One Organic Chemist One Day............Honouring Profiles of leading Organic Chemists brought to you by DR ANTHONY MELVIN CRASTO, worlddrugtracker, helping millions, amcrasto@gmail.com, +91 9323115463, India, skype amcrasto64
DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution
Five chemists from Indonesia, Jamaica, Nigeria, Uzbekistan and Yemen have won at the second Elsevier Foundation Awards for Early Career Women Scientists in the Developing World. Indonesia, Ritmaleni from the Gadjah Mada University Simone Ann Marie Badal McCreath from the University of the West Indies, Jamaica. Taiwo Olayemi Elufioye from the University of Ibadan, Nigeria; Nilufar Mamadalieva from the Institute of the Chemistry of Plant Substances, Uzbekistan; Eqbal Mohammed Abdu Dauqan from the Al-Saeed University, Yemen;
Paul Murray Catalysis Consulting helps companies to save money and resources through more efficient chemical processes.
About
Dr Paul Murray is a world leading consultant scientist, providing expertise and training in the fields of Catalysis, Design of Experiments and Principal Component Analysis. Paul is an experienced scientist with an additional expertise in automation, multivariate data analysis, process development and problem solving. Paul has a proven track record of the timely delivery of innovative solutions to client projects resulting in significant reductions in costs and resources to customers.
Paul Murray Catalysis Consulting provides expertise in:
The development and optimisation of challenging catalytic reactions.
The use of Principal Component Analysis (PCA) to optimise ligand and solvent selection.
The use of advanced experimental design linking DoE with PCA for efficient reaction development.
The development and use of automation for reaction screening including catalyst screening.
The development of chemical reactions across all stages from identification and exploitation of new chemical reaction selectivity’s through to commercial manufacture.
Paul Murray Catalysis Consulting offers consultancy in all aspects of Catalysis, Design of Experiments, Principal Component Analysis, solvent selection and process development.
Design of Experiments to efficiently identify important reaction parameters and optimise processes:
Selection of the appropriate designs, factors and ranges for an experimental investigation.
The analysis and interpretation of the experimental data.
The prediction of reaction outcomes from the Design of Experiments model.
Principal Component Analysis to rationalise diverse sets of materials such as solvents:
Selection of suitable properties for chemical datasets to generate appropriate PCA maps.
Selection of materials from PCA maps to enable the efficient understanding of the chemical space and requirements of the chemical reaction.
Selection of the appropriate designs and analysis of experimental data.
Partial Least Squares (PLS) modelling to understand the properties of materials that play a significant role in optimum reaction development and prediction of suitability of additional materials for the chosen reaction.
Catalysis:
Homogeneous, heterogeneous and bio catalysis
Recommendation of reaction conditions for an array of transformations.
Guide experimental programs to optimise processes including the selection of the optimum catalyst and ligand.
Detailed analysis of reaction outcomes to diagnose the source of the trouble.
Optimisation of a commercial manufacturing process to make a sustainable and economically viable long term process.
Design of new shorter synthetic routes that fully exploit the opportunities presented by catalysis.
Summary
Consultant with expertise in;
- the development and optimisation of challenging chemical reactions.
- applied homogeneous and heterogeneous catalysis.
- the use of advanced experimental design linking DoE with PCA for efficient reaction development.
- the use of Principal Component Analysis (PCA) to optimise ligand and solvent selection.
- the development and use of automation for reaction screening including catalyst screening.
- the development of chemical reactions across all stages from identification and exploitation of new chemical reaction selectivity’s through to commercial manufacture.
- process development.
- development of short sustainable synthetic routes.
- rapid evaluation of new chemistry.
- problem solving.
A leading pharma company needed to manufacture 100kg of an API using a Suzuki reaction. The catalyst for this process would have cost $500k. We identified alternative catalyst systems which reduced the catalyst cost of this process by more than $400k.
