Total Synthesis of Natural Products: At the Frontiers of Organic Chemistry

297 Pages·2012·19.1 MB·English

by  Kevin M. Peese

Total Synthesis of Natural Products
.
Jie Jack Li (cid:129) E.J. Corey
Editors
Total Synthesis of Natural
Products
At the Frontiers of Organic Chemistry
Editors
JieJackLi E.J.Corey
NewJersey HarvardUniversity
USA Dept.ofChemistryandChemicalBiology
Cambridge
USA
ISBN978-3-642-34064-2 ISBN978-3-642-34065-9(eBook)
DOI10.1007/978-3-642-34065-9
SpringerHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2012955413
#Springer-VerlagBerlinHeidelberg2012
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Dedicated to
Professor David Y. Gin (1967–2011)
.
Preface
The last few decades have witnessed some exciting developments of synthetic
methodologies in organic chemistry. Chiefly among these developments are ring-
closing metathesis (RCM) and transition metal-catalyzed C–H activation, which
haveemergedasnovelandusefultools.
A touchstone for any synthetic methodology is how practical it is in synthesis,
especially total synthesis of natural products. Therefore, it is not surprising that
books on total synthesis occupy a place on nearly every organic chemist’s
bookshelf.
Thisvolumeissomewhatdifferentfrompreviousbooksontotalsynthesis.We
havebeenfortunateenoughtoenlistelevencurrentpractitionersinthefieldoftotal
synthesis to describe one of their best total syntheses. These authors leveraged
synthetic methodologies developed in their own laboratories as key operations in
their construction of natural products. As such, this book reflects a true sense of
whatishappeningatthefrontiersoforganicchemistry.
Skillman,NJ,USA JieJackLi
Cambridge,MA,USA E.J.Corey
vii
.
Contents
1 Nominine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
KevinM.PeeseandDavidY.Gin
1.1 IntroductionandClassification. . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Pharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 Biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.4 PreviousSyntheticWork. . . . . .. . . . .. . . . . .. . . . . .. . . . . .. 3
1.4.1 TotalSynthesisofNominine[19a]. . . . . . . . . . . . . . . . . 4
1.4.2 SyntheticStudiesTowardtheHetisineAlkaloids. . . . . . . 6
1.5 StrategyandRetrosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.6 Synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.7 CompleteSynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2 Nakiterpiosin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
ShuanhuGaoandChuoChen
2.1 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.2 Synthesisofthe6,6,5,6SteroidalSkeleton. . . . . . . . . . . . . . . . . 26
2.2.1 TheBiomimeticApproaches. . . . . . . . . . . . . . . . . . . . . 27
2.2.2 TheRing-by-RingApproaches. . . . . . . . . . . . . . . . . . . . 28
2.2.3 Miscellaneous. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.3 SynthesisofNakiterpiosin.. . . . .. . . . . .. . . . .. . . . .. . . . . .. 31
2.4 BiologyofNakiterpiosin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3 TheKinamycins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
SethB.Herzon
3.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.2 StructureElucidation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.3 BiologicalActivityandMechanismofActionStudies. . . . . . . . 43
3.4 BiosynthesesoftheKinamycins. . . . . . . . . . . . . . . . . . . . . . . . 45
ix