1130937-72-2Relevant academic research and scientific papers
Synthesis of diastereomeric, deoxy and ring-expanded sulfone analogues of aigialomycin D
Ting, Samuel Z.Y.,Baird, Lynton J.,Dunn, Elyse,Hanna, Reem,Leahy, Dora,Chan, Ariane,Miller, John H.,Teesdale-Spittle, Paul H.,Harvey, Joanne E.
, p. 10581 - 10592 (2013)
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.
Total synthesis of aigialomycin D using a Ramberg - Baecklund/ RCM strategy
Baird, Lynton J.,Timmer, Mattie S. M.,Teesdale-Spittle, Paul H.,Harvey, Joanne E.
supporting information; experimental part, p. 2271 - 2277 (2009/08/07)
The bioactive resorcylic acid lactone aigialomycin D (1) has been synthesized by a novel combination of ring-closing metathesis (RCM) and Ramberg - Baecklund reactions. This synthetic strategy enables the Cl - C2 alkene to be masked as a sulfone during formation of the macrocycle by ring closing metathesis at the C7 - C8 olefin, thus avoiding competing formation of a cyclohexene. A subsequent Ramberg-Baecklund reaction efficiently produces the C1- C2 E-alkene. This combined RCM/ Ramberg-Baecklund reaction strategy should be widely applicable to the synthesis of maerocyclic dienes.
