DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Worlddrugtracker, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his PhD from ICT ,1991, Mumbai, India, in Organic chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA as ADVISOR earlier GLENMARK LS Research centre as consultant,Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Prior to joining Glenmark, he worked with major multinationals like Hoechst Marion Roussel, now sSanofi, Searle India ltd, now Rpg lifesciences, etc. he is now helping millions, has million hits on google on all organic chemistry websites. His New Drug Approvals, Green Chemistry International, Eurekamoments in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 year tenure, good knowledge of IPM, GMP, Regulatory aspects, he has several international drug patents published worldwide . He gas good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, polymorphism etc He suffered a paralytic stroke in dec 2007 and is bound to a wheelchair, this seems to have injected feul in him to help chemists around the world, he is more active than before and is pushing boundaries, he has one lakh connections on all networking sites, He makes himself available to all, contact him on +91 9323115463, [email protected]

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: [email protected]

^bKey Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China
E-mail: [email protected]

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

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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: [email protected]

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: [email protected], [email protected]
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

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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: [email protected]
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

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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: [email protected], [email protected]
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: [email protected]

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-

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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: [email protected]. 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 : [email protected]

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]

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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]

[email protected]

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

Lifetime achievement award, WHC17, in Hyderabad, Telangana, India 22 Aug 2017

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Aug 252017

Speaking at World health congress 2017….JNTUH Hyderabad 22 aug 2017

Recent progress on fluorination in aqueous media

Uncategorized Comments Off

Jul 312017

Recent progress on fluorination in aqueous media

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01566F, Tutorial Review

Lian Yang, Tao Dong, Hrishikesh M. Revankar, Cheng-Pan Zhang
Advances of fluorination in aqueous media during the last few decades are summarized in this review

Recent progress on fluorination in aqueous media

Lian Yang,^a Tao Dong,^a Hrishikesh M. Revankar^a and Cheng-Pan Zhang*^a

*Corresponding authors

^aSchool of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, China
E-mail: [email protected], [email protected]

Abstract

Advances in aqueous fluorination during the last few decades are summarized in this review. Fluorinated compounds have dominated a large percentage of agrochemicals and pharmaceuticals and a mass of functional materials. The incorporation of fluorine atoms into organic molecules has become one of the mainstream technologies for their functional modification. Water is very environmentally friendly and has advantageous physicochemical properties. Fluorination reactions in aqueous media are highly sought-after, and have attracted great attention in research areas ranging from medicinal chemistry to materials science. In early times and for a long time, fluorination was thought to be diametrically opposed to water or moisture. However, recent examples have conflicted with this viewpoint. The successful merger of “untamed” fluorine and “mild” water in chemical reactions has set up a new prospect for green chemistry. A considerable amount of remarkable research works have been carried out using water as a (co)solvent and/or a reactant for transformations including electrophilic, radical, or nucleophilic fluorination. We hope that this review will serve as a guide to better understand and to further broaden the field of fluorine chemistry in aqueous conditions.

Conclusion

The installation of fluorine atoms into organic and organometallic frameworks can dramatically change their physical, chemical, and biological properties. Organofluorides have entered many fields of science and technology with a tremendous impact on these domains. The development of efficient, selective, and mild methods to build C-F bonds is of great importance, which is highly desirable to keep up with the rapidly growing demand of novel fluorine-containing scaffolds. In early times, most fluorination reactions required harsh conditions and moisture-sensitive, highly toxic, and explosive atomic fluorine transfer agents like fluorine gas, xenon difluoride, hypofluorite, antimonytrifluoride, and diethylaminosulfurtrifluoride. The discovery of stable electrophilic fluorination reagents such as Selectflour and NFSI has remarkably changed the dilemma, which realized a large number of safe, mild, and easily controllable electrophilic and radical fluorination reactions in aqueous media. Although the exact mechanisms are still unclear at present, it does never hamper the green fluorination method development with these reagents. A mass of successful examples have confirmed that the aqueous reaction medias have positive impacts on electrophilic and radical fluorination reactions with using the N-F reagents and in many cases water can also be a nucleophile for the entire conversions.

In addition, water was generally thought to be an unsuitable medium for nucleophilic fluorination because the fluoride ions can be “trapped” in aqueous medias by hydrogen bonding and become unreactive. Thus, their use in organic synthesis has been quite limited to polar aprotic solvents. Although the strong hydrogen bond formed between fluoride and water diminished the nucleophilicity of fluoride ions, the recent examples of nucleophilic fluorination in aqueous media have implied that this “negative” effect does not always harm the reaction. Besides, the radioisotope 18F has been considered to be a good choice for PET imaging owing to its desirable radiochemical properties. With a half-life of 110 minutes, the introduction of [ 18F]fluorine atoms into biomolecules has to be completed in a swift manner to minimize the loss of radioactivity. Nucleophilic incorporation of [18F]F‒ in aqueous conditions could rapidly produce [18F]fluorinesubstituted biomolecules, which avoided azeotropic drying process, shortened the production time, and minimized the loss of activity. We summarized the recent aqueous fluorination reactions in three sections according to their possible mechanisms. The successful amalgamation of “ill-tempered” fluorine and “benign” water has boded well for green fluorine chemistry. Water behaves as a cosolvent to dissolve fluorination reagents and/or as a reactant for bifunctionalization. Since the aspects of green chemistry has drawn much attention from the society, the pursuit of more efficient and milder reaction conditions for greener fluorination in aqueous medias will never end. Although a large number of research works have been published in this area, it’s only the tip of the iceberg with a wide scope for improvement. We hope that this review will serve as a guide to understand and to further broaden the field of aqueous fluorine chemistry. To meet the principle of green chemistry in modern synthesis, the development of new fluorination reagents as well as valid catalytic systems is crucial for mild and selective C-F bond formation. It’s undoubted that a growing number of green fluorination methodologies in aqueous media will be witnessed in the near future.

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