Design and synthesis of a library of tetracyclic hydroazulenoisoindoles.
Forty-four tetracyclic hydroazulenoisoindoles were synthesized via a tandem cyclopropanation/Cope rearrangement, followed by a Diels-Alder sequence from easily available five-membered cyclic cross-conjugated trienones. These trienones were obtained from two different routes depending upon whether R(1) and R(2) are alkyl or amino acid derived functional groups, via a rhodium(I)-catalyzed cycloisomerization reaction. To increase diversity, four maleimides and two 1,2,4-triazoline-3,5-diones were used as dienophiles in the Diels-Alder step. Several Diels-Alder adducts were further reacted under palladium-catalyzed hydrogenation conditions, leading to a diastereoselective reduction of the trisubstituted double bond. This library has demonstrated rapid access to a variety of structurally complex natural product-like compounds via stereochemical diversity and building block diversity approaches.
Brummond
Kay M
KM
Center for Chemical Methodologies & Library Development, Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. kbrummon@pitt.edu
Mao
Shuli
S
Shinde
Sunita N
SN
Johnston
Paul J
PJ
Day
Billy W
BW
D000818:Animals; D002384:Catalysis; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry; D006865:Hydrogenation; D051379:Mice; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000187:drug effects; D012238:Rhodium / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D006576:Heterocyclic Compounds, 4 or More Rings; D011965:Receptors, Glucocorticoid; D054852:Small Molecule Libraries; D010165:Palladium; D012238:Rhodium