Sustainable chemistry: how to produce better and more from less?

Uncategorized Comments Off

Oct 072017

Sustainable chemistry: how to produce better and more from less?

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02006F, Perspective

P. Marion, B. Bernela, A. Piccirilli, B. Estrine, N. Patouillard, J. Guilbot, F. Jerome
This review describes the rapid evolution of chemistry in the context of a sustainable development of our society. Written in collaboration between scientists from different horizons, either from public organizations or chemical companies, we aim here at providing recommendations to accelerate the emergence of eco-designed products on the market.

Sustainable chemistry: how to produce better and more from less?

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02006F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

P. Marion,^a B. Bernela,^b A. Piccirilli,^c B. Estrine,^d N. Patouillard,^e J. Guilbot^f and F. Jérôme*^g

Author affiliations

*Corresponding authors

^aSOLVAY, 85 rue des frères Perret, BP 62, F-69192 Saint Fons Cedex, France

^bINCREASE FR CNRS 3707/Centre de Recherche sur l’Intégration Economique et Financière, Université de Poitiers, 2 rue Jean Carbonnier, Bât A1, 86073 Poitiers Cedex 9, France

^cBIOSYNTHIS, 6 Chemin de la Pierre Percée, 91410 Saint-Cyr-sous-Dourdan, France

^dARD-Agro-industrie Recherches et Développements, Green Chemistry Department, Route de Bazancourt, F-51110 Pomacle, France

^ePENNAKEM LLC, 3324 Chelsea avenue, Memphis, USA

^fSEPPIC-AIR LIQUIDE, 127 chemin Poudrerie, 81105 Castres, France

^gINCREASE FR CNRS 3707/Institut de Chimie des Milieux et Matériaux de Poitiers, Université de Poitiers, ENSIP, 1 rue Marcel Doré, 86073 Poitiers, France
E-mail: francois.jerome@univ-poitiers.fr

Abstract

The International Symposium on Green Chemistry (ISGC) organized in 2013, 2015 and 2017 has gathered many senior and young talented scientists from all around the world (2200 attendees in three editions), either from academia or industry. Through outstanding conferences, communications, debates, and round tables, ISGC has been the witness of the rapid evolution of chemistry in the context of a sustainable development of our societies, not only at the scientific and industrial levels but also on education, networking and societal aspects. This critical review synthesizes the different points of view and the discussions having taken place at ISGC and gives a general picture of chemistry, including few scientific disciplines such as catalysis, processes, resource management, and environmental impact, among others, within the framework of sustainable development. This critical review, co-authored by researchers from public organizations and chemical companies (small, medium and large industrial groups) provides criteria and recommendations which, in our view, should be considered from the outset of research to accelerate the emergence of eco-designed products on the market.

Conclusions

Sustainable chemistry is the only mean to generate performant products and long lasting solutions able to generate business and profit for chemical industry. Performance is the best systemic answer for customer needs and our societies. Defining sustainable chemistry is, however, far to be an easy task because chemistry is a highly dynamic system. The sustainability of a value chain is for instance directly depending on the access to energy (and above all to its origin – coal, gas, biomass…) and on the supply of raw materials. In the current economic context, it could be not so easy to predict what will be the best source of energy or raw materials for a desired product in the future. The development of predictive tools is now essential and will represent probably one of the next scientific challenges in the coming years. During the last 20 years, utilization of renewable feedstocks in chemical processes has become a strategy of growing interest but it definitely does not guarantee the establishment of a sustainable chemistry. Indeed, in some cases, it is more sustainable to produce a chemical from a fossil carbon source using decarbonized energy than the reverse. It is very important to distinguish the carbon found in the final product from the carbon content corresponding to the energy which is required the product production (going from raw materials to manufacturing, end of life, etc.). In this area, the concept of biorefinery can help to secure developments and to minimize investments in production plant by mutualizing facilities and R&D initiatives. Cooperation with local producers can also be a valuable way to implement new bio‐based products while favouring sustainable agricultural practices. Whatever the raw materials (renewable or fossil), a complete and systemic life cycle analysis of the whole chain value (from resources to manufacturing, use and end of life) must be performed because it gives us an accurate picture of the overall economic, environmental and societal performances of a product in an application for a defined market. In general, one should never forget that sustainable chemistry should help the society to produce more and better (products). Emergence of sustainable innovations on the market takes a lot of time because chemists have to reinvent chemistry. To achieve our transition to a sustainable society, we must think differently and bring together the worlds of finance, manufacturers, researchers and public authorities. The current method of funding of research and innovation is not satisfying yet because too often based on short‐term projects and with high Technology Readiness Level. Governments have to realize that this funding method slows down, and sometime also hampers, the emergence of future sustainable innovations. Evolution of regulations with the aim of banning toxic, eco‐toxic or poor biodegradable products is an important driver for sustainable innovation. It is now seen and shared as a positive sign providing opportunities to develop systemically better solutions and allowing chemical companies advocating sustainable development and products as a must to stay in the competition. As examples, ban of CFC, replacement of chlorinated or other toxic solvents, substitution of endocrine disruptors lead to better solutions for the global benefit of our societies. Improving public perception and awareness on sustainable chemistry is on the way but more efforts will be needed in the future to definitely contribute to the emergence of eco‐ designed chemicals on the market.

