Efficient Asymmetric Synthesis of the Vasopeptidase Inhibitor BMS-189921

Singh, Jagadish; Kronenthal, David R.; Schwinden, Mark D.; Godfrey, Jollie D.; Fox, Rita; Vawter, Edward J.; Zhang, Bo; Kissick, Thomas P.; Patel, Bhiku; Mneimne, Omar; Humora, Michael; Papaioannou, Chris G.; Szymanski, Walter; Wong, Michael K.; Chen, Chien K.; Heikes, James E.; DiMarco, John; Qiu, Jie; Deshpande, Rajendra P.; Gougoutas, Jack Z.; Mueller, Richard H.

doi:10.1021/ol0352308

Cited by 32 publications

(21 citation statements)

References 42 publications

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“…To prepare the potent vasopeptidase inhibitor (BMS -189921), Singh and coworkers devised a highly enantioselective catalytic hydrogenation of an E / Z mixture of the dehydroamino acid (53) . Based on the literature the reaction was achieved using [Rh -( S,S ) -EtDuphos(COD)] and as expected excellent ee values (99%) were obtained (Scheme 1.19 ) [127] . …”

Section: Synthesis Of Pharmaceutical Intermediatesmentioning

confidence: 85%

Reduction of Functionalized Alkenes

Genêt

2008

Modern Reduction Methods

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Section: Synthesis Of Pharmaceutical Intermediatesmentioning

confidence: 85%

Reduction of Functionalized Alkenes

Genêt

2008

Modern Reduction Methods

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“…The best in this series, a C-7-dimethylazepinone 44g (BMS-189921), demonstrated excellent blood pressure lowering in animal models relevant to ACE or NEP inhibition and its activity was comparable to that of omepatrilat [50]. Recently, an efficient asymmetric synthesis of a clinical candidate BMS-189921 (44g) was accomplished [51].…”

Section: Angiotensin Converting Enzyme (Ace) and Neutral Endopeptimentioning

confidence: 99%

The Application of Freidinger Lactams and their Analogs in the Design of Conformationally Constrained Peptidomimetics

Perdih¹,

Kikelj

2006

CMC

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Peptides exist in solution as an equilibrium mixture of conformers. The backbone conformational constraints are of interest as a means of limiting degrees of freedom and thereby constraining a synthetic peptide into the bioactive conformation. This concept plays an important role in the design of peptidomimetics in the drug development process. In the early eighties, Freidinger proposed the concept of protected lactam-bridged dipeptides, which was a milestone in the design of conformationally constrained peptides. These types of compounds, now widely known as Freidinger lactams, have been of interest to many medicinal and peptide chemists. This review seeks to present the various applications that Freidinger lactams and their hetero-, fused- and unsaturated analogs have found in the design of conformationally constrained peptidomimetics in different therapeutic areas.

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“…1,2 Tiopronin, 3,4 thiolactomycin, [5][6][7] and gliotoxin 8 are leading natural antibiotic compounds. Other representative agents/compounds are listed in chronologic order: antiplatelet activating factor (anti-PAF) antagonists (1991), 9 IMP-1 metallo-β-lactamase inhibitor (1999), 10 vasopeptidase inhibitor (2003), 11 methionine aminopeptidase active cite probes (2004), 12 specific substrate for Streptomyces R61 D,D-peptidases (2005), 13 nonsteroidal farnesoid X receptor agonist (2013), 14 (CNS)-penetrant thiazolidinone CGRP receptor antagonists (2014), 15 agonist for muscarinic M 1 acetylcoline receptor (2015), 16 and fructosyl peptide oxidases inhibitor (2015). 17 Two notable synthetic utilities are addressed (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Chiral syntheses of methyl (R)‐2‐Sulfanylcarboxylic esters and acids with optical purity determination using HPLC

Sasaki

Tanabe

2018

Chirality

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Accessible chiral syntheses of 3 types of (R)-2-sulfanylcarboxylic esters and acids were performed: (R)-2-sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and acid (39%, 96%ee), (R)-2-sulfanylsucciinic diester (59%, 96%ee), and (R)-2-mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and robust method involves (i) clean S 2 displacement of methanesulfonates of (S)-2-hydroxyesters by using commercially available AcSK with tris(2-[2-methoxyethoxy])ethylamine and (ii) sufficiently mild deacetylation. The optical purity was determined by the corresponding (2R,5R)-trans-thiazolidin-4-one and (2S,5R)-cis-thiazolidin-4-one derivatives based on accurate high-performance liquid chromatography analysis with high-resolution efficiency. Compared with the reported method utilizing AcSCs (generated from AcSH and CsCO ), the present method has several advantages, that is, the use of odorless AcCOSK reagent, reasonable reaction velocity, isolation procedure, and accurate, reliable optical purity determination. The use of accessible AcSK has advantages because of easy-to-handle odorless and hygroscopic solid that can be used in a bench-top procedure. The Ti(OiPr) catalyst promoted smooth trans-cyclo-condensation to afford (2R,5R)-trans-thiazolidin-4-one formation of (R)-2-sulfanylcarboxylic esters with available N-(benzylidene)methylamine under neutral conditions without any racemization, whereas (2S,5R)-cis-thiazollidin-4-ones were obtained via cis-cyclo-condensation and no catalysts. Direct high-performance liquid chromatography analysis of methyl (R)-mandelate was also performed; however, the resolution efficiency was inferior to that of the thaizolidin-4-one derivatizations.

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Efficient Asymmetric Synthesis of the Vasopeptidase Inhibitor BMS-189921

Cited by 32 publications

References 42 publications

Reduction of Functionalized Alkenes

Reduction of Functionalized Alkenes

The Application of Freidinger Lactams and their Analogs in the Design of Conformationally Constrained Peptidomimetics

Chiral syntheses of methyl (R)‐2‐Sulfanylcarboxylic esters and acids with optical purity determination using HPLC

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