Synthesis of diastereomeric,deoxy and ring-expanded sulfone analogues of aigialomycin D |
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Authors: | Samuel ZY Ting Lynton J BairdElyse Dunn Reem HannaDora Leahy Ariane ChanJohn H Miller Paul H Teesdale-SpittleJoanne E Harvey |
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Institution: | Centre for Biodiscovery, Schools of Chemical and Physical Sciences, and Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand |
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Abstract: | Several analogues of the fungal natural product aigialomycin D (AmD) have been synthesised. These include the stereoisomer 5′R,6′S-AmD, 2,4-di-deoxyAmD, 1′,2′,7′,8′-tetrahydroAmD and a 15-membered macrocyclic sulfone. Growth inhibitory activities of these compounds against the HL-60 leukaemic cell line were measured. The ring-expanded sulfone and tetrahydro-analogue were found to have similar IC50 values to the natural product, whereas the 5′R,6′S-stereoisomer was inactive. Energy minimisation of AmD and the synthesised analogues resulted in a range of lowest energy conformers, from planar, open arrangements of the macrocycle in AmD and tetrahydroAmD to bent, L-shaped structures for the sulfone. The synthesis of methyl orsellinate was investigated and optimised as part of this work. A stereodivergent route to both enantiomers of the diol fragment from d-ribose was also achieved. |
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Keywords: | Aigialomycin D Resorcylic acid lactone Analogue Methyl orsellinate Ramberg&ndash Bä cklund Ring closing metathesis |
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