Asymmetric Synthesis of a Pyrrolizidinone‐Based hNK1 Antagonist through Reductive Ring Contraction of a Six‐Membered Cyclic Nitronate

Asymmetric Synthesis of a Pyrrolizidinone‐Based hNK1 Antagonist through Reductive Ring Contraction of a Six‐Membered Cyclic Nitronate Full article

Journal

European Journal of Organic Chemistry
ISSN: 1434-193X , E-ISSN: 1099-0690

Output data

Year: 2022, Volume: 2022, Number: 41, Article number : e202200796, Pages count : DOI: 10.1002/ejoc.202200796

Authors

Okladnikov Ilya ^1,2 , Boyko Yaroslav ³ , Nelyubina Yulia ⁴ , Ioffe Sema ¹ , Sukhorukov Alexey ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect, 47, 119991 Moscow, Russian Federation
2	D. Mendeleev University of Chemical Technology of Russia,Miusskaya sq., 9, 125047 Moscow, Russian Federation
3	UIUC: Roger Adams Laboratory, Department of Chemistry, University of Illinois, 61801 Urbana, Illinois, United States
4	A. N. Nesmeyanov Institute of Organoelement Compounds,Russian Academy of Sciences, Vavilova str. 28, 119991 Moscow, Russian Federation

A concise seven-step asymmetric synthesis of MSD's potent hNK1 antagonist containing a pyrrolizidinone core bearing two fluorine-substituted aryl groups was developed. The pyrrolizidinone unit was constructed by reductive recyclization of a properly functionalized cyclic nitronate, which was assembled by stereoselective [4+2]-cycloaddition of a nitroalkene with a vinyl ether bearing a Whitesell's chiral auxiliary group. The configuration of the hNK1 antagonist, which was previously suggested based on bioactivity data, was confirmed by X-ray analysis. The crystal structure features multiple weak interactions involving fluorine atoms that are also found in a complex with the hNK1 receptor simulated by molecular docking.

Okladnikov I. , Boyko Y. , Nelyubina Y. , Ioffe S. , Sukhorukov A.
Asymmetric Synthesis of a Pyrrolizidinone‐Based hNK1 Antagonist through Reductive Ring Contraction of a Six‐Membered Cyclic Nitronate
European Journal of Organic Chemistry. 2022. V.2022. N41. e202200796 . DOI: 10.1002/ejoc.202200796 WOS Scopus OpenAlex

Web of science:	WOS:000860075000001
Scopus:	2-s2.0-85138926169
OpenAlex:	W4293785356

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