– Present (1 year 4 months)Bristol, United Kingdom
Paul Murray Catalysis Consulting enables clients to save money and resources by developing efficient cost effective chemical processes through the use of advanced Design of Experiments.
Paul Murray Catalysis Consulting provides clients with expertise in the field of catalysis across all stages of development and manufacture. The company also offers training and consulting in the use of advanced Design of Experiments (DoE) and Principal Component Analysis (PCA).
Linking PCA with DoE enables the comparison of diverse chemicals such as solvents or ligands to each other and their efficient investigation within experimental design
I am responsible for the continuing development and improvement of PhosphonicS products and services, with a particular focus in precious metal recovery applications.
As a Visiting Industrial Fellow at the University of Bath, I will be collaborating with academics and providing training and support for students in their use of Design of Experiments and Principal Component Analysis.
CatScI is a UK based company with extensive knowledge and expertise in a wide range of chemistry R&D activities at all stages of the project timeline, from discovery chemistry through to full scale manufacturing and life-cycle management.
CSO providing expertise in catalysis, automation, design of experiments, multivariate analysis, while continuing to expand the CatScI catalysis capability.
I started working as a process chemist in AstraZeneca in September 1998. I spent 2 years working on early stage chemistry (scale up of medicinal chemistry processes) before going on to look at later stage development and some life cycle management. I then spent a year working on our Pilot Manufacturing facility at Loughborough from mid 2001 before returning to Process Chemistry. In 2003 I became involved in the AstraZeneca Catalysis Group where I designed and set up our first dedicated catalyst screening facility. This facility now provides a service to AstraZeneca Process R&D globally as well as supporting Discovery chemistry.
DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro-drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, r is 0 or 1 and X1 is linear (1-3C)alkyl; q is 0 or 1 and X1 is fluoro, chloro or (1-3C)alkyl; Y1 is selected from fluoro, chloro, bromo, cyano, (1...more
A dibenzothiazepine compound is suitably prepared by subjecting a 2-amino-2′-carboxy-diphenylsulfide compound to dehydration-condensation reaction in the presence of an acidic catalyst; the 2-amino-2′-carboxy-diphenylsulfide compound is suitably prepared by reducing a 2-nitro-2′-carboxy-diphenylsulfide compound in a lower aliphatic ester solvent; and the 2-nitro-2′-carboxy-diphenylsulfide compound...more
A process for the manufacture of a compound of formula (V), useful for making rosuvastatin, by a stereoselective aldol reaction is described. Novel intermediates and processes to make them are also described.
A process for preparing a compound of formula (I) where R4 and R5 are as defined in the specification; and R6 is hydrogen or a protecting group, which process comprises cyclisation of a compound of formula (II) where R4, R5and R6 are as defined in relation to formula (I) and R7is a nitrogen-protecting group, and removing protecting group R7-, and thereafter if desired or necessary, removing any...more
The invention relates to a process for prepn. of rosuvastatin [I; R = (E)-(3R,5S)-3,5-dihydroxyhept-6-enoic acid residue, R1 = MeSO2NMe] involving reaction of I (R is a leaving group, R1 is MeSO2NMe or a precursor) with a protected 3,5-dihydroxyhept-6-enoic acid deriv. or related compd. Thus, treatment of N-[5-bromo-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-...more
Preparation of pyrimidine derivatives and guanine derivatives, and their use in treating tumor cells
United States US 6096724
Issued August 1, 2000
The present invention provides certain 6-hetarylalkyloxy pyrimidine derivs. I [R is a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hetero atom chosen from O, N, or S, or a substituted deriv. thereof, or an (un)substituted Ph; R2 = H, C1-5-alkyl, halogen...more
The present invention provides certain 6-hetarylalkyloxy pyrimidine derivatives of formula II ##STR1## wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hetero atom chosen from O, N, or S, or a substituted derivative thereof; or (ii) phenyl or a...more