/////////

Below we provide a bulleted list to summarize the main recommendations that are, in our views, essential for designing sustainable products. (1) Products design & Manufacture: For the intended application, sustainable chemicals must imperatively bring a global benefit, created by a scientific or technological breakthrough, while minimizing risks. They should also generate profit to emerge on the market. Products should be produced according to the 12 principles of green chemistry. In addition, their end of life should be integrated at the outset of research, (2) Resources: They should be available for future generations and should have low environmental impact (protecting endangered species, deforestation, erosion of biodiversity, contamination of natural resources, global warming, etc.), it should make progress the societal development of concerned area (sharing any benefits with local producer, no child labour, help developing countries, etc.) and their utilization should not destabilise other supply chains. Non edible raw material, a return to the idea of ‘localness’ and the need for closeness should be preferred, (3) Process: The ideal process would be a low Capex or a progressive Capex process and should be energy‐efficient, not use solvents, be without effluents, should limit the number of reactional and purification steps and should be developed rapidly to limit the associated risks and costs. Efforts are still needed for miniaturisation of equipment, intensification and development of continuous reactors, (4) Energy: The chemical industry is also energy intensive. Although less than 10% of fossil carbon is used for the manufacture of chemicals, finding decarbonized sources of energy is mandatory to avoid the depletion of carbon reserves and price increase and to ensure that future generations will have access to the same resource in the same amount, (5) Life cycle assessment: it should be assessed in all cases, the earlier the better, by preferring a ‘cradle to grave’ approach. It should give an accurate picture of the overall economic, environmental and societal performances of a product in an application for a defined market, (6) Education: we should improve public awareness and perception on sustainable chemistry to facilitate the acceptation of sustainable products by the consumer. More education programs should be launched in the future not only to reassure the consumer but also to create a pool of students better armed to tackle the future challenges of (sustainable) chemistry. The rapid development of digital tools should be helpful to address this issue, (7) Network: we should prefer working in an open innovation mode by bringing together the worlds of finance, manufacturers, researchers and public authorities to accelerate the emergence of eco‐designed chemicals on the market. Networks should enable local players to adapt to changes in their environment while optimising their economic and environmental efficiency, (8) Funding: A good balance between funding to applied research and basic research must be addressed in order to continuously generate scientific innovation. However, public authorities must realise that societal challenges are more important than the short term financial challenges faced by businesses. The current model of our economy based on rapid profitability is unfortunately not well adapted for these advances since long‐term investments will be needed for a more sustainable development of our society, (9) Legislation & Regulation: it should facilitate the emergence of sustainable chemicals by banning harmful chemicals for the human health and the environment, even those nowadays generating substantial profits. The registration process of improved sustainable chemicals by the concerned agencies should be quicker than now to speed up their integrations on the market, (10) Predictive methods: the development of tools to accurately predict the technical and application performances, the economic efficiency, the environmental and societal performance of a targeted product should be developed to limit the risks and costs associated with potential failure and to reassure the investors. It is also urgent to develop these tools for chemicals that are intended to be dispersed in nature.

