Synthesis of acetamides extracted from the Marine Bibalve Codakia orbicularis (Lucinidae)

The "Laboratoire de Chimie Organique et Bioorganique" of the Institut National des
Sciences Appliquées de Lyon belongs to ICBMS (Institut de Chimie et Biochimie
Moléculaires et Supramoléculaires, ICBMS; webpage: http://www.icbms.fr, UMR-CNRS
5246) and is developing innovative research projects at the chemistry-biology interface
associated with methodology, glycochemistry and multistep organic synthesis dedicated to
molecules of therapeutic interest or used in the design of new materials

The team projects are devoted to the development of new synthetic methodology and
its applications to new heterocyclic scaffolds targeting a wide range of enzymes / receptors.
Research is pointing out the development of new heterocyclic scaffolds
using transition metal complexes and their applications to the synthesis of molecules
focusing on pharmaceutical targets (inflammation, anti-coagulants, anti-bacterial agents,
cancer). 

The marine bivalve Codakia orbicularis, harbors endosymbiotic bacteria located in its gill filaments.
Bioassay-guided fractionation of an ethyl acetate extract of the gill tissues led to antibacterial fractions (against
Gram positive and negative bacteria). The bioactive fractions were analyzed using standard chromatographic and
spectrometric methods, revealing in particular a ceramide-like compound isolated for the first time in the
biosphere

In collaboration with our partner in Université des Antilles, Guadeloupe (Dr. F. Goudou & Dr. O. Gros),
the objectives of this internship will address the synthesis of several analogues of this metabolite, for a further
evaluation of their antibacterial activity and putative relationships with structural variations. Indeed different
modifications might be carried out including the degree of hydroxylation, the stereochemistry of the two
stereogenic centers, the length of aliphatic chain and the nature of the fatty acid moiety (Figure 1b).
Whilst many different routes to substituted sphingolipids have been reported, including asymmetric
strategies, alternative sequences will be sought with highly selective steps that might minimize tedious
purification strategies. Aware that variation in the sphingosine core and fatty acid alkyl chains could be
introduced by simple cross metathesis and amine acylation respectively, the generation of a set of
hydroxybutenyl aminoalcohol core scaffolds will be targeted starting from readily available -amino acids.
Benefitting from our experience in multi-step organic synthesis, the intern will specially develop valuable skills in
organic chemistry and for example will be able:
● To optimize conditions according to the parameters screened in synthetic methodology
● To characterize structurally complex molecules according classical routine analytical methods skills (1D and 2D
NMR, mass spectrometry, IR).
● To clearly communicate the results, both in writing in a lab book, in short reports and orally in weekly meetings

The position will be available for five to six months. Appropriate background should include experience in multi-step
organic synthesis and associated analytical skills (NMR, MS, GC, HPLC, UV) will be
appreciated. A good expertise in homonuclear and heteronuclear (1D & 2D) NMR as well as
in the use of classical spectroscopic techniques will also be required. Applications will be
considered from candidates who have (or are expected to obtain) a good degree and level in
organic chemistry.