Efficient total synthesis of pulchellalactam, a CD45 protein tyrosine phosphatase inhibitor.
A new approach to a CD45 protein tyrosine phosphatase inhibitor, pulchellalactam, is described. The key step of the sequence involves addition and elimination of an enolic lactam in a single step and 70% yield, employing an organocuprate reagent. The resulting alpha,beta-unsaturated lactam could be condensed with isobutyraldehyde to produce Z-pulchellalactam or converted into siloxypyrrole, which was subjected to the BF(3) x Et(2)O-promoted coupling reaction with isobutyraldehyde to afford E-pulchellalactam after E1-cB elimination and TFA deprotection. This first total synthesis afforded Z-pulchellalactam in six steps and 32% overall yield from Boc-glycine. The same sequence of reactions could also be applied to the liquid- or solid-phase synthesis of trifunctionalized pulchellalactam derivatives.
Li
Wen-Ren
WR
Department of Chemistry, National Central University, Chung-Li, Taiwan 32054, ROC. ch01@ncu.edu.tw
Lin
Sung Tsai
ST
Hsu
Nai-Mu
NM
Chern
Meei-Shiou
MS
D002625:Chemistry, Organic / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007769:Lactams; C113327:pulchellalactam; C029052:BOC-glycine; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D005998:Glycine