dry and words have run out, highlighting the need for Industry-Academia collaboration. However, it is indeed deeply dismaying that very little progress has been made in “building the bridges” we have been advocating and promoting over the last few decades, when the necessity and urgency of innovative research leading to IP/Patent protection and technology licensing is recognised as a priority. Except for couple of pockets of excellence, there have been very few “box office” hits to write about. One example to quote is the Venture Centre at the NCL (National Chemical Laboratory, Pune) headed by Dr. V. Premnath. A few exceptional achievements in a relatively short time by this innovation/start up incubation centre are worth taking note of.

Resources or Capabilities: A Study of Startup Emergence within Applied Research Universities in India

Over the past decade, the Indian entrepreneurial ecosystem has witnessed a steep growth in the number of incubators within academic environments. While most of these have focused on provision of tangible and intangible resources, the understanding about processes and routines that transform these resources into capabilities, which ultimately translate into successful start-up emergence has been lacking. Based on the resource-based view and the dynamic capabilities approach and using the cases of two academic incubators in India (Indian Institute of Technology, Madras and National Chemical Laboratory, Pune), this paper analyses the pre-incubation level processes that have resulted in their enhanced opportunity recognition potential. This study adds to the literature in the area of dynamic capabilities in the context of academic incubation. The study has important implications for both incubation setups as well as policy makers.

Optimization of IBA for Efficient Survival of Micropropagated Garcinia indica Choisy Shoots Using in-vitro and ex-vitro Rooting Techniques

Aims: The study focuses on optimization of concentration and time of rooting hormone exposure of IBA (Indole-3-Butyric Acid) for efficient survival of tissue culture raised Garcinia indica Choisy plantlets for in-vitro and ex-vitro rooting techniques. Study Design: The subcultured microshoots of Garcinia indica were subjected to in-vitro and ex-vitro rooting trials by treating them with IBA of varying concentration and time, to standardize these particular parameters required by this auxin to induce rooting. Place and Duration of Study: Rooting trials were carried out in Plant tissue culture-Biochemical Sciences Division of CSIR- National Chemical Laboratory, Pune 411008 between June 2018 and April 2019. Methodology: Regularly subcultured five to six years old shoots from female trees of Garcinia indica were used for the study. Various concentrations of IBA in correlation with time were used for in-vitro and ex-vitro root induction. The rooted plantlets were then transferred to polyhouse for acclimatization and will further be planted in open field locations in June 2019. Results: Induction of rooting was observed within thirty days of treatment with IBA. It was observed that 500ppm of IBA gave 30% rooting for in-vitro rooting trials whereas 2000ppm of IBA induced 80% rooting for shoots given ex-vitro rooting treatments. An interesting phenomenon that was observed for 70% of the shoots which failed to induce rooting by in-vitro treatment was that they survived with 100% rooting success under ex-vitro rooting conditions. The hardened plantlets were successfully acclimatized in the polyhouse with survival rate of 90% and were further transferred to polythene bags with rooting mixtures of sand: farmyard manure: coco peat (1:1:2). These plantlets have been healthy for the last 6 to 9 months and will be transported for field trials in June 2019. Conclusion: Ex-vitro rooting technique was found to be more effective than in-vitro rooting. Thus, by optimizing the rooting hormone parameters, female plants of Garcinia indica can be successfully grown using tissue culture technology and can be propagated in large numbers to increase the female plant number in plantations.

