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.
van Summeren
Ruben P
RP
Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Feringa
Ben L
BL
Minnaard
Adriaan J
AJ
D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism
D007783:Lactones; D018942:Macrolides; C451488:mycolactone A; C451489:mycolactone B