הכל על תרופות Tout sur les médicaments كل شيئ عن الأدوية Все о наркотиках 所有关于毒品 డ్రగ్స్ గురించి అన్ని 마약에 관한 모든 것 Όλα για τα Ναρκωτικά Complete Tracking of Drugs Across the World by Dr Anthony Melvin Crasto, worlddrugtracker, PH.D (ICT), MUMBAI, INDIA, Worlddrugtracker, Helping millions, 9 million hits on google on all websites, 2.5 lakh connections on all networks, The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent,
Godfred D. Fianu, Kyle C. Schipper, Robert A. Flowers II
Catalytic amounts of titanocene(III) borohydride, generated under mild conditions from commercially available titanocene dichloride, in concert with a stoichiometric hydride source is shown to effectively reduce aldehydes and ketones to their respective alcohols in aprotic media.
aDepartment of Chemistry, Lehigh University, Bethlehem, USA E-mail:email@example.com
Reduction of a wide range of aldehydes and ketones with catalytic amounts of titanocene borohydride in concert with a stoichiometric poly(methylhydrosiloxane) (PMHS) reductant is reported. Preliminary mechanistic studies demonstrate that the reaction is mediated by a reactive titanocene(III) complex, whose oxidation state remains constant throughout the reaction.
Phenyl methanol (2-c)
Phenyl methanol (2-c) was prepared from benzaldehyde (1-c) by the procedure outlined
in GP1. NMR analysis showed 100% conversion in 1 hour. 86% isolated yield of alcohol
product was obtained after complete workup.
Metal-catalyzed cycloadditions of alkenyldiazo reagents are useful tools to access carbo- and heterocycles. These diazo compounds are chemically sensitive toward both Brønsted orLewis acids. Their reported cycloadditions rely heavily on the formation of metal carbenes to initiate regio- and stereoselective [3+n] cycloadditions (n=2–4) with suitable dipolarophiles.[2–4] A noncarbene route was postulated for a few copper-catalyzed cycloadditions of these diazo species, but they resulted in complete diazo decomposition.[3a, 4a, 5] oyle and co-workers reported[4a] a [3+2] cycloaddition of the alkenylrhodium carbene A with imines to give dihydropyrroles (Scheme 1a). We proposed a cycloaddition the tetrahydroquinoline derivatives 3 and 3’, as well as the tetrahydro-1H-benzo[b]azepine species 4. Access to these frameworks are valuable
Access to these frameworks are valuable for the preparation of several bioactive molecules including 2-phenyl-2,3-
dihydroquinolone,[8a] L-689,560,[8b] torcetrapib,[8c] martinellic acid,[8d] OPC-31260,[8e] OPC-51803,[8f] and tetraperalone A (Figure 1).[8g] Their specific biological functions have been well documented.
Spectral data for ethyl 2-diazo-2-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl) acetate (2a)
†We thank the National Science Council, Taiwan, for financial support of this work., [*] A. M. Jadhav, V. V. Pagar, Prof. Dr. R.-S. Liu
Department of Chemistry, National Tsing Hua University
Hsinchu (30013) (Taiwan)
Rings aplenty: A HOTf-catalyzed (Tf=trifluoromethanesulfonyl) Povarov reaction of alkenyldiazo species has been developed and delivers diazo-containing cycloadducts stereoselectively (see scheme). The resulting cycloadducts provide access to six- and seven-membered azacycles through the generation of metal carbenes as well as the functionalization of diazo group.
 Selected reviews: a) M. P. Doyle,M. A. McKervy, T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds, Wiley, New York, 1998; b) A. Padwa, M. D. Weingarten, Chem. Rev. 1996, 96, 223; c) H. M. L. Davies, J. R. Denton, Chem. Soc. Rev. 2009, 38, 3061; d) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010, 110, 704; e) H. M. L. Davies, D. Morton, Chem. Soc. Rev. 2011, 40, 1857; f) Z. Zhang, J. Wang, Tetrahedron
2008, 64, 6577.
