Diapositiva 1

1
P82
mycobacterial lipids availability through
chemical synthesis
Adriaan J. Minnaard, Eva Casas Arce, Bjorn ter
Horst, Jeroen van Wermeskerken, Ben L. Feringa
Stratingh Institute for Chemistry, University of
Groningen, Nijenborgh 4, 9747 AG Groningen, The
Netherlands, A.J.Minnaard_at_rug.nl

• Why prepare mycobacterial lipids using chemical
  synthesis?
• Chemical synthesis makes the compounds available
  in an excellent purity,
• not contaminated with other active compounds
• Chemical synthesis establishes the structure of
  the compound
• In general, chemical synthesis provides
  sufficient quantities for study
• Chemical synthesis provides analogues and
  labeled compounds
• It is much more interesting than prep-HPLC.

Mannose phosphoketide
Mycocerosic acid
Phthioceranic acid
Phthiocerol dimycocerosate (PDIM A)
Chemically prepared analogues of mannose
phosphoketide
How to make mycobacterial lipids using chemical
synthesis? The strategy is to use asymmetric
catalysis. With highly selective metal-catalysts
the synthetic routes can be much shorter and
especially the methyl groups in the chain can be
introduced with excellent stereocontrol. See for
an example the synthesis of phthioceranic
acid. All the lipids presented here have been
prepared or are under construction.
Hydroxyphthioceranic acid (synthesis nearly
finished)
Purity the Maldi-spectrum of PDIM A
Mycolipenic acid (phthienoic acid)
Synthesis of mycocerosic and phthioceranic acid
using asymmetric catalysis
Mycosides (under construction)
Mycolipanolic acid
Phosphomycoketides a) Van Summeren, R.P. Moody,
D.B. Feringa, B.L. Minnaard, A.J. J. Am. Chem.
Soc. 2006, 128, 4546. b) de Jong, A. Casas
Arce, E. Cheng, T.-Y. van Summeren, R.P.
Feringa, B.L. Dudkin, V. Brenner, M. Crich,
D. Matsunaga, I. Minnaard, A.J. Moody, D.B.
Chemistry Biology 2007, 14, 1232. Mycocerosic
acid Ter Horst, B. Feringa, B.L. Minnaard,
A.J. Chem. Comm. 2007, 489. Phthioceranic acid
Ter Horst, B. Feringa, B.L. Minnaard, A.J. Org.
Lett. 2007, 9, 3013. PDIM A Casas Arce, E. Ter
Horst, B. Feringa, B.L. Minnaard, A.J. Chem.
Eur. J. 2008, 14, 4157.