PROFESSOR VICTOR SNIECKUS
Manipulating molecules for
medicine
Professor Victor Snieckus is dedicated to the discovery of new methods and technologies for
the synthesis of molecules of significance to pharmaceutical and agrochemical industries for the
development of new medicines for human health and welfare. Here he talks about his work, and
the challenges involved in transferring fundamental discovery to applied chemistry
You are Director of the Snieckus Innovations
Group at Queen’s University in Kingston,
Ontario, Canada. What does this role entail?
Actually, I currently wear two hats: we have
a group carrying out fundamental research in
one building and, down the road, in separate
labs, Snieckus Innovations (SI) which is very
practically orientated. At SI, we essentially
make small molecules for pharmaceutical
companies. Our job entails looking for research
opportunities presented to us either by biotech
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INTERNATIONAL INNOVATION
companies or mid-sized pharmaceutical
companies, or by the corporate types, who
commission us to synthesise molecules for
use in drug development programmes. Such
programmes can be at any phase: the initial
stage, where they don’t know enough about
biological activity and are trying to obtain
some material in order to screen the molecules
to determine if there is a chance of them
developing into a drug; at the in-between stage,
where they need more material and a synthesis
that is scaled up; or at a late stage, where they
have drugs that are going through clinical
trials but whose syntheses could benefit from
efficiency, overcoming use of toxic reagents,
and streamlining into more environmentally
benign processes. SI has an Executive Director,
Michael Wells, who gives us the required
business acumen.
Is there a reason for the companies referring
this process to you, rather than carrying it out
themselves?
Companies have excellent chemists that will
know how to make molecules, but the procedures
may be full of problems for various reasons:
perhaps they put too much waste product out
into the environment, or the procedure could
require too many steps. If the process becomes
too ‘steppy’ (an ‘in word’) it is costly for the
company and may create pollution problems.
In these cases, the companies will come to us
and say “Give us something new”. We thrive on
taking on these kinds of projects! Our aim is to
work on the more complex problems; the more
challenging, the more brain power is needed to
solve a problem, and the more exciting it is for
us! We live for those kinds of projects. However,
as Michael Wells is fond to point out: “We aim
to provide researchers with both the molecules,
and where needed, the know-how, to synthesise
difficult compounds for use in areas as diverse as
biochemistry, agrochemical-biotech, medicinal
chemistry and environmental chemistry. Victor
and his team handle the molecular gymnastics
and I take care of the business matters – it is a
great partnership”.
What sets your group apart from others
working in similar disciplines?
There are many Contract Research Organisations
(CROs) and, since we are one, we face
competition from many sources. Firstly, many
major pharmaceutical companies have either
downsized or are closing, and chemists that are
being fired and offered golden handshakes, start
their own small companies – these are the CROs
that we compete with in North America and
England. The other competition, which is more
serious, comes from China and India, where they
PROFESSOR VICTOR SNIECKUS
have cheaper labour and can therefore undercut
almost anybody. They are far away, however,
and this can cause problems with delivery time
and communication; also, most unfortunately,
there have been issues regarding provision of
pure materials. We expect that some of those
companies will fall out of the picture and some
will improve; it is a changing landscape, but that’s
our competition. We work very hard, and we
have had many cases where a pharmaceutical
company will say, “Here are three molecules, give
us a price; can you do it in four weeks, can you
establish 95 per cent purity on each one?” Once
you have established that you are dependable
they will give you more; that has been our forte,
and that has instilled confidence in our clients
that we shall meet their requirements.
What is catalytic bond coupling and how has it
contributed to your research?
Catalysis is a method for speeding up reactions
and making them more selective. It has been
with us quite a long time: enzymes in our body
are the world’s best catalysts! We are still far
removed on matching what they do but in the
last 30-40 years we have learned a lot about
how to use catalytic reactions to make things
more economical and efficient. Most reactions
today are catalytic processes and new ones
are being discovered faster than the proverbial
speeding bullet. So to be environmentally
responsible, we are like most modern chemists
– we increasingly use catalytic processes in
research and scale-up reactions.
Will there be challenges to overcome in the
coming months? How will you deal with these
challenges in pursuit of your goals?
There is a continuous flow of challenges to
overcome in research – it is never ending. I
learnt in previous years – since starting SI –
that I have to change my frame of reference,
my state of mind, because in the fundamental
work which I am used to, you never give up
some curiosity driven problem. In this kind of
research, however, you start with an idea and no
matter how much effort it takes, 95 per cent of
your work can end in failure. If you are going to
be an organic chemist you had better recognise
when you enter the field that this is what you
are going to face. It is no place for people that
lose faith or become depressed about failure
too fast. That is the problem of the current
generation – they expect solutions fast. You can
be two weeks into a four week project and have
to recognise that you are not going to finish in
time – that you may never get there – and that
is completely against my nature because of
my fundamental background as an academic.
