Tout sur les médicaments הכל על תרופות كل شيئ عن الأدوية Все о наркотиках 关于药品的一切 డ్రగ్స్ గురించి అన్ని 마약에 관한 모든 것 Όλα για τα Ναρκωτικά Complete Tracking of Drugs Across the World by Dr Anthony Melvin Crasto, Worldpeacepeaker, worlddrugtracker, PH.D (ICT), MUMBAI, INDIA, Worlddrugtracker, Helping millions, 9 million hits on google on all websites, 2.5 lakh connections on all networks, “ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent
PROCESS, spectroscopy, SYNTHESISComments Off on A Fully Continuous-Flow Process for the Synthesis of p-Cresol: Impurity Analysis and Process Optimization
A fully continuous-flow diazotization–hydrolysis protocol has been developed for the preparation of p-cresol. This process started from the diazotization of p-toluidine to form diazonium intermediate. The reaction was then quenched by urea and subsequently followed by a hydrolysis to give the final product p-cresol. Three types of byproducts were initially found in this reaction sequence. After an optimization of reaction conditions (based on impurity analysis), side reactions were eminently inhibited, and a total yield up to 91% were ultimately obtained with a productivity of 388 g/h. The continuous-flow methodology was used to avoid accumulation of the highly energetic and potentially explosive diazonium salt to realize the safe preparation for p-cresol.
†National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, ‡Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. China
spectroscopy, SYNTHESISComments Off on Catalyst-free multi-component cascade C-H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines
Catalyst-free multi-component cascade C-H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines
Green Chem., 2017, 19,4036-4042 DOI: 10.1039/C7GC01494E, Communication
Mohit L. Deb, Choitanya D. Pegu, Paran J. Borpatra, Prakash J. Saikia, Pranjal K. Baruah
Synthesis of 1,3-oxazines via catalyst free C-H functionalization using molecular oxygen in water.
Catalyst-free multi-component cascade C–H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines
bAnalytical chemistry division, CSIR-NEIST, Jorhat-785006, India
Abstract
Herein, catalyst-free 3-component reactions of naphthols, aldehydes, and tetrahydroisoquinolines to synthesize 1,3-oxazines is reported. The reaction is performed in H2O in the presence of O2 as the sole oxidant at 100 °C, which proceeds through the formation of 1-aminoalkyl-2-naphthols followed by selective α-C–H functionalization of tert-amine.
HRMS (ESI) exact mass calculated for C26H21NO [M+H]+ : 364.1701; found: 364.1705.
The representative procedure for the synthesis of 4a is as follows: 2-naphthol (1a, 144 mg, 1 mmol), benzaldehyde (2a, 106 mg, 1 mmol), tetrahydroisoquinoline (3, 133 mg, 1 mmol) and water (1.5 mL) were added in a round-bottom flask equipped with a magnetic stirring bar and a reflux condenser. The whole apparatus was efficiently flushed with oxygen gas and then connected to a balloon filled with oxygen. After vigorous stirring at 100 oC for 12 h, water was removed under vacuum and purified the reaction mixture by column chromatography (100-200 mesh silica gel, hexane-ethyl acetate) to obtain the product 4a as white solid. The other 1,3-oxazines were synthesized and purified by following the procedure described above
Green Chem., 2017, Advance Article DOI: 10.1039/C7GC02211E, Paper
F. A. Kucherov, K. I. Galkin, E. G. Gordeev, V. P. Ananikov
Efficient one-pot synthesis of tricyclic compounds from biobased 5-hydroxymethylfurfural (HMF) is described using a [4 + 2] cycloaddition reaction.
Efficient route for the construction of polycyclic systems from bioderived HMF
aZelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky pr. 47, Moscow 119991, Russia E-mail:val@ioc.ac.ru Web: http://AnanikovLab.ru
Abstract
The first synthesis of tricyclic compounds from biobased 5-hydroxymethylfurfural (HMF) is described. The Diels–Alder reaction was used to implement the transition from HMF to a non-planar framework, which possessed structural cores of naturally occurring biologically active compounds and building blocks of advanced materials. A one-pot, three-step sustainable synthesis in water was developed starting directly from HMF. The reduction of HMF led to 2,5-bis(hydroxymethyl)furan (BHMF), which could be readily involved in the Diels–Alder cycloaddition reaction with HMF-derived maleimide, followed by hydrogenation of the double bond. The described transformation was diastereoselective and proceeded with a good overall yield. The applicability of the chosen approach for the synthesis of analogous structures containing amine functionality on the side chain was demonstrated. To produce the target compounds, only platform chemicals were used with carbohydrate biomass as the single carbon source.
spectroscopy, SYNTHESISComments Off on Metal-free oxidative cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen
Green Chem., 2017, Advance Article DOI: 10.1039/C7GC02014G, Communication
Yanjun Xie, Xiangui Chen, Zhen Wang, Huawen Huang, Bing Yi, Guo-Jun Deng
Aerobic cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen under metal-free conditions.
