P ROF . D R A RMANDO C ARLONE

(1)

P ROF . D R A RMANDO C ARLONE

Professore Associato DSFC – Università de L’Aquila

ORCID ID: 0000-0003-2983-6445 https://www.linkedin.com/in/armandocarlone/ Scopus Author ID: 6506442087

(2)

P

UBLICATIONS

1. “Access to pregabalin via asymmetric organocatalysis and flow chemistry - enabling technologies for the cost- effective manufacture of APIs”, A. Carlone*, et al., in preparation.

2. "Diverse Exploitation of Brønsted Acid Catalysts - Paving the Way for Simple Entries to Enantioenriched Amines", A. Carlone*, L. Bernardi*, Highlight, Org. Chem. Front., 2017, 4, 1651-1654.

3. “Process for preparation of eribulin and intermediates thereof”, A. Carlone, L. Bernardi, A. Sinisi, M. E. Fox, Indian Pat. Appl. 2016.

4. “An Autonomous Chemically Fuelled Small-Molecule Motor”, M. R. Wilson, J. Solà, A. Carlone, S. M. Goldup, N.

Lebrasseur, D. A. Leigh, Nature, 2016, 534, 235-240.

[How it works: http://catenane.net/pages/2016_autonomous_motor.html

For highlights of this paper see: ‘No turning back for motorized molecules' (N&Vs), J Clayden, Nature, 34, 187- 188 (2016); ‘Artificial molecular motors: Running on information’ (N&Vs), R D Astumian, Nature Nanotech, published online 13 June 2016; 'Autonomous chemically fueled molecular motor revs up’ (news-of-the-week) [Version in English] [Version in Spanish], Chem & Eng News, 94 (24), 4; ‘Molecular motors start chemically- fuelled journey’ Chem World, published online 9 June; ‘Chemically powered nanomotor goes

autonomous’, Nanotechweb, published online 8 June 2016; 'A chemically powered autonomous molecular nanometer’, PhysOrg, published online 9 June 2016; 'Moleculair verbrandingsmotortje, versie 2’ (in Dutch), C2W, published online 9 June 2016; 'Treno molecole per viaggiare nel corpo’ (in Italian), Corriere della Sera, 10 June 2016; ‘使用化学“燃料”的小分子发动机，两篇《Nature》系牛文赏析’ (in Chinese), X-MOL, 16 June 2016; ‘Cutting-edge chemistry in 2016’ Chem World, 15 Dec 2016]

[For articles on the Italian press: 'Treno molecole per viaggiare nel corpo’, Corriere della Sera, 11 June 2016; 'Treno molecole per viaggiare nel corpo’, Ansa, 11 June 2016]

5. “Organocatalytic Asymmetric Conjugate Additions to Cyclopent-1-enecarbaldehyde: A Critical Assessment of Organocatalytic Approaches towards the Telaprevir Bicyclic Core”, L. Bernardi, M. Fochi, R. Carbone, A.

Martinelli, M. E. Fox, C. J. Cobley, B. Kandagatla, S. Oruganti, V. H. Dahanukar, A. Carlone*, Chem. – Eur. J., 2015, 21, 19208–19222.

[Highlighted on Organic Chemistry Portal]

6. “Kinetic Resolution of Oxazinones: Rational Exploration of Chemical Space through the Design of Experiments”, P. Renzi, C. Kronig, A. Carlone, S. Eröksüz, A. Berkessel, M. Bella, Chem. – Eur. J., 2014, 20, 11768-11775.

7. "Process for preparation of pregabalin", A. Carlone, L. Bernardi, A. Warr, P. de Koning, R. Rajan IN2013CH04788A, 2013.

8. "A Three-Compartment Chemically-Driven Molecular Information Ratchet", A. Carlone, S. M. Goldup, N.

Lebrasseur, D. A. Leigh, A. Wilson, J. Am. Chem. Soc., 2012, 134, 8321-8323.

[Highlighted on: 'Ratcheting up to a molecular motor' JACS Spotlight, June 2012]

9. “A Rotaxane-Based Switchable Organocatalyst", V. Blanco, A. Carlone, K. D. Hänni, D. A. Leigh, B.