 Selected examples for carbocyclic cycloadducts, see: a) L. Deng, A. J. Giessert, O. O. Gerlitz, X. Dai, S. T. Diver, H. M. L. Davies, J. Am. Chem. Soc. 2005, 127, 1342; b) H. M. L. Davies, Adv. Cycloaddit. 1999, 5, 119; c) H. M. L. Davies, B. Xing, N. Kong, D. G. Stafford, J. Am. Chem. Soc. 2001, 123, 7461; d) H. M. L. Davies, T. J. Clark, H. D. Smith, J. Org. Chem. 1991, 56, 3819; e) Y. Liu, K. Bakshi, P. Zavalij, M. P. Doyle, Org. Lett. 2010, 12, 4304; f) J. P. Olson, H. M. L. Davies, Org. Lett. 2008, 10, 573.
 For oxacyclic cycloadducts, see: a) X. Xu, W.-H. Hu, P. Y. Zavalij, M. P. Doyle, Angew. Chem. 2011, 123, 11348; Angew. Chem. Int. Ed. 2011, 50, 11152; b) M. P. Doyle, W. Hu, D. J. Timmons, Org. Lett. 2001, 3, 3741.
 For azacyclic cycloadducts, see selected reviews: a) M. P. Doyle, M. Yan, W. Hu, L. Gronenberg, J. Am. Chem. Soc. 2003, 125, 4692; b) J. Barluenga, G. Lonzi, L. Riesgo, L. A. Lpez, M. Tomas, J. Am. Chem. Soc. 2010, 132, 13200; c) M. Yan, N. Jacobsen, W. Hu, L. S. Gronenberg, M. P. Doyle, J. T. Colyer, D. Bykowski, Angew. Chem. 2004, 116, 6881; Angew. Chem. Int. Ed. 2004, 43, 6713; d) X.Wang, X. Xu, P. Zavalij, M. P. Doyle, J. Am.
Chem. Soc. 2011, 133, 16402; e) Y. Lian, H. M. L. Davies, J. Am. Chem. Soc. 2010, 132, 440; f) X. Xu, M. O. Ratnikov, P. Y. Zavalij, M. P. Doyle, Org. Lett. 2011, 13, 6122; g) V. V. Pagar, A. M. Jadhav, R.-S. Liu, J. Am. Chem. Soc. 2011, 133, 20728; h) R. P. Reddy, H. M. L. Davies, J. Am. Chem. Soc. 2007, 129, 10312.
 Y. Qian, X. Xu, X.Wang, P. Zavalij,W. Hu, M. P. Doyle, Angew. Chem. 2012, 124, 6002; Angew. Chem. Int. Ed. 2012, 51, 5900.
 Povarov reactions refer to the formal [4+2] cycloadditions of Naryl imines with enol ethers or enamines. See reviews: a) L. S. Povarov, Russ. Chem. Rev. 1967, 36, 656; b) V. V. Kouznetsov, Tetrahedron 2009, 65, 2721; c) D. Bello, R. Ramn, R. Lavilla, Curr. Org. Chem. 2010, 14, 332; d) M. A. McCarrick, Y. D. Wu, K. N. Houk, J. Org. Chem. 1993, 58, 3330; e) A. Whiting, C. M. Windsor, Tetrahedron 1998, 54, 6035.
 For Povarov reactions catalyzed by Brønsted acids, see selected examples: a) H. Xu, S. J. Zuend, M. G. Woll, Y. Tao, E. N. Jacobson, Science 2010, 327, 986; b) T. Akiyama, H. Morita, K. Fuchibe, J. Am. Chem. Soc. 2006, 128, 13070; c) H. Liu, G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am. Chem. Soc. 2009, 131, 4598; d) G. Dagousset, J. Zhu, G. Masson, J. Am. Chem. Soc. 2011, 133, 14804; e) H. Ishitani, S. Kobayashi, Tetrahedron Lett. 1996, 37, 7357; f) G. Bergonzini, L. Gramigna, A. Mazzanti, M. Fochi, L. Bernardi, A. Ricci, Chem. Commun.