Total synthesis of natural products viairidium catalysis

SYNTHESIS Comments Off

Sep 292017

Total synthesis of natural products via iridium catalysis

Org. Chem. Front., 2017, Advance Article
DOI: 10.1039/C7QO00664K, Review Article

Changchun Yuan, Bo Liu
An overview of the highlights in total synthesis of natural products using iridium as a catalyst is given

http://pubs.rsc.org/en/Content/ArticleLanding/2017/QO/C7QO00664K#!divAbstract

Total synthesis of natural products viairidium catalysis

Changchun Yuan*^a and Bo Liu*^b

Author affiliations

*Corresponding authors

^aSchool of Chemical Engineering and Technology, North University of China, Taiyuan 030051, PR China
E-mail: ycc543700483@nuc.edu.cn

^bKey Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China
E-mail: chembliu@scu.edu.cn

Abstract

Catalysis with transition metals is a powerful synthetic tool for achieving a high degree of molecular complexity from relatively simple building blocks. Among these transition metals employed, iridium has attracted significant attention owing to its multifold roles in catalysis of various synthetically significant methodologies, and thus iridium catalysts are widely used in natural product synthesis. This review aims to comprehensively summarize recent accomplishments in total synthesis of natural products using iridium as the catalyst.

Image result for School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, PR China

School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, PR China

Image result for College of Chemistry, Sichuan University, Chengdu

Image result for College of Chemistry, Sichuan University, Chengdu Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu

///////////

Photochemical intramolecular amination for the synthesis of heterocycles

FLOW CHEMISTRY, flow synthesis Comments Off

Sep 272017

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02261A, Communication

Shawn Parisien-Collette, Corentin Cruche, Xavier Abel-Snape, Shawn K. Collins
Polycyclic heterocycles can be formed in good to excellent yields via photochemical conversion of the corresponding substituted aryl azides under irradiation with purple LEDs in a continuous flow reactor.

Photochemical intramolecular amination for the synthesis of heterocycles

Shawn Parisien-Collette,^a Corentin Cruché,^a Xavier Abel-Snape^a and Shawn K. Collins*^a

Author affiliations

*Corresponding authors

^aShawn Parisien-Collette, Corentin Cruché, Xavier Abel-Snape and Prof, Dr Shawn K. Collins, Department of Chemistry and Centre in Green Chemistry and Catalysis, Université de Montréal, CP 6128 Station Downtown, Montréal, Canada H3C 3J7
E-mail: shawn.collins@umontreal.ca

Abstract

Polycyclic heterocycles can be formed in good to excellent yields via photochemical conversion of the corresponding substituted aryl azides under irradiation with purple LEDs in a continuous flow reactor. The experimental set-up is tolerant to UV-sensitive functional groups while affording diverse carbazoles, as well as an indole and pyrrole framework, in short reaction times. The photochemical method is presumed to progress through a mechanism differing from the other methods of azide activation involving transition metal catalysis.

Methyl 9H-carbazole-2-carboxylate (9): Following the Photodecomposition Procedure A, starting from Methyl 2’-azido-[1,1’-biphenyl]-4-carboxylate, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a white solid (24.3 mg, 72 % yield). Following the Photodecomposition Procedure B, starting from Methyl 2’-azido-[1,1’- biphenyl]-4-carboxylate, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a white solid (27.7 mg, 82 % yield). NMR data was in accordance with what was previously reported.16

16 Takamatsu, K.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2014, 16, 2892-2895

NEXT…………..

4-Isopropyl-9H-carbazole (14): Following the Photodecomposition Procedure A, starting from 2-azido-2’-isopropyl-1,1’-biphenyl, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a yellow solid (16.6 mg, 53 % yield). Following the Photodecomposition Procedure B, starting from 2-azido-2’-isopropyl-1,1’-biphenyl and using ethyl acetate as the solvant, the crude mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a yellow solid (16.0 mg, 51 % yield).