But life is adapting, and I have some very fine
postdocs at SI who helped me to say, “No, that’s
it, Vic, drop the project even if it may involve
taking a loss. There are other clients with orders
that are waiting to be solved. Take these on!”
However, I hasten to add that sometimes these
observations, if followed up by my fundamental
research group, can sometimes turn from
frustrations to opening doors to new discoveries
which would otherwise not have been at all
considered or imagined.
Laying the
foundations
for chemical
innovation
Snieckus Innovations Group at Queen’s University, Ontario, Canada, is
providing critical synthetic assistance to chemists at major pharma and
biotech companies for their discovery and development of potentially
groundbreaking therapeutic agents to fight human diseases and ailments.
THERE IS A continuing need for improved
medicines for conditions as diverse as cancer,
AIDS and Alzheimer’s disease, and innovative
materials for human welfare. To meet these
needs, it initially requires a team of synthetic
chemists striving to build new molecules by
exploiting state-of-the-art strategies and
methods for their evaluation in biological
screening for effectiveness against major diseases
facing mankind. Although the molecules may
be simple or complex, increasingly today they
challenge the synthetic chemists to provide
routes which are efficient, economic and
environmentally benign.
Amongst the leaders in this fascinating field of
constructing organic substances is Professor
Victor Snieckus, winner of multiple awards and
the current Director of Snieckus Innovations (SI) as
well as Bader Chair in Organic Chemistry Emeritus
at Queen’s University. In the fundamental
research laboratories, the Snieckus students and
postdocs are chiefly focused on the discovery
and development of new synthetic methods for
the generation of aromatic and heteroaromatic
compounds, and are working primarily with
carbanionic and transition metal catalysed
reactions. In pursuit of their goals, Snieckus and
his team have received recognition for exploiting
directed ortho metalation (DoM) chemistry as a
crucial conceptual platform for the formulation
of efficient synthetic methods; their applications
in constructing bioactive and natural products
and chiral ligands; and the identification of new
links between DoM and emerging reactions in
organic synthesis. On the other hand, the SI team
aims to meet the needs of small molecules by
pharma and biotech scientists striving to design
and develop the next generation of drugs of value
to human health or to provide more efficient or
new routes for molecules already in the pipeline
as clinical candidates. There is synergy between
the two Snieckus groups: for example, the
fundamental group may have discovered a new
process which is applicable to an ongoing project
molecule by an SI client; on the other hand,
molecules ordered for synthesis in the SI Group
may be challenging in a key step which then,
transferred to the fundamental group, may find
a solution and be of even more general value to
synthetic chemists.
SUPPLY AND DEMAND
The culture within the SI Group is one of
dedicated and patient work regimens in order
to achieve potentially substantial rewards. In
order to meet the constant demand for new
molecules by clients, the SI Group is obliged
to make decisions quickly. In the SI laboratory,
currently consisting of five researchers, while
reactions are percolating constantly in fume
hoods, daily activity involves answering
correspondence from various companies
requesting novel product orders which need to
be completed in a usual timeframe of two to
eight weeks. Upon receipt of an order, Snieckus
and his team assess if the request is viable, they
then seek to calculate the cost and give the
client an accurate and fair quote, before waiting
to hear whether the company in question
would like to proceed. The Group prides itself
in regular communication with the clients,
timely fulfilment of an order, and the provision
of a compound with all proper characterisation,
physical and spectroscopic specifications, and in
high purity.
In extreme situations, the research staff at
the SI Group is forced to tell clients that
certain requests are impossible, either because
the process would be too complicated, too
Over 80 per cent of current therapeutic agents contain some form of
aromatic or heteroaromatic moiety
WWW.RESEARCHMEDIA.EU
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INTELLIGENCE
NEW METHODS IN ORGANIC
SYNTHESIS; FOCUS ON SYNTHETIC
AROMATIC CHEMISTRY
OBJECTIVES
The Snieckus basic research group focuses
on the invention and enhancement of
new organicorganometallic reactions with
emphasis on the directed ortho metalation
(DoM) and transition metal catalysed cross
coupling reactions and their application
to bioactive molecule and natural product
synthesis. These fundamental processes have
been adapted in major pharmaceutical and
biotech companies in their drug discovery
and scale-up process programmes, and some
have become commercial technologies for
eg. anti-AIDS (Dupont), anti-inflammatory
(BMS), antitumor, and antifungal
(Monsanto) agents.
