Stereochemical definition and chirospecific synthesis of the peptide deformylase inhibitor Sch 382583.
The recently reported natural product Sch 382583 (1), an inhibitor of peptide deformylase, has been synthesized in 16 steps from commercially available starting materials. The three chiral centers were set by a combination of chiral auxiliary and chiral pool approaches. The succinate 5 and piperazic acid 9 moieties were obtained by Evans oxazolidinone imide enolate alkylation and hydrazination/cyclization, respectively, and the aminohexanone side chain 13 was prepared via Grignard substitution of the Weinreb amide derived from l-valine. Spectroscopic data for the resulting synthetic material, compared with the data reported for the natural product, established that the previously unassigned valine ketone stereocenter (C-4) has the S-configuration.
Stine-Haskell Research Center, DuPont Crop Protection, 1090 Elkton Road, Newark, Delaware 19711, USA.
Reed A
RA
Coats
Sheng-Lian
SL
Lee
Kari A
KA
Davis
Kanu M
KM
Patel
Elaine K
EK
Rhoads
Michael H
MH
Howard
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D003500:Cyclization; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006588:Hexanones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013386:Succinates / Q000737:chemistry
D004151:Dipeptides; D004791:Enzyme Inhibitors; D006588:Hexanones; D011724:Pyridazines; C484624:Sch 382583; D013386:Succinates; C014756:piperazic acid; D000581:Amidohydrolases; C084507:peptide deformylase