1H NMR (400 MHz, DMSO-d6) δ = 11.29 (s, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.39-7.31 (m, 3H), 7.19- 7.15 (m, 1H), 7.08-7.03 (m, 1H), 3.92-3.82 (m, 1H), 1.41 (d, J = 6.8 Hz, 6H);

13C NMR (100 MHz, DMSO-d6) δ = 143.9, 140.3, 140.1, 126.0, 125.2, 122.8, 122.2, 119.9, 119.1, 114.9, 111.2, 108.9, 30.2, 22.8 (2C);

HRMS (ESI) m/z calculated for C15H15N [M-H]- 208.1130; found 208.1126.

///////////http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02261A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Catalyst-free multi-component cascade C-H-functionalization in water using molecular oxygen: an approach to 1,3-oxazines

spectroscopy, SYNTHESIS Comments Off

Sep 202017

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

Mohit L. Deb,*^a Choitanya D. Pegu,^a Paran J. Borpatra,^a Prakash J. Saikia^b and Pranjal K. Baruah*^a

Author affiliations

*Corresponding authors

^aDepartment of Applied Sciences, GUIST, Gauhati University, Guwahati-781014, India
E-mail: mohitdd.deb@gmail.com, baruah.pranjal@gmail.com
Fax: +91-8876998905
Tel: +91-8876998905

^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.

15-phenyl-7a,12,13,15-tetrahydronaphtho[1′,2′:5,6][1,3]oxazino[2,3- a]isoquinoline (4a):1

White solid; Yield 61 %, 221 mg;

1H NMR (500 MHz, CDCl3): δ 7.79-7.77 (m, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.43-7.41 (m, 1H), 7.33-7.28 (m, 8H), 7.24-7.19 (m, 3H), 7.11 (d, J = 8.9 Hz, 1H), 5.65 (s, 1H), 5.44 (s, 1H), 3.40-3.26 (m, 2H), 3.12-3.09 (m, 1H), 2.90- 2.86 (m, 1H);

13C NMR (125 MHz, CDCl3): δ 151.9, 142.3, 135.0, 133.0, 132.4, 129.3, 129.1, 128.9, 128.8 (2C), 128.7, 128.6, 128.2, 127.4, 126.5, 126.2, 123.1, 122.7, 118.9, 110.9, 82.2, 62.6, 45.4, 29.4;

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

//////////////

Efficient route for the construction of polycyclic systems from bioderived HMF

spectroscopy, SYNTHESIS Comments Off

Sep 162017

Efficient route for the construction of polycyclic systems from bioderived HMF

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

F. A. Kucherov,^a K. I. Galkin,^a E. G. Gordeev^a and V. P. Ananikov*^a

Author affiliations

*Corresponding authors

^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.

Endo-4,7-bis(hydroxymethyl)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (endo-4,7-bis(hydroxymethyl)norcantharimid-5-ene), 3

1H NMR (DMSO-d6) = 10.82 (s, 1H), 6.37 (s, 2H), 5.11 (t, 2H, J = 5.7 Hz), 3.97 (dd, 2H, J = 5.7 Hz, 12.8 Hz), 3.84 (dd, 2H, J = 5.7 Hz, 12.8 Hz), 3.44 (s, 2H);

13C NMR (DMSO-d6) = 176.9, 136.0, 92.1, 59.8, 48.8 ppm.

m/z HRMS (ESI) Calcd. for C10H11NO5 [M+Na]: 248.0529. Found 248.0536.

STR7

1H NMR PREDICT

13C NMR PREDICT

//////////

O=C1NC(=O)[C@H]3[C@@H]1[C@]2(C=C[C@]3(CO)O2)CO

Padma Shri 2018 nomination on 10 sept 2018

award Comments Off

Sep 112017

Nominated for Padmashri…….

http://padmaawards.gov.in/card.aspx?NomineeUID=C6C4653CC138F977EC983A5FEA8F73D1F4B1576F9708D063B6AB1F605961B0C1&rand=106540

Metal-free oxidative cyclization of 2-aminobenzothiazoles and cyclic ketones enabled by the combination of elemental sulfur and oxygen

spectroscopy, SYNTHESIS Comments Off

Sep 072017

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

Yanjun Xie,^a^b Xiangui Chen,^a Zhen Wang,^a Huawen Huang,*^a Bing Yi*^b and Guo-Jun Deng*^a

*Corresponding authors

^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

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02014G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Abstract

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.