Metal-free oxidative cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen
aKey Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China E-mail:hwhuang@xtu.edu.cn, gjdeng@xtu.edu.cn Fax: (+86)0731-5829-2251 Tel: (+86)0731-5829-8601
bCollege of Chemistry and Chemical Engineering, Hunan Institute of Engineering, Xiangtan 411104, China E-mail:bingyi2004@126.com
Metal-free oxidative cyclization for the one-pot synthesis of benzo[d]imidazo[2,1-b]thiazoles from 2-aminobenzothiazoles and cyclic ketones is described. Elemental sulfur combined with molecular oxygen as the benign co-oxidant was found to be unique and highly effective to promote this transformation without the aid of any metal salts. Various cyclic ketones smoothly reacted with 2-aminobenzothiazoles to give functional benzo[d]imidazo[2,1-b]thiazoles in good to very high yields, which thereby demonstrated the synthetic convergence of this methodology.
spectroscopy, SYNTHESIS, UncategorizedComments Off on Route to Benzimidazol-2-ones via Decarbonylative Ring Contraction of Quinoxalinediones: Application to the Synthesis of Flibanserin, A Drug for Treating Hypoactive Sexual Desire Disorder in Women and Marine Natural Product Hunanamycin Analogue
Route to Benzimidazol-2-ones via Decarbonylative Ring Contraction of Quinoxalinediones: Application to the Synthesis of Flibanserin, A Drug for Treating Hypoactive Sexual Desire Disorder in Women and Marine Natural Product Hunanamycin Analogue
ACS AuthorChoice – This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
INTRODUCTION
Benzimidazol-2-ones 1 are an important class of heterocycles and a privileged scaffold in medicinal chemistry. They consist of cyclic urea fused with the aromatic backbone, which can potentially interact in a biological system by various noncovalent interactions such as hydrogen bonding and π stacking. Benzimidazolone derivatives exhibit a wide range of biological activities, and they are useful in treating various diseases including cancer, type II diabetes, central nervous system disorders, pain management, and infectious disease.1 Selected compounds embedded with a benzimidazol-2-one moiety along with their use are captured in Figure 1. It is worth mentioning that oxatomide drug with a benzimidazol-2-one core was approved for marketing a few years ago.2a Very recently, US Food and Drug Administration approved a new drug called flibanserin for the treatment of hypoactive sexual desire disorder (HSDD) in females, which contains benzimidazol-2- one motif.2b
CONCLUSIONS
We have developed a mild and new protocol for the synthesis of benzimidazol-2-ones from quinoxalinediones through decarbonylation. The present methodology can be an addition to the toolbox to prepare benzimidazolones, and it will be useful in medicinal chemistry, particularly, late-stage functionalization of natural products, drug scaffolds, or an intermediate containing quinoxaline-2,3-diones. As direct application of this method, we have successfully developed a new route for the synthesis of recently approved drug flibanserin and a urea analogue of antibiotic natural product hunanamycin A. Later application demonstrates the utility of the present method in late-stage functionalization
Synthesis of 1-(2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethyl)-1,3-dihydro-2Hbenzo[d]imidazol-2-one (Flibanserin)
HRMS (ESI): m/z calculated for C20H22ON4F3[M+H]+ 391.1740 found 391.1743;
Scheme 4. Synthesis of Flibanserin through Ring Contraction
The same methodology was applied for the synthesis of flibanserin, also known as “female viagra”, which is the first approved medication for treating HSDD in women and is classified as a multifunctional serotonin agonist antagonist.(14, 15) Our synthesis of flibanserin commenced with 1-benzyl-1,4-dihydroquinoxaline-2,3-dione 36,(16) which was reacted with known chloride 37(17) under the basic condition in DMF to give the desired product 38 in good yield. Compound 38 was subjected for the decarbonylative cyclization under the optimized condition to afford the product 39 in 59% yield. Finally, the benzyl group was deprotected using trifluoromethanesulfonic acid in toluene under microwave irradiation,(8b, 18) which gave flibanserin in excellent yield (Scheme 4). The final product was isolated as HCl salt, and all of the spectral data are in agreement with the published data.(15c)
Rahul D. Shingare completed his M.Sc (Chemistry) from Fergusson College, Pune in 2008. He worked as a research associate in Ranbaxy and Lupin New drug discovery center, Gurgaon and Pune respectively until 2012 and currently pursuing his doctoral research in NCL – Pune from 2012.
