MarinLit: Database and essential tools for the …bulletin.acscinf.org/PDFs/247nm25.pdfModern NMR...
Transcript of MarinLit: Database and essential tools for the …bulletin.acscinf.org/PDFs/247nm25.pdfModern NMR...
MarinLit: Database and essential
tools for the marine natural
products community Serin Dabb, Royal Society of Chemistry
John Blunt & Murray Munro, University of
Canterbury
Literature Updating Services
Databases
• The Merck Index* Online
• Recently acquired MarinLit
Open Access
Open Data
Royal Society of Chemistry
Publishing
• Indexes all literature related to marine natural products (compounds found in marine environments)
• 26K articles (MARINe LITerature)
• Structure searchable compound database • 24K compounds
• Data (taxonomy, location, chemical)
• Dereplication tool
History
• Community developed database from University
of Canterbury, New Zealand
• Built by John Blunt and Murray Munro
Sep-2013
Apr-2014
Announcement Launch
Content selection
• No set source list
• Articles Biological activity, chemistry, culturing,
ecological, geography, pharmacology, synthesis
• Compounds Only indexed when: First isolated, new to marine,
structural revision
Bibliographic search
“Dereplication”
Dereplication in MarinLit
Can be achieved using
• 1H NMR features e.g. number of Me groups
• 13C and 1H chemical shifts
• Molecular formula (complete or partial)
• UV maxima
• Exact mass
OR a combination of any or all of the above.
Why is it important? “A conservative estimate would be that it takes an experienced NP chemist about three months to fully elucidate a structure…. We estimate these costs to be around $15 000 (personnel time, solvents, NMR/MS recharge, media, columns, etc.).
These estimates are for one structure, under the most ideal conditions. These costs can be easily lowered when dereplication can be accomplished or quickly raised for complex molecules with poor chromatographic properties produced in low overall titer. For some molecules the cost of complete structure elucidation can be over one million dollars.”
P. Dorrestein et al., Nat. Prod. Rep., 2014, 31, 718
Saves
time
New drugs
Advantages of 1H NMR
features
• Based on pattern recognition, so quickly
discriminatory
• Based only on the number of each type of feature
• Independent of NMR solvent, temperature and pH
• Can be combined with 2D NMR experiments to get
further information.
1H NMR Spectrum of Unknown. Is it a new compound
or is it known?
9 Me groups are obvious (from integrals)
Search of MarinLit: 9 Me gave 628 answers
4 Me singlets 4 Me doublets
1 OMe singlet
Aromatic protons
On examination these can be characterised as shown
On searching MarinLit for 9 total methyls: 4 singlets, 4 doublets, 1 OMe there
were 39 answers, but there are also aromatic protons that can be used
COSY spectrum
This implies a 1,2,4-trisubstituted
aromatic system
A broad singlet coupled/on-coupled to 2 doublets
4 Me singlets 4 Me doublets
1 OMe singlet
4 singlets, 4 doublets, 1 OMe, 1,2,4-trisubstituted aromatic 2
answers
Comparison of
NMR data
confirmed that the
unknown had this
structure
Due to be published early 2015
Modern NMR Approaches To The Structure Elucidation of Natural Products
Complete set ISBN 978-1-84973-459-2
Volume 1: Instrumentation and Software, ISBN 978-1-84973-518-6
Volume 2: Data Acquisition and Applications to Compound Classes,
ISBN 978-1-84973-393-9
Edited by Antony Williams,
Gary Martin, Merck, USA
David Rovnyak, Bucknell University, USA
www.rsc.org/books
New Book from the Royal Society
of Chemistry
Future plans
• Location
searching
?
Marine
Marine
Terrestrial
Microbial Animal
Plant
THE
MERCK INDEX
NEW
15th
Edition
*The name THE MERCK INDEX is owned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., and is licensed to The Royal Society of Chemistry for use in the U.S.A. and Canada.
Questions?
@SerinDabb
Pioneering Series
New Developments in NMR Editor in Chief: William S Price, University of Western Sydney
Series Editors: Bruce Balcom, University of New Brunswick
István Furó, KTH Royal Institute of Technology, Sweden
Maili Liu, Chinese Academy of Sciences
Masatsune Kainosho, Nagoya University, Japan
Focus is on novel aspects of method and instrumentation
development, applications in emerging fields and new techniques
and technologies.
http://rsc.li/nmr