The invention provides compounds exhibiting the ability to deplete O6-alkylguanine-DNA alkyltransferase (ATase) activity in tumour cells. The compounds include certain pyrimidine derivatives of formula (II), wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having...more
Courses
Independent Coursework
Chemical Development & Scale-Up in the Fine Chemical & Pharmaceutical Industries, Scientific Update
Design of Experiments, Umetrics
Multivariate Data Analysis, Umetrics
Synthesis and Methods, Scientific Update
Reaction Progress Kinetics, Donna Blackmond
Business Link Business Start-up
Catalytic Cross Coupling Reactiosn in Aromatic and Heteroaromatic Synthesis
My PhD was carried out under the supervision of Professor T Brian H McMurry on “The synthesis of selected heterocyclic compounds as potential inhibitors of O6-alkylguanine-DNA-alkyltransferase (ATase)”
Journal of Chemical Technology and Biotechnology, 2014, 89 (5), 623-632
February 13, 2014
Transition metal-catalyzed reactions are often strongly dependent on ligand and selection, among other factors, which makes discovering the ideal metal/ligand/solvent combination demanding. Furthermore, the effect of ligand and solvent choice is often subtle and unpredictable. This perspective describes how two statistical techniques, design of expts. (DoE) and principal component anal. (PCA),...more
Organic Process Research & Development, 2013, 17 (3), 397–405
January 17, 2013
The Heck–Mizoroki (HM) reaction is one of the most widely used C–C bond-forming methods of contemporary synthesis. Notwithstanding this, these reactions frequently require significant optimization before efficient transformations can be obtained. We describe here the results of a study that aimed to establish a generic experimental protocol for HM reactions which enables acceptable yields from...more
We present here an informed estimate of the millions of parameter settings that might be required to optimise one typical transition-metal-catalysed reaction. We describe briefly how both Design of Experiments (DoE) and Principal Component Analysis (PCA) techniques may be combined to reduce the number of potential reaction settings to a practical number of experiments without losing critical...more
We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor ligands (LKB-PP, Organometallics 2008, 27, 1372–1383) by 208 ligands and introduced an additional steric descriptor (nHe8). This expanded knowledge base now captures information on 334 bidentate ligands and has been processed with principal component analysis (PCA) of the descriptors to produce a detailed map of bidentate...more
A mild but robust procedure has been developed as a first pass generic protocol for the Suzuki–Miyaura reaction. The protocol employs an air stable palladium pre-catalyst at low loading (≤1 mol %) in aqueous solvent mixtures at moderate temperature using potassium carbonate as base. Under these mild conditions, most aryl bromides will react with sterically and electronically demanding aryl boronic...more
The concept and evolutionary development of a generic protocol to give a fit-for-purpose and/or proof of transformation for a common transition metal catalysed reaction is discussed. The case for such protocols as the basis for further development and optimisation of these challenging reactions is presented. The use of advanced statistical techniques (DoE/PCA) to ensure the efficient planning of...more
We have expanded the ligand knowledge base for monodentate P-donor ligands (LKB-P, Chem. Eur. J. 2006, 12, 291−302) by 287 ligands and added descriptors derived from computational results on a gold complex [AuClL]. This expansion to 348 ligands captures known ligand space for this class of monodentate two-electron donor ligands well, and we have used principal component analysis (PCA) of the...more
Angewandte Chemie, International Edition 2010 , 49, 5156 –5160
June 11, 2010
Undercover agents: The biaryl coupling of an aryltrifluoroborate with an aryl bromide involves in situ hydrolysis of the boron reagent. The hydrolysis products are key components in ensuring that the reaction proceeds with high efficiency and avoids the extensive generation of undesired phenolic and homocoupling side products.
