Open AccessSynthesis of Anhydroryanodol
Author(s) -
Kang Du,
Matthew J. Kier,
Zachary D. Stempel,
Valer Jeso,
Arnold L. Rheingold,
Glenn C. Micalizio
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c05766
Subject(s) - chemistry , annulation , natural product , total synthesis , metallacycle , alkyne , intramolecular force , enyne , combinatorial chemistry , stereochemistry , stereoselectivity , organic synthesis , organic chemistry , catalysis , x ray crystallography , physics , diffraction , optics
A stereoselective entry to ryanoids is described that culminates in the synthesis of anhydroryanodol and thus the formal total synthesis of ryanodol. The pathway described features an annulation reaction conceived to address the uniquely complex and highly oxygenated polycyclic skeleton common to members of this natural product class. It is demonstrated that metallacycle-mediated intramolecular coupling of an alkyne and a 1,3-diketone can proceed with a highly functionalized enyne and with outstanding levels of stereoselection. Furthermore, the first application of this technology in natural product synthesis is demonstrated here. More broadly, the advances described demonstrate the value that programs in natural product total synthesis have in advancing organic chemistry, here through the design and realization of an annulation reaction that accomplishes what previously established reactions do not.