Mesoporous carbon and microporous zeolite supported Ru catalysts for selective levulinic acid hydrogenation into γ-valerolactone

Ru supported on mesoporous carbon Sibunit and microporous zeolites (HZSM-5, SiO2/Al2O3 = 250; H-Beta, SiO2/Al2O3 = 30; H-Y, SiO2/Al2O3 = 5; H-USY, SiO2/Al2O3 = 30) synthesized by the sol-gel method (CSIR-National Chemical Laboratory, Pune India) were prepared by impregnation of the corresponding supports with RuCl3∙nH2O (0.1 M) followed by reduction in H2. Catalyst screening in levulinic acid (LA) (15 mL, 6.9 mmol) hydrogenation into g-valerolactone (GVL) with 1,4-dioxane (165°C, hydrogen pressure ca. 16 bar) as a solvent showed higher activity and selectivity to GVL of Ru/zeolites compared to carbon supported catalysts. Among Ru/zeolites LA conversion increased as follows Ru/HZSM-5 < Ru/H-Y < Ru/H-USY < Ru/H-Beta demonstrating a clear advantage of H-Beta preparation method. Optimization of the support microstructure and acidity opens a reliable way for selective catalytic LA hydrogenation to GVL. The catalysts were analyzed by TEM, XRD, H2-TPR and N2 physisorption to compare their physical chemical properties.

Screening of N-Benzoyl Isoserine Methyl Ester (N-bime) for anti-inflammatory analgesic activity and toxicity profile in animals

Background: Pain and inflammation are the basic processes involved in the pathogenesis of many diseases. Non-steroidal anti-inflammatory drugs are often used to treat rheumatic diseases. The study compound N-Benzoyl Isoserine Methyl Ester (N-bime) is a newly synthesized propionic acid derivative by National Chemical Laboratory, Pune. Since the biological data of this compound is not available, the present study has been planned to screen this compound for anti-inflammatory, analgesic activity and its toxicity profile in animals.Methods: Single dose toxicity study was carried out in rats. Anti-inflammatory activity was tested by Rat Hind Paw Oedema and Cotton Pellet Implantation method. For Analgesic activity, Acetic acid induced writhing and Tail Pinch method was used. Yeast induced Pyrexia was used for evaluation of anti-pyretic activity. Ibuprofen was the positive control. Data are presented as mean±SEM. Statistical analysis was performed by analysis of variance and students unpaired‘t’ test.Results: The test compound N-bime did not show any apparent adverse effects or mortality in the dose range 1mg - 500mg / 100gm body weight in animals. It showed better anti-inflammatory actions in higher doses as compared to Ibuprofen (p˂ 0.05). In acetic acid induced writhing test N-bime offered better protection against writhes, than Ibuprofen. But, both failed to demonstrate analgesic activity in the Tail Pinch method. N-bime showed a gradual decrease in temperature in the anti-pyretic test (P<0.001).Conclusions: The present study indicates that N-bime does possess anti-inflammatory, analgesic and weak anti-pyretic properties like the NSAIDs. It has proved to be safe in the dose range of 1mg - 500mg / 100gm body weight in rats and mice.