Current Research Interests:Antibacterial Natural Product Hunanamycin A: Total Synthesis, SAR and Related Chemistry.
Akshay Kulkarni completed his M.Sc. from Ferguson College, Pune University in the year 2015 and joined our group as a Project Assistant in the month of October, 2015.
Current research interest: Synthesis of silicon incorporated biologically active antimalerial compounds.
e-mail : as.kulkarni@ncl.res.in
Dr.D. Srinivasa Reddy
Organic Chemistry Division
CSIR-National Chemical Laboratory
Stahl, S. M.Mechanism of action of Flibanserin, A multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorderCNS Spectrums2015, 20, 1 DOI: 10.1017/s1092852914000832
Ecocatalyzed Suzuki cross coupling of heteroaryl compounds
Green Chem., 2017, Advance Article DOI: 10.1039/C7GC01672G, Paper
Guillaume Clave, Franck Pelissier, Stephane Campidelli, Claude Grison
A bio-based EcoPd was developed for the Suzuki cross coupling of heteroaryl compounds.
Ecocatalyzed Suzuki cross coupling of heteroaryl compounds
aBio-inspired Chemistry and Ecological Innovations (ChimEco) UMR 5021 CNRS-University of Montpellier, Cap Delta, 1682 rue de la Valsière, 34790 Grabels, France E-mail:claude.grison@cnrs.fr
bLICSEN, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay 91191 Gif-sur-Yvette Cedex, France
Abstract
A bio-based EcoPd was developed for the Suzuki cross coupling of heteroaryl compounds. Based on the ability of Eichhornia crassipes to bioconcentrate Pd in its roots, we addressed the transformation of plant-derived Pd metals to green catalysts. The methodology is based on eco-friendly procedures. It allowed the preparation of a wide range of heterocyclic biaryl and heterocyclic–heterocyclic biaryl compounds, with a low Pd catalyst loading. EcoPd was found to have the ideal microstructure to promote complex Suzuki reactions without ligands or additives. For the first time, post-reaction solution was treated by rhizofiltration. The resulting EcoPd has been reused with the same performance. This work has established the ecocatalysis concept as a powerful strategy for Pd sustainability, with the development of homogeneous catalysts that are easily recycled and reused.
2-Bromothiophene (20 g, 125 mmol), Phenyl boronic acid (16.8 g, 138 mmol), potassium carbonate (20.7 g, 150 mmol) and EcoPd1 (113 mg, 125 µmol of Pd, 13.3 mg of Pd, EcoPd1 at 11.7 wt% of Pd) were suspended into degassed glycerol (200 mL). The mixture was stirred at 120°C for 4h thanks to an oil bath under an argon atmosphere. The reaction was checked for completion by TLC (cyclohexane) and GCMS analysis after a short extraction of the organic material: 10 µL of the crude were added into a 1 mL microtube containing a mixture of water and AcOEt (800 µL, 1:1, v/v) ; the microtube was vortexed before using the organic layer to perform analysis. Deionised water (500 mL) and AcOEt (500 mL) were added into the flask and the mixture filtered through fritted glass to isolate black Pd for recycling. The organic layer was further washed by deionised water (500 mL x 3) before drying over Na2SO4. The organic layer was filtered and concentrated under vacuum. The residue was then purified by chromatography on a silica gel column (250 g) with pure cyclohexane as the mobile phase, giving the desired coupled compound as a white powder (18 g, 112.5 mmol, yield 90%) Rf = 0.7 (cyclohexane).
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:rof2@lehigh.edu
Abstract
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.
cancer, new drugs, spectroscopy, SYNTHESISComments Off on Dr. Vinayak Pagar( GUEST BLOGGER) Development of a Povarov Reaction/Carbene Generation Sequence for Alkenyldiazocarbonyl Compounds
Metal-catalyzed cycloadditions of alkenyldiazo reagents are useful tools to access carbo- and heterocycles.[1] 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.[8]
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)
E-mail: rsliu@mx.nthu.edu.tw
Abstract
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.
[1] 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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] 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.
[8] 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).
spectroscopy, SYNTHESISComments Off on Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile
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.
aRWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, D-52074 Aachen, Germany E-mail:rene.koenigs@rwth-aachen.de
Abstract
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
The Departments of Pharmaceutical Sciences and Pharmaceutical Technology and Development, AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire SK10 2NA, United Kingdom
Examples of biologically active molecules containing a sulfoxide or sulfoximine: esomeprazole (3), aprikalim (4), oxisurane (5), OPC-29030 (6), ZD3638 (7), buthionine sulfoximine (8), and AZD6738 (9).
“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent
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