Synthesis of the QRSTU domain of maitotoxin and its 85-epi- and 86-epi-diastereoisomers.
A devised synthetic strategy toward the QRSTU ring system 4 of the marine-derived biotoxin maitotoxin (1) delivered, in addition to 4, its diastereoisomers 85-epi-QRSTU and 86-epi-QRSTU ring systems 5 and 6. The convergent route to these maitotoxin fragments involved coupling of UT and Q building blocks 9 (obtained from 2-deoxy-D-ribose) and 10 (obtained from D-ribose) followed by ring-closing metathesis to afford enol ether 8, whose elaboration to the targeted QRSTU ring system 4 required its conversion to hydroxy ketone 7. The latter compound (7) was transformed to the final product through a hydroxy dithioketal cyclization, followed by oxidation/methylation of the resulting O,S-mixed ketal to install the last of the five methyl groups contained within the target molecule (4). (13)C NMR spectroscopic analysis of synthesized fragments 4, 5, and 6 and comparisons with maitotoxin provided strong support for the originally assigned structure of the QRSTU domain of the natural product.
Nicolaou
K C
KC
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Gelin
Christine F
CF
Seo
Jae Hong
JH
Huang
Zhihong
Z
Umezawa
Taiki
T
D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D035964:Oxocins / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D000095702:Polyether Toxins
D008387:Marine Toxins; D035964:Oxocins; C020394:maitotoxin; D000095702:Polyether Toxins