Lewandowski, Angew. Chem. Int. Ed., 2012, 51, 5166-5169.

[For highlights of this paper: 'Switchable catalysis' U Lüning, Angew Chem Int Ed, published online 23 July 2012; 'Controlling an organocatalyst with pH' Chem World, 19 April 2012.]

10. "A Small Molecule That Walks Non-Directionally Along a Track Without External Intervention", A. G. Campaña, A. Carlone, K. Chen, D. T. F. Dryden, D. A. Leigh, U. Lewandowska, K. M. Mullen, Angew. Chem. Int. Ed., 2012, 51, 5480-5483.

[Per highlight di questo articolo: 'On the right track' Nature Chem, 4, 430-431 (2012); 'Walk on by: The light at the end of the track' D Bradley, SpectroscopyNow, 15 May 2012; 'A Two-Legged Molecule' Angew Chem Int Ed press report, 24 April 2012]

[Featured on the cover di Angew. Chem. Int. Ed.]

11. “Aminocatalytic Enantioselective anti-Mannich Reaction of Aldehydes with in Situ Generated N-Cbz and N-Boc Imines” C. Gianelli, L. Sambri, A. Carlone, G. Bartoli, P. Melchiorre, Angew. Chem. Int. Ed. 2008, 47, 8700-8702.

[Highlighted on Synfacts, 2009, Issue 1]

12. Review: “Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry” P. Melchiorre, M. Marigo, A. Carlone, G. Bartoli, Angew. Chem. Int. Ed., 2008, 47, 6138-6171.

13. “Quaternary Stereogenic Carbon Atoms in Complex Molecules by an Asymmetric, Organocatalytic, Triple- Cascade Reaction” O. Penon, A. Carlone, A. Mazzanti, M. Locatelli, L. Sambri, G. Bartoli, P. Melchiorre, Chem. –

(3)

Pesciaioli, P. Ricci, L. Sambri, P. Melchiorre, Eur. J. Org. Chem., 2007, 33, 5492-5495.

17. “Organocatalytic Asymmetric α-Selenenylation of Aldehydes” M. Tiecco, A. Carlone, S. Sternativo, F. Marini, G.

Bartoli, P. Melchiorre, Angew. Chem. Int. Ed. 2007, 46, 6882-6885.

18. “Organocatalytic Asymmetric Hydrophosphination of α,β-Unsaturated Aldehydes” A. Carlone, G. Bartoli, M.

Bosco, L. Sambri, P. Melchiorre, Angew. Chem. Int. Ed., 2007, 46, 4504-4506.

19. “A New Approach for an Organocatalytic Multicomponent Domino Asymmetric Reaction” A. Carlone, S. Cabrera, M. Marigo, K. A. Jørgensen, Angew. Chem. Int. Ed., 2007, 46, 1101-1104.

20. “Organocatalytic Asymmetric Friedel-Crafts Alkylation of Indoles with Simple α,β-Unsatured Ketones” G. Bartoli, M. Bosco, A. Carlone, F. Pesciaioli, L. Sambri, P. Melchiorre, Org. Lett., 2007, 9, 1403-1405.

21. “Organocatalytic asymmetric hydrophosphination of nitroalkenes” G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, A. Mazzanti, L. Sambri, P. Melchiorre, Chem. Commun., 2007, 722-724.

22. “Magnesium Perchlorate as Efficient Lewis Acid: A Simple and Convenient Route to 1,4-Dihydropyridines” G.

Bartoli, K. Babiuch, M. Bosco, A. Carlone, P. Galzerano, P. Melchiorre, L. Sambri, Synlett, 2007, 2897-2901.

23. “Reaction of Dicarbonates with Carboxylic Acids Catalyzed by Weak Lewis Acids: General Method for the Synthesis of Anhydrides and Esters” G. Bartoli, M. Bosco, A. Carlone, R. Dalpozzo, E. Marcantoni, P. Melchiorre, L. Sambri, Synthesis, 2007, 3489-3496.

24. “A simple asymmetric organocatalytic approach to optically active cyclohexenones” A. Carlone, M. Marigo, C.