Organocatalyzed C–C Ring Construction: The Mihovilovic Synthesis of Piperenol B

M. Kevin Brown of Indiana University prepared (J. Am. Chem. Soc. 2015, 137, 3482) the cyclobutane 3 by the organocatalyzed addition of 2 to the alkene 1. Karl Anker Jørgensen of Aarhus University assembled (J. Am. Chem. Soc. 2015, 137, 1685) the complex cyclobutane 7 by the addition of 5 to the acceptor 4, followed by conden­sation with the phosphorane 6. Zhi Li of the National University of Singapore balanced (ACS Catal. 2015, 5, 51) three enzymes to effect enantioselective opening of the epoxide 8 followed by air oxidation to 9. Gang Zhao of the Shanghai Institute of Organic Chemistry and Zhong Li of the East China University of Science and Technology added (Org. Lett. 2015, 17, 688) 10 to 11 to give 12 in high ee. Akkattu T. Biju of the National Chemical Laboratory combined (Chem. Commun. 2015, 51, 9559) 13 with 14 to give the β-lactone 15. Paul Ha-Yeon Cheong of Oregon State University and Karl A. Scheidt of Northwestern University reported (Chem. Commun. 2015, 51, 2690) related results. Dieter Enders of RWTH Aachen University constructed (Chem. Eur. J. 2015, 21, 1004) the complex cyclopentane 20 by the controlled com­bination of 16, 17, and 18, followed by addition of the phosphorane 19. Derek R. Boyd and Paul J. Stevenson of Queen’s University Belfast showed (J. Org. Chem. 2015, 80, 3429) that the product from the microbial oxidation of 21 could be protected as the acetonide 22. Ignacio Carrera of the Universidad de la República described (Org. Lett. 2015, 17, 684) the related oxidation of benzyl azide (not illustrated). Manfred T. Reetz of the Max-Planck-Institut für Kohlenforschung and the Philipps-Universität Marburg found (Angew. Chem. Int. Ed. 2014, 53, 8659) that cytochrome P450 could oxidize the cyclohexane 23 to the cyclohexanol 24. F. Dean Toste of the University of California, Berkeley aminated (J. Am. Chem. Soc. 2015, 137, 3205) the ketone 25 with 26 to give 27. Benjamin List, also of the Max-Planck-Institut für Kohlenforschung, reported (Synlett 2015, 26, 1413) a parallel investigation. Philip Kraft of Givaudan Schweiz AG and Professor List added (Angew. Chem. Int. Ed. 2015, 54, 1960) 28 to 29 to give 30 in high ee.

Diels–Alder Cycloaddition: Pancratistatin (Cho), Nootkatone (Reddy), Platensimycin (Zhang/Lee), Scabronine G (Nakada), Isoglaziovianol (Trauner)

Samuel J. Danishefsky of Columbia University and the Memorial Sloan-Kettering Cancer Center made (Proc. Natl. Acad. Sci. 2013, 110, 10904) the unexpected obser­vation that methylation of the enolate derived from conjugate addition to the readily-prepared 1 followed by intramolecular alkene metathesis led to the trans fused ketone 2. This can be contrasted to the diastereo- and regioisomer 3, the product from Diels-Alder cycloaddition of 2-methylcyclohexenone to isoprene. The trans ring fusion of 2 is particularly significant because ozonolysis followed by aldol condensation would deliver the angularly-methylated trans-fused 6/5 C–D ring system of the steroids and related natural products. Cheon-Gyu Cho of Hanyang University added (Org. Lett. 2013, 15, 5806) the activated dienophile 4 to the dienyl lactone to give, after oxidation, the dibro­mide 5. Debromination followed by oxidation led to the antineoplastic lactam pancratistatin 6. D. Srinivasa Reddy of CSIR-National Chemical Laboratory Pune devised (J. Org. Chem. 2013, 78, 8149) a cascade protocol of Diels-Alder cycloaddition of 8 to the diene 7, followed by intramolecular aldol condensation, to give the enone 9. Oxidative manipulation followed by methylenation completed the synthesis of the commercially important grapefruit flavor nootkatone 10. Xinhao Zhang and Chi-Sing Lee of the Peking University Shenzen Graduate School uncovered (J. Org. Chem. 2013, 78, 7912) another cascade transformation, intermolecular addition of 11 to 12 followed by intramolecular Conia-ene cyclization, to give the tricyclic 13. Further manipulation led to an established intermediate for the total synthesis of platensimycin 14. Masahisa Nakada of Waseda University prepared (Angew. Chem. Int. Ed. 2013, 52, 7569) the enantiomerically-pure allene 15. Oxidation of the phenol to the monoketal of the cyclohexadienone set the stage for intramolecular cycloaddition to give 16. Oxidative cleavage followed by intramolecular alkene metathesis led to (+)-scabronine G 17. Dirk Trauner of the University of Munich assembled (Org. Lett. 2013, 15, 4324) the enantiomerically-pure alcohol 18. Oxidation gave the quinone, leading to intra­molecular Diels–Alder cycloaddition. The free alcohol then added to the exocyclic alkene of that product, to give, after further oxidation, the ether 19. Deprotection fol­lowed by reduction then completed the synthesis of (−)-isoglaziovianol 20.