7,8,9,10-Tetrahydrobenzo[d]benzo[4,5]imidazo[2,1-b]thiazole (3a)

White solid; yield: 39.2 mg (86%), mp 140-142 °C.

1H NMR (400 MHz, CDCl3, ppm) δ 7.67-7.62 (m, 2H), 7.38 (t, J = 7.76 Hz, 1H), 7.27 (t, J = 7.68 Hz, 1H), 3.07-3.04 (m, 2H), 2.77-2.74 (m, 2H), 2.00-1.95 (m, 2H), 1.92-1.86 (m, 2H);

13C NMR (100 MHz, CDCl3, ppm) δ 145.1, 142.4, 132.9, 129.7, 125.5, 123.9, 123.5, 121.8, 111.9, 24.8, 22.8, 22.7, 21.8;

MS (EI) m/z (%) 228, 200 (100), 160, 108, 51;

HRMS calcd. for: C13H13N2S + (M+H)+ 229.07940, found 229.07941.

PREDICT

cas 325766-28-7

C₁₃ H₁₂ N₂ S, 228.31, Benzimidazo[2,1-b]benzothiazole, 7,8,9,10-tetrahydro-

///////////////

C1CCCc2c1nc3sc4ccccc4n23

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

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Sep 012017

Image result for ncl pune

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

Rahul D. Shingare^†^‡, Akshay S. Kulkarni^†, Revannath L. Sutar^†, and D. Srinivasa Reddy ^*^†^‡

^† Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India

^‡ Academy of Scientific and Innovative Research (AcSIR), New Delhi 110 025, India

ACS Omega, 2017, 2 (8), pp 5137–5141

DOI: 10.1021/acsomega.7b00819

http://pubs.acs.org/doi/abs/10.1021%2Facsomega.7b00819

*E-mail: ds.reddy@ncl.res.in. Phone: +91-20-2590 2445 (D.S.R.).

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)

Flibanserin hydrochloride as white solid.

1H NMR (400MHz ,DMSO-d6)  11.06 (s, 1 H), 10.93 (br. s., 1 H), 7.54 – 7.41 (t, J = 7.9 Hz, 1 H), 7.36 – 7.22 (m, 3 H), 7.15 (d, J = 7.6 Hz, 1 H), 7.09 – 7.01 (m, 3 H), 4.30 (t, J = 6.7 Hz, 2 H), 4.01 (d, J = 11.6 Hz, 2 H), 3.75 (d, J = 10.4 Hz, 2 H), 3.54 – 3.43 (d, J = 4.2 Hz 2 H), 3.31 – 3.10 (m, 4 H);

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)

Image result for Rahul D. Shingare

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.

e-mail: rd.shingare@ncl.res.in

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

Image result for Rahul D. Shingare

Dr.D. Srinivasa Reddy
Organic Chemistry Division
CSIR-National Chemical Laboratory

14.

Stahl, S. M. Mechanism of action of Flibanserin, A multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder CNS Spectrums 2015, 20, 1 DOI: 10.1017/s1092852914000832

[CrossRef], [PubMed], [CAS]
15.

See, previous synthesis of Flibanserin:

(a) Bietti, G.; Borsini, F.; Turconi, M.; Giraldo, E.; Bignotti, M. For treatment of central nervous system disorders. U.S. Patent 5,576,318, 1996.

(b) Mohan, R. D.; Reddy, P. K.;Reddy, B. V. Process for the preparation of Flibanserin involving novel intermediates. WO2010128516 A2,2010.

(c) Yang, F.; Wu, C.; Li, Z.; Tian, G.; Wu, J.; Zhu, F.; Zhang, J.; He, Y.; Shen, J. A Facile route of synthesis for making Flibanserin Org. Process Res. Dev. 2016, 20, 1576 DOI: 10.1021/acs.oprd.6b00108

[ACS Full Text ], [CAS]
16.

Jarrar, A. A.; Fataftah, Z. A. Photolysis of some quinoxaline-1,4-dioxides Tetrahedron 1977, 33, 2127 DOI: 10.1016/0040-4020(77)80326-8

[CrossRef], [CAS]
17.