North, A. Landa, K. A. Jørgensen, Chem. Commun., 2006, 4928-4930.

[among the top 50 articles of 2006 – Certified Chem. Commun.]

25. “Organocatalytic Asymmetric Conjugate Addition of 1,3-Dicarbonyl Compounds to Maleimides“ G. Bartoli, M.

Bosco, A. Carlone, A. Cavalli, M. Locatelli, A. Mazzanti, P. Ricci, L. Sambri, P. Melchiorre, Angew. Chem. Int.

Ed., 2006, 45, 4966-4970.

26. “tert-Butyl Ethers: Renaissance of an Alcohol Protecting Group. Facile Cleavage with Cerium(III)

Chloride/Sodium Iodide” G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, E. Marcantoni, P. Melchiorre, L. Sambri, Adv. Synth. Cat., 2006, 348, 905-910.

27. “A New, Mild, General and Efficient Route to Aryl Ethyl Carbonates in Solvent-Free Conditions Promoted by Magnesium Perchlorate” G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, E. Marcantoni,P. Melchiorre, P. Palazzi, L. Sambri, Eur. J. Org. Chem., 2006, 4429-4434.

28. “The First Simple Method of Protection of Hydroxy Compounds as their O-Boc Derivatives under Lewis Acid Catalysis” G. Bartoli, M. Bosco, A. Carlone, R. Dalpozzo, M. Locatelli, P. Melchiorre, P. Palazzi, L. Sambri, Synlett, 2006, 2104-2108.

29. “Alcohols and Di-tert-butyl Dicarbonate: How the Nature of the Lewis Acid Catalyst May Address the Reaction to the Synthesis of tert-Butyl Ethers” G. Bartoli, M. Bosco, A. Carlone, R. Dalpozzo, M. Locatelli, P. Melchiorre, L.

Sambri, J. Org. Chem. 2006, 71, 9580-9588.

30. “Organocatalytic Asymmetric α-Halogenation of 1,3-Dicarbonyl Compounds” G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, P. Melchiorre, L. Sambri, Angew. Chem. Int. Ed., 2005, 44, 6219-6222.

31. “Direct Catalytic Synthesis of Enantiopure 5-Substituted Oxazolidinones from Racemic Terminal Epoxides” G.

Bartoli, M. Bosco, A. Carlone, M. Locatelli, P. Melchiorre, L. Sambri, Org. Lett., 2005, 1983-1985.

32. “Asymmetric Catalytic Synthesis of Enantiopure N-Protected 1,2-Amino Alcohols” G. Bartoli, M. Bosco, A.

Carlone, M. Locatelli, P. Melchiorre, L. Sambri, Org. Lett., 2004, 3973-3975.

33. “Asymmetric Aminolysis of Aromatic Epoxides: A Facile Catalytic Enantioselective Synthesis of anti-β-Amino Alcohols” G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, M. Massaccesi, P. Melchiorre, L. Sambri, Org. Lett., 2004, 2173-2176.

(4)

I

MPEGNO

S

CIENTIFICO E

I

MPEGNO

D

IDATTICO

SCIENTIFIC ACTIVITY

I have been appointed associate professor in organic chemistry at the department of physical and chemical sciences of Università de L’Aquila on 1^st September 2017.

During my time as an industrialist at Dr Reddy’s, my activity and interest were in research and development in organic synthesis. I focused on innovative technologies and methodologies to achieve efficient synthesis of targets that are highly valuable from a biological, pharmaceutical and industrial point of view. I led and managed this in different ways: from hands-on synthesis in the lab to leading teams of researchers, from interactions with other industries to collaborations with academics. I pride myself of my networking skills and of the different networks and consortia that I initiated and took part, despite the historic adversity that industry has in this.

I started my scientific career in 2005 with a PhD in organic chemistry, focusing on asymmetric organocatalysisunder the supervision of Prof. Paolo Melchiorre, in the group of Prof. Giuseppe Bartoli, and a research period spent in the group of Prof. Karl Anker Jørgensen (Aarhus, Denmark), among the world’s top scientists in organocatalysis.

