135677-47-3Relevant academic research and scientific papers
Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin
Kienle, Maryline,Eisenring, Patrick,Stoessel, Barbara,Horlacher, Oliver P.,Hasler, Samuel,Van Colen, Gwéna?lle,Hartkoorn, Ruben C.,Vocat, Anthony,Cole, Stewart T.,Altmann, Karl-Heinz
, p. 1105 - 1131 (2020/03/10)
A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of sufficient size generally provide for potent anti-Mtb activity of these dihydropyridomycins (minimum inhibitory concentration (MIC) values around 2.5 μM), with several analogs thus approaching the activity of natural pyridomycin. Surprisingly, some of these compounds, in contrast to pyridomycin, are insensitive to overexpression of InhA in Mycobacterium tuberculosis (Mtb). This indicates that their anti-Mtb activity does not critically depend on the inhibition of InhA and that their overall mode of action may differ from that of the original natural product lead.
Syntheses of the Ethyl Esters of the Plant Host-Selective (H-S) Toxins (AF-IIa, AF-IIc and AK-II) Produced by Pathotypes of Alternaria alternata
Crombie, Leslie,Horsham, Mark A.,Jarrett, Sandra R. M.
, p. 1511 - 1524 (2007/10/02)
Total syntheses of the ethyl esters of the host-selective (H-S) toxins produced by Alternaria alternata (strawberry-type pathogen), AF-IIa and AF-IIc, and by the Japanese pear-type AK-II are reported.The initial synthetic objectives, the 2E,4E,6E, 2E,4Z,6E and 2E,4E,6Z stereoisomers of ethyl 8-hydroxy-9-methyldeca-2,4,6,9-tetraenoate, were attained by the use of acetylene hydrometallation and Pd0-mediated vinyl halide coupling: for this purpose tin chemistry was superior to the use of zirconium compounds.The tetraene-hydroxy esters were epoxidised selectively at the 9,10-double bond by the Sharpless procedure under conditions of kinetic control (50percent reaction), which it was predicted would lead to products of predominantly (8R,9S)-stereochemistry.Esterification of the epoxides produced from the 2E,4E,6E and 2E,4E,6Z hydroxy esters with synthetic (2R,3S)-2-(t-butyldimethylsiloxy)-3-methylpentanoic acid, followed by HPLC separation, gave as the major products, stereoisomers which, after deprotection, were characterised as the ethyl esters AF-toxin IIc and AF-toxin IIa.The stereochemical nature of the minor products in the epoxidations is considered.For the sythesis of the AK-II toxin as its ethyl ester, similar esterification with N-acetyl-L-phenylalanine was carried out, except that the racemisation of the amino acid centre ensued.This led to two major products which were separated and identified as (8R,9S,2'S)- and (8R,9S,2'R)-stereoisomers, the former being identical with the ester of AK-II toxin.