2010, 46, 327; g) L. He, M. Bekkaye, P. Retailleau, G. Masson, Org. Lett. 2012, 14, 3158.
 a) Y. Xia, Z.-Y. Yang, P. Xia, K. F. Bastow, Y. Tachibana, S.-C. Kuo, E. Hamel, T. Hackl, K.-H. Lee, J. Med. Chem. 1998, 41, 1155; b) R.W. Carling, P. D. Leeson, A. M. Moseley, J. D. Smith, K. Saywell, M. D. Trickelbank, J. A. Kemp, G. R. Marshall, A. C. Foster, S. Grimwood, Bioorg. Med. Chem. Lett. 1993, 3, 65;
c) D. B. Damon, R. W. Dugger, R.W. Scott, U.S. Patent 6,689,897, 2004; d) D. A. Powell, R. A. Batey, Org. Lett. 2002, 4, 2913; e) A. Matsuhisa, K. Kikuchi, K. Sakamoto, T. Yatsu, A. Tanaka, Chem. Pharm. Bull. 1999, 47, 329; f) M. Y. Christopher, E. A. Christine, D. M. Ashworth, J. Barnett, A. J. Baxter, J. D. Broadbridge, R. J. Franklin, S. L. Hampton, P. Hudson, J. A. Horton, P. D. Jenkins, A. M. Penson, G. R.W. Pitt, P. Rivire,
P. A. Robson, D. P. Rooker, G. Semple, A. Sheppard, R. M.Haigh, M. B. Roe, J. Med. Chem. 2008, 51, 8124; g) C. Li, X. Li, R. Hong, Org. Lett. 2009, 11, 4036.
About author( Me)
Dr. Vinayak Pagar
Postdoctoral Research Fellow at The Ohio State University
Vinayak Vishnu Pagar was born in Nasik, Maharashtra (India) in 1983. He obtained his BSc and MSc degrees in chemistry from the University of Pune (India) in 2004 and 2006, respectively. From 2006–2010, he worked as Research Associate in pharmaceutical companies like Jubilant Chemsys Ltd. and Ranbaxy Laboratories Ltd. (India). In 2010, he joined the group of Professor Rai-Shung Liu to pursue his PhD degree in National Tsing Hua University (Taiwan) and completed it in 2014. Subsequently, he worked as a postdoctoral fellow in the same group for one year. Currently, he is working as a Research Scientist at The Ohio State University, Columbus, Ohio USA. His research focused on the development of new organic reactions by using transition-metal catalysis such Gold, Silver, Rhodium, Zinc, Cobalt, Nickel and Copper metals which enables mild, diastereoselective, enantioselective and efficient transformations of variety of readily available substrates to wide range of synthetically useful nitrogen and oxygen containing heterocyclic products which are medicinally important. He published his research in a very high impact factor international Journals includes J. Am. Chem. Soc., Angew. Chem. Int. Ed.,J. Org. Chem., Chem- A. Eur. Journal, Org. Biomol. Chem., and Synform (Literature Coverage).
Katharina J. Hock, Robin Spitzner, Rene M. Koenigs
Applications of diazo acetonitrile in cyclopropa(e)nation reactions are realized in a slow-release protocol with bench-stable reagents. Cyclopropyl nitriles are obtained in one step in good diastereoselectivity on a gram-scale providing an efficient entry into this class of fragrances and drug-like molecules.
Diazo acetonitrile has long been neglected despite its high value in organic synthesis due to a high risk of explosions. Herein, we report our efforts towards the transient and safe generation of this diazo compound, its applications in iron catalyzed cyclopropanation and cyclopropenation reactions and the gram-scale synthesis of cyclopropyl nitriles.
A Baeyer–Villiger monooxygenase enzyme has been used to manufacture a chiral sulfoxide drug intermediate on a kilogram scale. This paper describes the evolution of the biocatalytic manufacturing process from the initial enzyme screen, development of a kilo lab process, to further optimization for plant scale manufacture. Efficient gas–liquid mass transfer of oxygen is key to obtaining a high yield.