In 2008, I joined the group of Prof. Dave Leigh, world renowned scientist in the field of molecular machines, for my postdoctoral experience and in 2009 I won a Marie Curie Intra European fellowship (SupramolOrganocat ) with a project at the interface of organocatalysis, supramolecular chemistry, and molecular motors.

Since joining industry with Dr Reddy’s in 2011, I focused my efforts in networking, collaborating and carrying out research in organocatalysis to bring it to a level of development so that it could be adopted in industry. In fact, I have demonstrated that it gives a competitive edge in a number of internal projects; some of these projects were taken to a PoC stage in the lab, others were developed at a pilot plant level, and others are currently being implemented in a manufacture environment. My experience of industry has been enriched with knowledge in a large number of different areas, such as patents, Design of Experiments, Quality by Design, optimisation, scale-up, technology transfer, agreements, project management, scrum and kanban workflow, etc.

Highlighted relationships with external partners, during my time at Dr Reddy’s:

- Collaborations and interactions on internal project with: Prof. List (Germany), Prof. Dixon (UK), Prof. Livingston (UK), Prof. Bernardi (Italy), Prof. Melchiorre (Spain), Dr Bures (UK), Prof. Whiting (UK), Prof. Bella (Italy), Prof. Berkessel (Germany), Prof. Cozzi (Italy), Prof. Adamo (Ireland), Prof. Benaglia (Italy), Prof. Bergens (Canada)

- Managing the relationship with Prof. Bernardi as a consultant

- Host to Polyssena Renzi, visiting PhD from Prof. Bella’s group. Publication in CEJ 2014.

- Initiated and managed CHAMPION, an H2020 consortium of 15 EU industrial (Janssen, Bayer, DexLeChem) and academic partners to bring organocatalysis from bench to industry; applied to SPIRE5 call, a highly competitive H2020 funding that only. Score 10/12.

- Partner in ChiralMultCat, FP7 EID with Prof. Bella.

- Partner in SOBER, an ITN network of 10 EU industrial and academic partners to develop boron chemistry.

- Partner in H2020 ITN PHOTOTRAIN, consortium of 13 EU industrial and academic partners to further research in photocatalysis. I am the local coordinator of the project and supervisor of Cristofer Pezzetta, an industrial Marie Curie PhD in photo-organocatalysis in flow. Awarded ITN funding.

Being an active member of the SCI (Society of Chemical Industry) and a proactive member of the scientific community, I have been an invited speaker to a number of talks and seminars, and organised 3 chemistry conferences.

I have also been Cambridge coordinator for Pint of Science, an outreach science festival, that I innovated and developed to an extent that has been publicly commended, as can be seen from my LinkedIn profile.

As a side project, I have been Lead Scientist at Dovetailed (Dovetailed - http://www.dovetailed.io/), an innovative UX design and innovation lab in Cambridge, where I developed business and researched the chemistry and technology for a 3D- printing kitchen robot.

(5)

Supervisor Miriam Wilson, PhD candidate at University of Edinburgh 2010-2011

“An Autonomous Chemically-Fuelled Rotary Motor”

Supervisor Miriam Wilson, master student at University of Edinburgh 2009-2010

“Synthesis of a [2]rotaxane – A model compound for an autonomous motor”

Supervisor Adam Wilson, PhD candidate at University of Edinburgh 2008-2011

“Molecular Information Ratchets”

Supervisor Fabio Pesciaioli, PhD candidate at Università di Bologna 2008

“Asymmetric Aminocatalysis: a Modern Strategy for Molecules, Challenges and Life”

Supervisor Patrizia Galzerano, PhD candidate at Università di Bologna 2007-2008

“New Organocatalytic Asymmetric Strategies: Simple Catalysts For Complex Molecules”

Supervisor Fabio Pesciaioli, master student at Università di Bologna 2007

“Addizioni organocatalitiche asimmetriche a chetoni α,β-insaturi attraverso attivazione via “iminium-ion””

Supervisor Paolo Ricci, master student at Università di Bologna 2006

“Addizioni coniugate asimmetriche di composti 1,3-dicarbonilici a maleimidi”

(6)

C

AREER AND

E

DUCATION

CAREER HISTORY

R&D Scientist, Dr. Reddy’s - Chirotech, Cambridge - UK April 2011 to August 2017 Research and development of innovative technologies and methodologies for the synthesis of drugs or their intermediates, and molecules of industrial interest, through efficient processes.

