Abstract：
:The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890. Their structures were determined by one- and two-dimensional NMR studies and mass spectrometry. Among these compounds, two natural analogues 2-3 which possessed acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1. This indicates that the acyl beta-HyLeu residue plays an important role in activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha residue is not critical to activity. The other hydrogenated derivative 5 had significantly less activity, which could be attributed to conformational differences.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Taniguchi M,Suzumura K,Nagai K,Kawasaki T,Takasaki J,Sekiguchi M,Moritani Y,Saito T,Hayashi K,Fujita S,Tsukamoto S,Suzuki Kdoi
10.1016/j.bmc.2004.04.006subject
Has Abstractpub_date
2004-06-15 00:00:00pages
3125-33issue
12eissn
0968-0896issn
1464-3391pii
S0968089604002822journal_volume
12pub_type
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