Total synthesis of brevetoxin A: Part 2: Second generation strategy and construction of EFGH model system

Our second generation strategy for the total synthesis of brevetoxin A involved dissection of the molecule at the ring F oxocene. Synthetically, the F ring formation was expected to occur through Wittig coupling of requisite polycyclic fragments 2 and 3, followed by a hydroxy dithioketal cyclization...

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Published inChemistry : a European journal Vol. 5; no. 2; pp. 618 - 627
Main Authors Nicolaou, KC, Wallace, PA, Shi, SH, Ouellette, MA, Bunnage, ME, Gunzner, JL, Agrios, KA, Shi, GQ, Gartner, P, Yang, Z
Format Journal Article
LanguageEnglish
Japanese
Published BERLIN Wiley 01.02.1999
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
(+)-LAURENCIN
ORGANIC-SYNTHESIS
brevetoxin A
CONVERSION
MEDIUM-RING
total synthesis
CYCLIC ETHERS
EPOXIDE OPENINGS
TETRAHYDROPYRAN SYSTEMS
TECHNOLOGY
synthetic methods
STEREOCONTROLLED SYNTHESIS
SINGLET-OXYGEN
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Summary:Our second generation strategy for the total synthesis of brevetoxin A involved dissection of the molecule at the ring F oxocene. Synthetically, the F ring formation was expected to occur through Wittig coupling of requisite polycyclic fragments 2 and 3, followed by a hydroxy dithioketal cyclization, In order to test this synthetic plan, model phosphonium salt 9 and aldehyde 10 were successfully synthesized and coupled. The deprotected. product (46) was shown to undergo an efficient hydroxy dithioketal cyclization and the product (47) was selectively reduced to the EFGH ring system of brevetoxin A (8), The synthesis of phosphonium salt 9 utilized our cyclic ketene acetal phosphate methodology and a [4+2] addition of singlet oxygen to generate intermediate endoperoxide 11. The success of this model study facilitated a synthetic plan to form and functionalize ring E nonacene and ring F oxocene for the total synthesis of brevetoxin A.
ISSN:0947-6539
DOI:10.1002/(SICI)1521-3765(19990201)5:2<618::AID-CHEM618>3.3.CO;2-9