Angewandte Chemie, International Edition 2009, 48(41), 7612-7615
September 10, 2009
The development of a catalyst for the Newman–Kwart rearrangement allows an escape from the harsh thermal conditions of the standard uncatalyzed reaction (see scheme). Mechanistic investigations, employing kinetic, isotopic labelling (2H, 18O, 34S) and DFT studies, suggest that the reaction proceeds through a five-centred Pd–S coordinated oxidative addition, with intermolecular exchange of aryl and...more
Org. Process Res. Dev., 2008, 12 (6), pp 1060–1077
October 28, 2008
Kepner-Tregoe Decision Analysis was used to rank 22 potential routes to a back-up series of compounds in the PDK project. The ten highest scoring routes were evaluated practically, affording four new synthetic sequences for preparing the target compounds.
Journal of the American Chemical Society 2008, 130(44), 14471-14473
October 8, 2008
The kinetics of Pd-catalyzed Tsuji-Trost allylation employing simple phosphine ligands (L = Ar3P, etc.) are consistent with turnover-limiting nucleophilic attack of an electrophilic [L2Pd(allyl)]+ catalytic intermediate. Counter-intuitively, when L is made more electron donating, which renders [L2Pd(allyl)]+ less electrophilic (by up to an order of magnitude), higher rates of turnover are observed...more
The ligand knowledge base approach has been extended to capture the properties of 108 bidentate P,P- and P,N-donor ligands. This contribution describes the design of the ligand set and a range of DFT-calculated descriptors, capturing ligand properties in a variety of chemical environments. New challenges arising from ligand conformational flexibility and donor asymmetry are discussed, and...more
Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.
The manufacture of ZD2249 methoxy sulfoxide (1) using a new project approach is described. Research department processes were scaled up to 100 L if process safety and robustness were not compromised; other factors were treated according to the new approach. Using this strategy, we were able to manufacture a key intermediate on sufficient scale to support delivery of 1 kg quantities of bulk drug...more
Four neurokinin antagonists were assembled using a rapid parallel development approach. Research Department processes were scaled up if process safety and robustness were not compromised. Using this approach, 1 kg of each compound was rapidly delivered for clinical trials.
MUMBAI INDIA APRIL 2015
see............https://www.scientificupdate.co.uk/training/scheduled-training-courses/details/272-Design%20of%20Experiments.html Design of Experiments training course for Chemists and Engineers. I will be running a 3 day training course with Scientific Update on the use of DoE @ the Sea Princess hotel in Mumbai - 13th - 15th APRIL, 2015 INDIA Dr. Paul Murray Director at Paul Murray Catalysis Consulting / Chief Technical Officer at PhosphonicS April 2015. DoE is a statistical tool which enables the efficient exploration of reaction parameters and their effect on a process. The course will introduce the DoE Process and how to use it to develop and understand chemical reactions and processes. The course is aimed at chemists and engineers to help; - increases the efficiency of their work. - develop new processes according to QBD principals. - implement DoE to investigate scale up aspects of chemical processes. http://ow.ly/Iadmp
TRAINING COURSES
EVENT
Title:
Design of Experiments for Chemists and Engineers (DoE)
Industrial Scientists can no longer afford to experiment in a trail-and-error manner, changing one factor at a time. A far more effective method is to apply a systematic approach to experimentation that considers all factors simultaneously.
This approach is called Design of Experiments (DoE) and many scientists use it as an efficient way to solve serious problems afflicting their projects.
DoE provides information about the interaction of factors and the way the total system works, something not obtainable through traditional testing methods. DoE also shows how interconnected factors respond over a wide range of values, without requiring the testing of all possible values directly. DoE is a fundamental aspect of Quality by Design.
The three day course written and presented by Dr Paul Murray a Process Chemist with extensive experience of applying DoE across a wide range of chemical reactions from reaction screening and new route development through to reaction optimisation.
The Course Will empower Scientists to implement DoE in their work to more efficiently improve their processes.
Course Objectives
DoE is a statistical tool which enables the efficient exploration of potential reaction parameters and their effect on a process. DoE is a fundamental aspect of Quality by Design. The course will introduce the DoE Process and how to use it to develop and understand chemical reactions and processess.
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MUMBAI INDIA APRIL 2015
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