TY - JOUR
T1 - Stereoselective synthesis of pyroglutamate natural product analogs from α-Aminoacids and their anti-cancer evaluation
AU - Tekkam, Srinivas
AU - Alam, Mohammad A.
AU - Just, Matthew J.
AU - Berry, Steven M.
AU - Johnson, Joseph L.
AU - Jonnalagadda, Subash C.
AU - Mereddy, Venkatram R.
PY - 2013/12
Y1 - 2013/12
N2 - Alkylation of α-amino acid derived iminoesters with Baylis-Hillman (BH) reaction template based allyl bromides/allyl acetates followed by acidic hydrolysis furnished α-methylene-β-substituted-pyroglutamates and α-alkylidene pyroglutamates respectively. Application of these methodologies has been demonstrated in the synthesis of fused [3.2.0]-γ-lactam-β-lactones. Further, substrate controlled stereoselective alkylation of L-threonine derived oxazoles with BH reaction based allyl bromides and acetates yielded optically pure α-methylene-β-substituted pyroglutamates, and α-alkylidene pyroglutamates. These methodologies have been applied in the preparation of chiral [3.2.0] heterobicyclic pyroglutamates containing hydroxyethyl side chain. All the synthesized pyroglutamates have been evaluated for their anti-cancer and enzyme proteasome inhibition activity.
AB - Alkylation of α-amino acid derived iminoesters with Baylis-Hillman (BH) reaction template based allyl bromides/allyl acetates followed by acidic hydrolysis furnished α-methylene-β-substituted-pyroglutamates and α-alkylidene pyroglutamates respectively. Application of these methodologies has been demonstrated in the synthesis of fused [3.2.0]-γ-lactam-β-lactones. Further, substrate controlled stereoselective alkylation of L-threonine derived oxazoles with BH reaction based allyl bromides and acetates yielded optically pure α-methylene-β-substituted pyroglutamates, and α-alkylidene pyroglutamates. These methodologies have been applied in the preparation of chiral [3.2.0] heterobicyclic pyroglutamates containing hydroxyethyl side chain. All the synthesized pyroglutamates have been evaluated for their anti-cancer and enzyme proteasome inhibition activity.
KW - Baylis-hillman reaction
KW - Boronic acids
KW - Diastereoselective dihydroxylation
KW - Heterobicyclic compounds
KW - Lactonization
KW - Pyroglutamates (γ-carboxy-γ-lactams)
KW - Regioselective regioselective deoxygenation
KW - Substrate controlled alkylation
KW - Threonine derived oxazole
UR - http://www.scopus.com/inward/record.url?scp=84899029987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899029987&partnerID=8YFLogxK
U2 - 10.2174/18715206113139990097
DO - 10.2174/18715206113139990097
M3 - Article
C2 - 23848201
AN - SCOPUS:84899029987
SN - 1871-5206
VL - 13
SP - 1514
EP - 1530
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
IS - 10
ER -
