Iso-migrastatin congeners from Streptomyces platensis and generation of a glutarimide polyketide library featuring the dorrigocin, lactimidomycin, migrastatin, and NK30424 scaffolds.
Iso-Migrastatin (10) has been shown to be the main natural product of Streptomyces platensis, which undergoes a facile, H2O-mediated rearrangement into dorrigocin A (2), 13-epi-dorrigocin A (11), dorrigocin B (3), and migrastatin (1). Eight new congeners (12-19) of 10 were characterized. They can undergo the same H2O-mediated rearrangement into the corresponding 1, 2, 3, and 11 analogues (20-43) or 1,4-Michael addition with cysteine to afford the corresponding analogues (44-51) of NK30424 A and B (5, 6). This study generated a 47-member library of glutarimide polyketides, setting the stage to investigate the SAR for this family of natural products. These results also established the absolute stereochemistry of 5 and 6 and shed new light into the post-polyketide synthase steps for 10 biosynthesis.
Ju
Jianhua
J
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Lim
Si-Kyu
SK
Jiang
Hui
H
Seo
Jeong-Woo
JW
Shen
Ben
B
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010881:Piperidones / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D007783:Lactones; D018942:Macrolides; C449032:NK30424A; D010881:Piperidones; C089606:dorrigocin A; C089607:dorrigocin B; C455261:isomigrastatin; C077633:lactimidomycin; C007864:glutarimide