Xueong, X. Preparation method of Flibanserin. CN104926734 A, 2015.
18.

Rombouts, F.; Franken, D.; Martínez-Lamenca, C.; Braeken, M.; Zavattaro, C.; Chen, J.; Trabanco, A. A.Microwave-assisted N-debenzylation of amides with triflic acid Tetrahedron Lett. 2010, 51, 4815 DOI: 10.1016/j.tetlet.2010.07.022

[CrossRef], [CAS]

//////////

ENHANCEMENT OF DISSOLUTION RATE AND SOLUBILITY OF LOSARTAN POTASSIUM BY USING SOLID DISPERSION METHOD β-CYCLODEXTRIN AS CARRIER

Uncategorized Comments Off

Aug 252017

ENHANCEMENT OF DISSOLUTION RATE AND SOLUBILITY OF LOSARTAN POTASSIUM BY USING SOLID DISPERSION METHOD β-CYCLODEXTRIN AS CARRIER

Dr. M. Sunitha Reddy*, CH.Soujanya, MD. Fazal ul Haq

[ABSTRACT] [PDF]

baddam_sunitha@rediffmail.com

file:///C:/Users/Inspiron/Downloads/article_wjpr_1448882058.pdf

ABSTRACT In the present study an attempt was made to increase the therapeutic effectiveness of losartan potassium,by increasing the solubility and dissolution rate via solid dispersion using β-cyclodextrin as carrier. Losartan potassium is an Antihypertensive agent but failed to show good therapeutic effect. Eight solid dispersion formulations of losartan potassium were prepared by using different drug:polymer ratios viz.1:2,1:2,1:3,1:4 by novel methods like Hot melt extrusion,Lyophilization.prepared solid dispersions were evaluated. The blend of all the formulations showed good flow properties such as angle of repose, bulk density, tapped density. All the solid dispersion formulations were compressed into orodispersible tablets with weight equivalent to losartan potassium of 25mg by direct compression method using 6mm punch on 8 station rotary tablet punching machine. The prepared tablets were evaluated for its hardness, disintegration, weight variation, friability and invitro dissolution studies.The Infra Red spectra revealed that there is no incompatability between the drug and excipients. The prepared tablets were shown good post compression parameters and they passed all the quality control evaluation parameters as per I.P limits. Among all the formulations F4 and F8 formulations showed maximum % drug release i.e.93.83%(Lyophilization), 97.10%(Hot melt extrusion method) within 45min.these are compared with pure drug which shows %drug release58.67%. The optimized formulations were subjected to different kinetic models.the formulations were found to follow zero order release. optimized formulations Were subjected to Accelerated stability study for 3 months according to ICH guidelines.The results found to satisfactory.

Considering all evaluation parameters and % drug release F8 formulation shown better % drug release compared with F4 formulation. hence F8 formulation considered as optimised formulation.

KEYWORDS: Losartan potassium, β-cyclodextrin, solid dispersion, Lyophilization, Hot melt extrusion. FTIR.

CONCLUSION Losartan potassium is belongs to class II drugs, that is, characterized by low solubility and low permeability therefore, the enhancement of its solubility and dissolution profile is expected to significantly improve its bioavailability and reduce its side effects. The precompression blends of Losartan were characterized with respect to angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. The precompression blend of all the batches indicates well to fair flowability and compressibility. Among all the formulations F8 formulation, showed good result that is 97.10 % in 45 minutes. As the concentration of polymer increases the drug release was decreased.

Anthony Melvin Crasto

Award given by Dr. M Sunitha Reddy Head of the Department, Centre for Pharmaceutical Sciences, Institute of Science &Technology, JNTU-H, Kukatpally, Hyderabad, India

Lifetime achievement award ……..WORLD HEALTH CONGRESS 2017 in Hyderabad, 22 aug 2017 at JNTUH KUKATPALLY. HYDERABAD, TELANGANA, INDIA, Award given by Dr. M Sunitha Reddy Head of the Department, Centre for Pharmaceutical Sciences, Institute of Science &Technology, JNTU-H, Kukatpally, Hyderabad, India