Synthesis of Epoxydine A Analogues Via Palladium-Catalyzed Cyclitolization

Karol Rogelle Francisco*, Yu Li**, George O’Doherty**Barnard College, New York, NY*

Northeastern University, Boston, MA**

BACKGROUND

POSSIBLE DIMERS

RESULTS

FUTURE/ONGOING WORK

Epoxydine A is a naturally occurring compound that has been isolated from a fungus, endophyte salsola oppossifolia. It has been shown to have important anti-bacterial properties that may be pharmacologically important.

Reported [α] = +71.9 (DCM, 0.3)

O

O O

Epoxydine A

Analysis of the NMR and optical rotation data lead the us to believe that the proposed structure is incorrect.

Krohn, K. Helv. Chim. Acta. 2010, 93, 169-174

PROTECTED MONOMERSOO OO

OBoc OPNBzOBoc OBocD DL L

Shan, M., O’Doherty, G. Org. Lett. 2008, 10, 3381-3384.

POSSIBLE STRUCTURES

O

O

O

O

O

OH

Pd(0)(L)2H2O

O

O

O

O

Pd(0)(L)2

O

OH

D-DO

O

O

D D

D

D

O

PdLL

t-BuOCO2

O

PdLL

t-BuOCO2

CYCLITOLIZATION

O

OBocL

O

OBocD

O

OBocL

O

OPNBzD

O

OH

D

O

OHL

O

OHL

O

OHD

O

O

O

L-L

O

O

OD-L

O

O

O

L L

O

O

O

D-L

O

O

OD-L

O

O

O

L D

O

O

O

DD

O

O

O

L L

O

O

O

D L

O

O

OL-L

O

O

O

L-D

O

O

O

DD

O

O

O

D-D

O

O

OL-D

O

O

O

D-L

O

O

OD-D

XX

(S)(S)

O

O(S)(R)

O

(S)(S)

O

O(S)(S)

O

D L

D-D

(R)(S)

O

O(R)(R)

O

(R)(R)

O

O(S)(R)

OL LD-L

(R)(R)

O

O(R)(R)

OL-L

(R)(S)

O

O(R)(S)

OD-D

(R)(S)

O

O(S)(R)

O

(S)(S)

O

O(R)(R)

OD L L D

(S)(R)

O

O(S)(R)

OL L

(S)(S)

O

O(R)(S)

OD D

The spectral data lead us to conclude that the correct structure is either the αL-βL dimer or the αD-βL dimer (or either enantiomer). As our synthesis αD-βL dimer did not match the reported spectral data for epoxydine A, we have concluded that the correct structure is either the αL-βL dimer or its enantiomer (αD-βD).

O

O

O

L L

O

O

OD-D

O

O

O

L D

O

O

O

D-D

O

O

O

D L

O

O

O

D L

The O’Doherty group is currently in the process of synthesizing all 10 analogues of epoxydine A and characterizing them. The group intends to use this antibacterial structure activity relationships to design new antibacterial agents.

ACKNOWLEDGMENTSNortheastern University Chemistry Department National Science FoundationO’Doherty Research GroupDr. Oyinda OyelaranDr. Patricia MabroukDr. Carla MattosProfessor Dina MerrerProfessor Christian RojasDean Michell Tollinchi-MichelCon Edison Research Grant (Barnard College)

DIMERIZATIONO

OBoc

D

Pd catalyst, Ligand

H2O, solvent

O

OHD

O

OBoc

+

O

OH

D L

Pd catalyst, Ligand

solvent O

O

O

D L

Shan, M., O’Doherty, G. Org. Lett. 2010, 12, 2986-2989.