Development and Scale-up of a Biocatalytic Process To Form a Chiral Sulfoxide
[ ] 20 a D = -381.9 (c 1.0 in EtOH) for (1R,2R)-3, ee = 95%
In this study a batch reactor process is compared to a flow chemistry approach for lipase-catalyzed resolution of the cyclopropanecarboxylate ester (±)-3. (1R,2R)-3 is a precursor of the amine (1R,2S)-2 which is a key building block of the API ticagrelor. For both flow and batch operation, the biocatalyst could be recycled several times, whereas in the case of the flow process the reaction time was significantly reduced.
Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor
TOFMS: [C13H21NO6 – H+]: calculated 286.1296, found 286.1031(100%).
HPLC conditions were as follows for compound ; Agilent 1100 series, column: YMC J’SPHERE C18 (150 mm X 4.6 mm) 4µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 210 nm, flow was set at 1.0 mL/min, and the temperature was 30 °C (Run time: 45 min). Gradient: 0 min, A = 90%, B = 10%; 5.0 min, A = 90%, B = 10%; 25 min, A = 0%, B = 100%; 30 min, A = 0%, B = 100%, 35 min, A = 90%, B = 10%; 45 min, A = 90%, B = 10%.
TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).
UPLC conditions were as follows for compound 11; Acquity Waters, column: BEH C18 (2.1 mm X 100 mm) 1.7 µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 220 nm, flow was set at 0.4 mL/min, and the temperature was 30 °C (Run time: 9 min). Gradient: 0 min, A = 90%, B = 10%; 0.5 min, A = 90%, B = 10%; 6.0 min, A = 0%, B = 100%; 7.5 min, A = 0%, B = 100%; 7.6 min, A = 90%, B = 10%; 9.0 min, A = 90%, B = 10%.
Hana and co-workers ( Synlett 2010, 18, 2759−2764) from Genentech have developed a single-step procedure for conversion of 2-nitro aromatic amines to benzimidazoles. Addition of ammonium chloride proved necessary as Fe powder and formic acid alone was ineffective for nitro reduction. These conditions were compatible with a variety of functional groups on the aromatic, including boronate esters. The methodology was also extended to nitro aminopyridines but failed to deliver the desired product with isoxazole or pyrazole reactants.
Mild and General One-Pot Reduction and Cyclization of Aromatic and Heteroaromatic 2-Nitroamines to Bicyclic 2H-Imidazoles
Emily J. Hanan*, Bryan K. Chan, Anthony A. Estrada, Daniel G. Shore, Joseph P. Lyssikatos
*Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA, Email: hanan.emilygene.com
E. J. Hanan, B. K. Chan, A. A. Estrada, D. G. Shore, J. P. Lyssikatos, Synlett, 2010, 2759-2764.
A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles employs formic acid, iron powder, and NH4Cl as additive to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functional groups demonstrates the general utility of this procedure.
We have reported herein a catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles by which a series of five-ring-fused tetrahydroisoquinolines featuring an indoline scaffold were obtained as single diastereomers in moderate to high yields without any additives under mild conditions. Moreover, the current method provides a novel and convenient approach for the efficient incorporation of two biologically important scaffolds (tetrahydroisoquinoline and indoline).
One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases
Green Chem., 2017, Advance Article DOI: 10.1039/C6GC03023H, Communication
P. Matzel, M. Gand, M. Hohne
Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines.
One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases
Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines. In this work, we explored this potential and synthesized the pharmaceutically relevant (R)-rasagiline in high yields (up to 81%) and good enantiomeric excess (up to 90% ee) from the ketone precursor. This one-step approach in aqueous medium represents the shortest synthesis route from achiral starting materials. Furthermore, we demonstrate for the first time that tertiary amines also can be accessed by this route, which provides new opportunities for eco-friendly enzymatic asymmetric syntheses of these important molecules.