Organocatalyzed C–C Ring Construction: The Bradshaw/Bonjoch Synthesis of (−)-Cermizine B

In a continuation of his studies (OHL20141229, OHL20140811) of organocatalyzed 2+2 photocycloaddition, Thorsten Bach of the Technische Universität München assembled (Angew. Chem. Int. Ed. 2014, 53, 7661) 3 by adding 2 to 1. Li-Xin Wang of the Chengdu Institute of Organic Chemistry also used (Org. Lett. 2014, 16, 6436) an organocatalyst to effect the addition of 5 to 4 to give 6. Shuichi Nakamura of the Nagoya Institute of Technology devised (Org. Lett. 2014, 16, 4452) an organocatalyst that mediated the enantioselective opening of the aziridine 7 to 8. Zhi Li of the National University of Singapore cloned (Chem. Commun. 2014, 50, 9729) an enzyme from Acinetobacter sp. RS1 that reduced 9 to 10. Gregory C. Fu of Caltech developed (Angew. Chem. Int. Ed. 2014, 53, 13183) a phosphine catalyst that directed the addition of 12 to 11 to give 13. Armido Studer of the Westfälische Wilhelms-Universität Münster showed (Angew. Chem. Int. Ed. 2014, 53, 9622) that 15 could be added to 14 to give 16 in high ee. Akkattu T. Biju of CSIR-National Chemical Laboratory described (Chem. Commun. 2014, 50, 14539) related results. The photostimulated enantioselective ketone alkylation developed (Chem. Sci. 2014, 5, 2438) by Paolo Melchiorre of ICIQ was powerful enough to enable the alkyl­ation of 17 with 18 to give 19, overcoming the stereoelectronic preference for axial bond formation. David W. Lupton of Monash University established (J. Am. Chem. Soc. 2014, 136, 14397) the organocatalyzed transformation of the dienyl ester 20 to 21. James McNulty of McMaster University added (Angew. Chem. Int. Ed. 2014, 53, 8450) azido acetone 23 to 22 to give 24 in high ee. There are sixteen enantiomerically-pure diastereomers of the product 27. John C.-G. Zhao of the University of Texas at San Antonio showed (Angew. Chem. Int. Ed. 2014, 53, 7619) that with the proper choice of organocatalyst, with or without subsequent epimerization, it was possible to selectively prepare any one of eight of those diastereomers by the addition of 26 to 25. William P. Malachowski of Bryn Mawr College showed (Tetrahedron Lett. 2014, 55, 4616) that 28, readily prepared by a Birch reduction protocol, was converted by heating followed by exposure to catalytic Me3P to the angularly-substituted octalone 29.