Cambridge coordinator, Pint of Science, Cambridge - UK Aug 2014 – Aug 2016

Lead Scientist, Dovetailed, Cambridge - UK Jan 2016 – June 2016

Marie Curie Fellow, Prof. D. A. Leigh, University of Edinburgh – UK Postdoctoral Fellow, Prof. D. A. Leigh, University of Edinburgh – UK

March 2009 – Feb 2011 Sep 2008 – Feb 2009

• Molecular motors and machines

• Devised brand new line of research using organocatalysis in supramolecular chemistry

EDUCATION PhD in Chemistry

Prof. Melchiorre, Prof. Bartoli - Università di Bologna, Italy

Jan 2005 – Apr 2008

• PhD Thesis: “Enantioselective Aminocatalysis: New Reactions and New Directions”

• Visiting PhD candidate with Prof. K. A. Jørgensen (Jan-Sep 2006)

• Research in asymmetric organocatalysis with chiral amines Research Fellowship from CINMPIS

Prof. Melchiorre, Prof. Bartoli - Università di Bologna, Italy

Dec 2003 – Nov 2004

• Asymmetric catalytic opening of epoxides

MSc Industrial Chemistry (110/110), Università di Bologna, Italy Sep 1998 – Oct 2003

• 5-year degree (BSc and MSc combined)

• MSc Thesis with Prof. Bernardi, Prof. Ricci

• Visiting research master student with Dr Mangeney, Dr Vrancken at Université PMC - Paris VI, Paris, France (Mar 2003 – Jun 2003)

• Erasmus programme and research on colloidal particles in aqueous media with Prof. Philipse, Dr. Koenderink at Universiteit Utrecht - Utrecht, NL (Sep 2000 – June 2001)

AWARDS AND GRANTS

Marie Curie IntraEuropean Fellowship SupramolOrganocat University of Edinburgh

2009-2011

€ 172 434.64 Research at the interface of organocatalysis, supramolecular chemistry, molecular motors and machines

PHOTOTRAIN H2020 ITN

Dr Reddy’s, Cambridge 2016-2020

€ 3 630 212, 28 Consortium of 13 EU industrial and academic partners to further research in photocatalysis.

Local coordinator of the project and mentor of Cristofer Pezzetta, an industrial Marie Curie PhD in photo-organocatalysis in flow.

INNOVATION AND NETWORKING Cambridge coordinator

Pint of Science

Aug 2014 – Aug 2016

Young Chemist’s Panel Member SCI – Society of Chemical Industry

Sep 2012 - Aug 2016

(7)

C

ONFERENCES AND

T

ALKS

INVITED TALKS

“Industrial chemists: Quo Vadis? A personal story and point of views”, Bologna 24 June 2013

“Asymmetric Catalysis in the Pharmaceutical Industry: From Case Studies to Current Frontiers”

“Microsymposium on Asymmetric Synthesis”, Warsaw, Poland 18 September 2009

“Challenging Asymmetric Catalysis: from Methodology to fuelling Molecular Motors”

“EASE – European Academy for Scientific Explainers”, Genova October 2008

“A researcher’s communicative style analysis for Politicians-Public; Humour in Scientific Presentations - enriching our communication”

“Recent Advances on Asymmetric Catalysis”, Accademia delle Scienze di Bologna January 2008

“Asymmetric Aminocatalytic Reactions”

“EASE – European Academy for Scientific Explainers”, Genova October 2007

“A researcher’s communicative style analysis for Politicians-Public; Humour in Scientific Presentations - enriching our communication”

INVITED SEMINARS

Università degli Studi dell’Aquila, L’Aquila 5 Dec 2016

“Asymmetric organocatalysis - from bench to industry”

Università di Bologna 19 Dec 2014

“Asymmetric Catalysis in the Pharmaceutical Industry: From Case Studies to Current Frontiers”

Università La Sapienza, Roma 1 July 2013

“Asymmetric Catalysis in the Pharmaceutical Industry: From Case Studies to Current Frontiers”

