My research interests are in the broad field of organic synthesis
James R. Vyvyan
My research interests are in the broad field of organic synthesis.
Projects in my group range from developing new synthetic methods and asymmetric reactions to the total synthesis of natural products possessing interesting structural features and biological properties. Our work requires detailed analysis of
NMR spectra to characterize synthetic intermediates and we frequently use molecular modeling to develop synthetic strategies.
Research Projects
The Heliannuols and Related Compounds: Natural Herbicide Models
The
heliannuols (1-12) are a family of sesquiterpene natural
products isolated in small quantities from the sunflower (Helianthus
annuus) and selectively inhibit the germination and growth of other
plants. Efficient synthesis of the heliannuols and simpler structural
analogues will allow further studies of their applications in agriculture.
In addition to their biological properties, their unusual structures make
the heliannuols challenging synthetic targets. Palladium-catalyzed
cross-coupling of organozinc reagents to aryl halides and alkenyl triflates
provide the necessary functionality to synthesize all of the heliannuols
from a common aromatic core.
To date, our approach to
closing the medium ring ether moiety of these compounds involves nucleophilic
attack of a phenol on an epoxide. We have completed syntheses of heliannuols C,
D, and E (3-5) and are now pursuing the other members of this
family, related compounds such as helianane (13) and halogenated
derivatives 14 and 15 that have been isolated from marine
sources. Our efforts now focus on new approaches to the 8-membered cyclic ether
present in heliannuols A, K and L (1, 11, and 12) and the
heliananes (13-15) using both C—C and C—O bond forming processes.
Total Synthesis of
Pyridine Alkaloid Natural Products
Cananodine (16) is a
guaipyridine alkaloid isolated from Cananga odorata (ylang-ylang)
whose oil is used in folk medicine. This compound exhibits encouraging activity
against two types of liver cancer. Another cytotoxic pyridine alkaloid,
lycopladine A (17), is also of interest.
We are interested in
developing an enantioselective aromatic Claisen rearrangement of an achiral
aryl allyl ether. There only a few reports of such a transformation, and
they lack substrate generality. We are examining various Lewis acids
complexed to chiral ligands such as pybox and substituted BINOLs. Even after
catalysts systems that provide appreciable enantiomeric excess are found, a
greater challenge is achieving catalyst turnover, as many catalysts
coordinate more strongly to the phenol product than to the starting ether.
