Synthesis of (-)-PNU-286607 by Asymmetric Cyclization of Alkylidene Barbiturates

被引：148

作者：

Ruble, J. Craig ^{[1
]}

Hurd, Alexander R. ^{[2
]}

Johnson, Timothy A. ^{[3
]}

Sherry, Debra A. ^{[2
]}

Barbachyn, Michael R. ^{[2
]}

Toogood, Peter L. ^{[2
]}

Bundy, Gordon L. ^{[1
]}

Graber, David R. ^{[1
]}

Kamilar, Gregg M. ^{[1
]}

机构：

[1] Pharmacia Corp, Infect Dis Med Chem, Kalamazoo, MI 49001 USA

[2] Pfizer Global Res & Dev, Antibacterial Chem, Ann Arbor, MI 48105 USA

[3] Pfizer Global Res & Dev, Antibacterial Chem, Groton, CT 06340 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 11期

关键词：

HETEROCYCLIC SYNTHESIS; ANTIBIOTIC-RESISTANCE; AMINO; FUNCTIONALIZATION; DISCOVERY;

D O I：

10.1021/ja808014h

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

PNU-286607 is the first member of a promising, novel class of antibacterial agents that act by inhibiting bacterial DNA gyrase, a target of clinical significance. Importantly, PNU-286607 displays little cross-resistance with marketed antibacterial agents and is active against methicillin-resistant staphylococcus aureus (MRSA) and fluoroquinoline-resistant bacterial strains. Despite the apparent stereochemical complexity of this unique spirocyclic barbituric acid compound, the racemic core is accessible by a two-step route employing a relatively obscure rearrangement of vinyl anilines, known in the literature as the "tert-amino effect." After a full investigation of the stereochemical course of the racemic reaction, starting with the meso cis-dimethylmorpholine, a practical asymmetric variant of this process was developed.

引用

页码：3991 / 3997

页数：7

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