An efficient synthesis of a heterobifunctional coupling agent.
An efficient synthesis of 4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]-N-(6-[[6-([6-[(2,5-dioxopyrrolidin-1-yl)oxy]-6-oxohexyl]amino)-6-oxohexyl]amino]-6-oxohexyl)cyclohexanecarboxamide (12), a heterobifunctional coupling agent, was developed, which is critical for chemoselective conjugation of proteins and enzymes. The synthesis involved seven steps starting from 6-{[(benzyloxy)carbonyl]amino}hexanoic acid (1), and multigram quantities of coupling agent (12) were prepared using this protocol in excellent overall yield and 99.6% purity by reversed phase HPLC. The new method is suitable for the synthesis of coupling agent 12, consistently with purity >99%, and is useful for the preparation of other analogous coupling agents.
Reddy
Rajarathnam E
RE
Core R&D Chemistry Group (Department 09MD, Building AP20), Diagnostics Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6016, USA. rajarathnam.reddy@abbott.com
Chen
Yon-Yih
YY
Johnson
Donald D
DD
Beligere
Gangamani S
GS
Rege
Sushil D
SD
Pan
You
Y
Thottathil
John K
JK
D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry
C506453:4-((2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl)-N-(6-((6-((6-((2,5-dioxopyrrolidin-1-yl)oxy)-6-oxohexyl)amino)-6-oxohexyl)amino)-6-oxohexyl)cyclohexanecarboxamide; D003432:Cross-Linking Reagents; D011758:Pyrroles; D011759:Pyrrolidines