New approaches towards the synthesis of the side-chain of mycolactones A and B.
New approaches towards the synthesis of the C1'-C16' side-chain of mycolactones A and B from Mycobacterium ulcerans are reported. Chiral building block 4 (Fig. 2) with the correct stereochemistry was obtained starting from naturally occurring monosaccharides, i.e. D-glucose or L-rhamnose. The polyunsaturated moiety 3 was synthesized in only 3 steps from 2,4-dimethylfuran. The building blocks were connected through a Sonogashira coupling resulting in the fast and convergent assembly of an 8,9-dehydro analogue 2 of the side-chain of mycolactones A and B. The synthesis of 1 is at this stage hampered by the lack of a selective partial hydrogenation protocol for alkynes embedded in a conjugated system. Alternative strategies involving palladium catalyzed sp2-sp2 coupling between C7' and C8' or C9' and C10' (Fig. 1) were also explored.
Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Ruben P
RP
van Summeren
Ben L
BL
Feringa
Adriaan J
AJ
Minnaard
D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism
D007783:Lactones; D018942:Macrolides; C451488:mycolactone A; C451489:mycolactone B