First asymmetric synthesis of the antiepileptic drug Lacosamide (Vimpat®) based on a hydrolytic kinetic resolution strategy

Muthukrishnan, M.; Mujahid, Mohammad; Sasikumar, M.; Mujumdar, Prashant

doi:10.1016/j.tetasy.2011.07.024

Cited by 30 publications

(13 citation statements)

References 19 publications

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“…In this context, a 100% utilization of racemic naphthylglycidyl ether was reported via the preparation of ( R )‐Naftopidil (α 1 ‐adrenergic receptor antagonist) from the resolved epoxide and ( S )‐propanolol (β‐blocker) from the complementary opening product on a gram scale [36e] . The hydrolytic kinetic resolution was also described as key step for the synthesis of the antiepilectic drug Lacosamide [36f] . Worth mentioning is also the use of the kinetic resolution step in total synthesis with the preparation of iso ‐cladospolide achieved from enantiopure propylene oxide [36g] or the synthesis of 7( S ),17( S )‐Resolvin D5, a potent anti‐inflammatory docasonoid from resolved benzylglycidyl ether [36h] .…”

Section: Cobalt‐salen Complexes Intimately Associated With Epoxides mentioning

confidence: 99%

Chiral Cobalt‐Salen Complexes: Ubiquitous Species in Asymmetric Catalysis

Schulz

2021

The Chemical Record

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Since the discovery of their extraordinary reactivity in the hydrolytic kinetic resolution of terminal epoxides about twenty years ago, chiral cobalt‐salen complexes have been shown to be essential for many other asymmetric catalytic reactions. This account summarizes the inspiring works dedicated to the discovery of their new reactivity and their mode of action, as well as the new processes towards the optimization of their cooperativity for bimetallic activation and the implementation of their effective immobilization, including also our contribution on these topics.

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Section: Cobalt‐salen Complexes Intimately Associated With Epoxides mentioning

confidence: 99%

Chiral Cobalt‐Salen Complexes: Ubiquitous Species in Asymmetric Catalysis

Schulz

2021

The Chemical Record

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“…From compound 4a (200 mg 3274,2846,1732,1623,1530,1364,1117, 687 cm -1 . 1 H NMR (400 MHz, CDCl 3 ): δ = 7.45-7.12 (m, 5 H), 6.91 (br s, 1 H), 6.52 (d,J = 6.4 Hz,1 H),4.49 (td,J = 7.3,4.3 Hz, 1 H), 4.43 (dd, J = 15.0, 6.1 Hz, 1 H), 4.34 (dd, J = 15.0, 5.6 Hz, 1 H), 3.74 (dd, J = 9.2, 4.3 Hz, 1 H), 3.52-3.36 (m, 3 H), 1.94 (s, 3 H), 1.07 (t, J = 7.0 Hz, 3 H).…”

Section: (R)-2-acetamido-n-benzyl-3-ethoxypropanamide (1a)mentioning

confidence: 99%

Synthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate

Jeong

Yadav

2016

Synthesis

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An efficient and scalable synthesis of the antiepileptic drug (R)-lacosamide and its derivatives has been achieved from commercially available aziridine-(2R)-carboxylate in three simple sequential steps, including regioselective aziridine ring opening, debenzylation followed by acetylation in one pot, and amide formation. The advantage of this protocol is that the starting material and reagents are commercially available and a single purification by recrystallization is required after all the chemical transformations, providing the final drug in >99.9% ee.

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“…166 Among these examples, most were synthesised from chiral epoxides, but applications of the ring-opened chiral 1,2-diols were also reported. In addition to these natural products, the cobalt-catalysed kinetic resolution of epoxides has also been used for the straightforward synthesis of drugs, including (R)-lacosamide (77), 167 (R)-mexiletine (78), 168 enciprazine (79) 169 and amprenavir (80). 170 In the synthesis of 77 and 78, the chiral secondary alcohol of the chiral diol was transformed into the corresponding amine functionality.…”

Section: Syn Thesismentioning

confidence: 99%

“…324 The second is an enantioselective intramolecular tandem cyclisation of 2-dialkylaminobenzylidene malonates. 324 Thereby, a 1,5-hydride transfer initialises an asymmetric cyclisation, resulting in optically active tetrahydroquinolines (167) in good yields and enantioselectivities; the absolute configuration, however, was not determined (Scheme 90).…”

Section: Syn Thesismentioning

confidence: 99%

Cobalt-Catalysed Bond Formation Reactions; Part 2

Röse

Hilt

2015

Synthesis

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This review summarises the cobalt-catalysed reactions of the years 2008 through 2014. Covered are addition reactions, such as the hydrogenation of double bonds, the addition of C-H bonds to double and triple bonds, C-H activation reactions, cobalt-catalysed cross-coupling reactions and selected additions of H-B and H-Si bonds to unsaturated starting materials. The cobalt-catalysed cycloadditions range from cyclopropanations, [2+2], Pauson-Khand reactions, [2+2+2], [4+2], [6+2] cycloadditions as well as benzannulations. Also covered are Nicholas reactions, cobalt-catalysed Jacobsen's kinetic resolution of epoxides as well as selected miscellaneous cobalt-catalysed processes mainly for carbon-carbon bond formations. 1 Introduction 2 Addition Reactions 3 Homo-and Cross-Coupling Reactions 4 Jacobsen Kinetic Resolution of Epoxides 5 Nicholas Reactions 6 Cycloaddition Reactions 7 Miscellaneous 8 Conclusion

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First asymmetric synthesis of the antiepileptic drug Lacosamide (Vimpat®) based on a hydrolytic kinetic resolution strategy

Cited by 30 publications

References 19 publications

Chiral Cobalt‐Salen Complexes: Ubiquitous Species in Asymmetric Catalysis

Chiral Cobalt‐Salen Complexes: Ubiquitous Species in Asymmetric Catalysis

Synthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate

Cobalt-Catalysed Bond Formation Reactions; Part 2

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