C–N Ring Construction: The Hattori Synthesis of (+)-Spectaline

Magnus Rueping of RWTH Aachen University found (Chem. Commun. 2015, 51, 2111) that under Fe catalysis, a Grignard reagent would couple with the iodoazetidine 1 to give the substituted azetidine 2. Timothy F. Jamison of MIT established (Chem. Eur. J. 2015, 21, 7379) a protocol for converting 3, readily available from commercial homoserine lactone, to the alkylated azetidine 4. Long-Wu Ye of Xiamen University used (Chem. Commun. 2015, 51, 2126) a gold catalyst to cyclize 5, readily prepared in high ee, to the versatile ene sulfonamide 6. Chang- Hua Ding and Xue-Long Hou of the Shanghai Institute of Organic Chemistry added (Angew. Chem. Int. Ed. 2015, 54, 1604) the racemic aziridine 7 to the enone 8 to give the pyrrolidine 9 in high ee. Arumugam Sudalai of the National Chemical Laboratory employed (J. Org. Chem. 2015, 80, 2024) proline as an organocatalyst to mediate the addition of 11 to 10, leading to the pyrrolidine 12. Aaron D. Sadow of Iowa State University developed (J. Am. Chem. Soc. 2015, 137, 425) a Zr catalyst for the enantioselective cyclization of the prochiral 13 to 14. Masahiro Murakami of Kyoto University devised (Angew. Chem. Int. Ed. 2015, 54, 7418) a Rh catalyst for the enantioselective ring expansion of the photocycliza­tion product of 15 to the enamine 16. Sebastian Stecko and Bartlomiej Furman of the Polish Academy of Sciences reduced (J. Org. Chem. 2015, 80, 3621) the carbohydrate-derived lactam 17 with the Schwartz reagent to give an intermediate that could be coupled with an isonitrile, leading to the amide 18. Lei Liu of Shandong University oxidized (Angew. Chem. Int. Ed. 2015, 54, 6012) the alkene 19 in the presence of 20 to give 21. Tomislav Rovis of Colorado State University optimized (J. Am. Chem. Soc. 2015, 137, 4445) a Zn catalyst for the addition of 22 to the nitro alkene 23, leading, after reduction, to the piperidine 24. Carlos del Pozo and Santos Fustero of the Universidad de Valencia used (Org. Lett. 2015, 17, 960) a chiral auxiliary to direct the cyclization of 25 to the bicyclic amine 26. In another illustration of the use of microwave irradiation to activate amide bond rotation, G. Maayan of Technion showed (Org. Lett. 2015, 17, 2110) that 27 could be cyclized efficiently to the medium ring lactam 28.

Reactions of Alkenes: The Usami Synthesis of (−)-Pericosine E

Dasheng Leow of the National Tsing Hua University used (Eur. J. Org. Chem. 2014, 7347) photolysis to activate the air oxidation of hydrazine to generate diimide, that then reduced 1 selectively to 2. Kevin M. Peese of Bristol-Myers Squibb effected (Org. Lett. 2014, 16, 4444) ring-closing metathesis of 3 followed by in situ reduction to form 4. Jitendra K. Bera of the Indian Institute of Technology Kanpur effected (J. Am. Chem. Soc. 2014, 136, 13987) gentle oxidative cleavage of cyclooctene 5 to the dialde­hyde 6. Arumugam Sudalai of the National Chemical Laboratory observed (Org. Lett. 2014, 16, 5674) high regioselectivity in the oxidation of the alkene 7 to the ketone 8. Hao Xu of Georgia State University also observed (J. Am. Chem. Soc. 2014, 136, 13186) high regioselectivity in the oxidation of the alkene 9 with 10, leading to the urethane 11. Justin Du Bois of Stanford University developed (J. Am. Chem. Soc. 2014, 136, 13506) mild conditions for the net double amination of the alkene 12 with 13, leading to 14. Jiaxi Xu and Pingfan Li of the Beijing University of Chemical Technology devised (Org. Lett. 2014, 16, 6036) a protocol for the allylic thiomethylation of an alkene with 16, converting 15 to 17. Matthias Beller of the Leibniz-Institüt für Katalyse combined (Chem. Eur. J. 2014, 20, 15692) hydroformylation, aldol condensation, and reduction to convert the alkene 18 to the ketone 19. Phil S. Baran of Scripps/La Jolla added (Angew. Chem. Int. Ed. 2014, 53, 14382) the diazo dienone 21 to the alkene 20 to give, after exposure to HCl, the arylated product 22. Markus R. Heinrich of the Friedrich-Alexander-Universität Erlangen-Nürnberg employed (Chem. Eur. J. 2014, 20, 15344) Selectfluor as both an oxidizing and a fluorinating agent in the related addition of 24 to 23 to give 25. Debabrata Maiti at the Indian Institute of Technology Bombay activated (J. Am. Chem. Soc. 2014, 136, 13602) the ortho position of 27, then added that interme­diate to 26 to give 28.