PARTNERS
Monsanto BMS (formerly Dupont and DupontMerck) • Allelix • Eli Lilly
Under Snieckus Innovations: Several
companies (undisclosed)
FUNDING
Fundamental Research: Natural Sciences and
Engineering Research Council of Canada
Snieckus Innovations: contracts, FTEs,
grants, custom synthesis orders from major
pharmaceutical firms
CONTACT
Professor Victor Snieckus Bader Chair in Organic Chemistry Emeritus Department of Chemistry Queen’s University
Chernoff Hall, Room 513 Kingston, Ontario, K7L 3N6, Canada
T +1 613 533 2239
E [email protected]
expensive or unprecedented, or because there is
a lack of essential information. “Occasionally,”
Snieckus explains, “clients give us a request for
a molecule which is excruciatingly complex;
they will demand it in four weeks when the
reality is it requires a whole research project,
a four-year PhD!” In many cases, however, it is
the more challenging proposals which prove to
be the most gratifying to the team of excellent
synthetic chemists, and Snieckus and his team
are thus in constant negotiation between
ambitious optimism and the realistic appraisal
of a request.
blessed with the sometime dubious worth of
instant gratification but, of course, excitement
in knowledge!” He continues: “Most of our
fundamental synthetic work is carried out at
much lower temperatures than the proverbial
‘frozen Canadian North’, that is -78 °C, and all
of our reactions require the use of an argon or
nitrogen atmosphere because many of the used
reagents are sensitive to oxygen rich atmosphere
and have pyrophoric character. However, at SI,
we strive for efficiency and economy and so
try to avoid such cryogenic conditions”. For
determining optimum conditions for reactions
and identifying the products, the modern
battery of available instrumentation includes
high-throughput analysis of multitudes of
reactions, NMR spectroscopy (a fingerprint
for the types of hydrogens and carbons in a
molecule), and an X-ray crystallographic (a
complete picture of the structure).
CURRENT FOCUS
Whilst the priorities of the SI Group are to a large
degree dictated by the requests it receives from
the pharmaceutical and agrochemical industries,
within its current work there is increasing thought
towards the group’s future. As one aim, the team
would like to explore the further potential of
reactions they have discovered – such as the
DoM-Suzuki strategy – which is currently enjoying
significant and widespread attention in numerous
academic and industrial laboratories. With time
constraints and limited manpower currently
at SI, such chemistry may first be undertaken
in Snieckus’ fundamental research group with
appropriate permission and collaboration of the
clients. Through consulting and in lectures at
industry, Snieckus has the rare opportunity as
an academic to become aware of deficiencies
of current synthetic methods and needs for
new modern procedures as expressed by bench
chemists. With agreement from companies, some
of these are brought back to his fundamental
group for testing; while others have resulted in
direct involvement with the SI team in contract
and grant work. Snieckus would like to see major
expansion of such projects and programmes.
TRAINING THE NEXT GENERATION OF CHEMISTS
In addition to his impressive chemical research,
which has earned him numerous awards, Snieckus
is also a dedicated teacher. “My philosophy,” he
reveals, “has always been that I want a student
trained in my lab to be a better chemist than I am; I
want them to develop in maturity and knowledge,
in the techniques we are honing, and to become
all-round excellent scientists in order to proceed
in whatever direction they choose to go.”
The success of this approach has been underlined
by a large proportion of Snieckus’ students
proceeding to take up either academic positions
or leadership roles within the pharmaceutical
industry. In the last six years alone the SI Group
has been involved in the successful training of
68 MSc and PhD students, postdoctoral fellows,
and undergraduates. Through his unconditional
commitment both to developing innovative
practices and to nurturing the next generation
of researchers, Snieckus is making a significant
contribution to the recovery of an exciting time
for the future of synthetic chemistry. He offers
in summary: “My most satisfying moments are
that the fundamental reactions we discover and
publish are noted by industrial chemists and
become relevant in their work to create useful
drugs of the future. That continues to be my
fervent dream”.
TECHNOLOGICAL ADVANCES
As in all fields of scientifically-based
endeavours, advances in synthetic chemistry
are seeing constant, almost daily, revolutions in
Professor Victor Snieckus supporting technologies. “Let’s leave aside the
Director
difficulties that chemists in the early 1900s and
Snieckus Innovations
even 1960s faced in identifying the structure
Innovation Parkof a molecule,” exclaims Snieckus. “What
945, Princess Streettook them months and more recently weeks,
Kingston, Ontario, K7L 3N6, Canada
is achieved in 2013 in half a day. We are now
E [email protected]
www.chem.queensu.ca/people/faculty/
snieckus
www.snieckusinnovations.ca
VICTOR SNIECKUS received his BSc
from the University of Alberta, MSc from
the University of California, Berkeley and
PhD from the University of Oregon. He
was appointed as Assistant Professor at the
University of Waterloo in 1966, held the
Monsanto/NRC Industrial Research Chair
1992-98, and was the Inaugural Bader
Chair in Organic Chemistry at Queen’s
University 1998-2009. His inventions
and methodologies find extensive
application in the pharmaceutical industry.
He continues fundamental research as
Bader Chair Emeritus and is Director of
Snieckus Innovations.
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INTERNATIONAL INNOVATION
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