Ecole Nationale Superieure de Rennes – CNRS, Rennes, France 5 Nov 2009

“Challenging Asymmetric Catalysis: from Methodology to fuelling Molecular Motors”

IFC – CNR, Pisa 19 Oct 2009

“Challenging Asymmetric Catalysis: from Methodology to fuelling Molecular Motors”

CONFERENCES ORGANISED

• “The 23rd Annual Review Meeting: Hot Topics in Organic Synthesis”, London, UK - 1 December 2016

• “Crystallisation & Polymorphism for Discovery Chemists”, Cambridge, UK - 16 April 2015

• “Asymmetric Organocatalysis; Challenges and Innovations”, Cambridge, UK - 4 April 2014

SEMINARS ORGANISED AT DR REDDY’S

• Prof. Luca Bernardi “Asymmetric organocatalysis: principles, applications, and new directions” – 12 Sep 2011, and 2 Dec 2016

• Prof. Benjamin List “The Potential of Organocatalysis for Industry” – 11 May 2016

• Prof. Pier Giorgio Cozzi “Mastering the art of enantioselective catalysis: from metal to organocatalytic stereoselective reactions” – 12 March 2015

• Prof. Yujiro Hayashi "Pot-Economy and Organocatalysis in Total Synthesis" – 24 April 2012, and 3 Nov 2014

• Dr Jordi Bures “Reaction Mechanisms in organocatalysis” – 21 May 2014

• Prof. Paolo Melchiorre “Photocatalysis and Organocatalysis” – 3 April 2014

• Prof. Igor Larrosa “Pd, Ag and Au in C-H activation: new transformations for the construction of C-C bonds” – 11 March 2014

• Prof. Dave Carbery “Studies Towards Helical Organocatalysis” – 13 Feb 2013

• Prof. Mauro Adamo “Novel synthetic methodologies to prepare unnatural acids aminoacids and peptidomimetics”

– 16 Aug 2012

• Prof. Darren Dixon “Low loading Organocatalsysis” – 20 March 2013

CONFERENCES ATTENDED

IASOC, Ischia 25-29 September 2016

Poster e selected talk: “Access to pregabalin and telaprevir via asymmetric organocatalysis - an enabling technology for the cost-effective manufacture of APIs”

“The chemistry of organocatalysis”, Sapporo, Japan

Highly prestigious conference reserved to 100 selected attendees

7-9 June 2015

(8)

Poster and short talk: “Access to pregabalin and telaprevir via asymmetric organocatalysis - an enabling technology for the cost-effective manufacture of APIs”

Challenges in Catalysis, London, UK 5 November 2014

Poster: “Asymmetric organocatalysis and hydrogenation – enabling access to telaprevir’s critical fragments”

OrganoCatalysis COST meeting, Palermo 7-10 May 2014

ESOC 2013, Marseille, France 7-12 July 2013

OrganoCatalysis COST meeting, Amsterdam, NL 18-20 April 2013

Talk: “Asymmetric organocatalysis in the pharmaceutical industry: from case studies to current frontiers”

ICCOS, Moscow, Russia 15-20 September 2012

Talk: “Asymmetric organocatalysis in the pharmaceutical industry: from case studies to current frontiers”

Gregynog Synthesis

Conference on organic chemistry where research results that have not been published yet are discussed

23-25 September 2011

Talk: “Efficient Catalytic Technologies for the Manufacture of Single Enantiomer Products”

XXXI SCI Conference, Arcavacata di Rende (CS) 10-14 September 2007

Poster and short talk: “Asymmetric Domino Organocatalytic Reactions”

“Doctoral Programmes in Europe”, Nizza, Francia 7-9 December 2009

Italian Delegate

VI SAYCS, Riccione 9-11 October 2006

Talk: “Enantioselective Organocatalysis as a powerful tool”

XXX Summer Course "A. Corbella", Gargnano 13-17 June 2005

Poster: “Asymmetric aminolysis of aromatic epoxides”

IV Scientific Day CINMPIS 22 October 2004

Talk: “Asymmetric aminolysis of aromatic epoxides”