Synthesis of enantiomerically pure 3-aminochroman derivatives

Usse, Stéphanie; Pavé, Grégoire; Guillaumet, Gérald; Viaud‐Massuard, Marie‐Claude

doi:10.1016/s0957-4166(01)00202-6

Cited by 14 publications

(6 citation statements)

References 20 publications

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“…The same route was applied to alcohols 6c and 8c , affording amines ( R )- 2 ([α] D 25 = −13.3° ( c 1.5, CHCl 3 ) lit . [α] D 25 = −13.7° ( c 1.0, CHCl 3 )) and ( S )- 3 (( S )- 3· HCl [α] D 25 = −60.3° ( c 1.3, MeOH) lit . [α] D 25 = −61.0° ( c 2.3, MeOH)) with similar yields.…”

Section: Resultsmentioning

confidence: 99%

“…5 In addition to these relevant targets, also the 1R,3′S diastereoisomer of amine 4 (key precursor of chromanyl analogues of NK-1 tachykinin receptor antagonist 6 recently developed by Eli Lilly) was taken into consideration as a part of our ongoing research program, which is devoted to the syntheses of biologically active molecules by means of biocatalytic methodologies. 7,8 So far, amine 2 and its derivatives have been prepared by starting from the chiral pool, using Garner's aldehyde 9 or by means of a radical cyclization on an L-serine derivative. 10 However, although they ensure a high optical purity of products, both routes suffer from a long synthetic sequence and a low overall yield.…”

Section: ■ Introductionmentioning

confidence: 99%

“…So far, amine 2 and its derivatives have been prepared by starting from the chiral pool, using Garner’s aldehyde or by means of a radical cyclization on an l -serine derivative . However, although they ensure a high optical purity of products, both routes suffer from a long synthetic sequence and a low overall yield.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Robalzotan, Ebalzotan, and Rotigotine Precursors via the Stereoselective Multienzymatic Cascade Reduction of α,β-Unsaturated Aldehydes

et al. 2013

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A stereoselective synthesis of bicyclic primary or secondary amines, based on tetralin or chroman structural moieties, is reported. These amines are precursors of important active pharmaceutical ingredients such as rotigotine (Neupro), robalzotan, and ebalzotan. The key step is based on a multienzymatic reduction of an α,β-unsaturated aldehyde or ketone to give the saturated primary or secondary alcohol, in a high yield and with a high ee. The catalytic system consists of the combination of an ene-reductase (ER; i.e., OYE2 or OYE3 belonging to the Old Yellow Enzyme family) with an alcohol dehydrogenase (ADH), applying the in situ substrate feeding product removal technology. By this system the formation of the allylic alcohol side product and the racemization of the chirally unstable α-substituted aldehyde intermediate are minimized. The primary alcohols were elaborated via a Curtius rearrangement. The combination of OYE2 with a Prelog or an anti-Prelog ADH allowed the preparation of the secondary alcohols with ee > 99% and de > 87%. The absolute configuration of the primary amines was unambiguously assigned by comparison with authentic samples. The stereochemistry of secondary alcohols was assigned by X-ray crystal structure and NMR analysis of Mosher esters.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Synthesis of Robalzotan, Ebalzotan, and Rotigotine Precursors via the Stereoselective Multienzymatic Cascade Reduction of α,β-Unsaturated Aldehydes

et al. 2013

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“… [17–21] However, limitations are also associated with these approaches, including sensitivity to moisture and the use of expensive non‐commercial chiral ligands [22, 23] . Other relevant, yet less effective approaches towards the synthesis of these moieties include the asymmetric aziridination of dihydronaphthalenes, [24] the organocatalytic reductive amination of 2‐tetralones, [25] and the radical cyclisation of substituted benzenes with l ‐serine derivatives [26, 27] …”

Section: Figurementioning

confidence: 99%

“…[22,23] Other relevant, yet less effective approaches towards the synthesis of these moieties include the asymmetric aziridination of dihydronaphthalenes, [24] the organocatalytic reductive amination of 2-tetralones, [25] and the radical cyclisation of substituted benzenes with l-serine derivatives. [26,27] Biocatalysts are increasingly highlighted as attractive tools for asymmetric synthesis due to their ability to achieve high levels of chemo-and enantioselectivity under mild conditions. [28] Biocatalytic synthesis of 2-aminotetralin and 3aminochroman derivatives has previously been studied with w-transaminases via the selective amination of tetralones [29,30] and chromanones.…”

Section: Chiralaminesoccupyaprominentroleduetotheirsyntheticmentioning

confidence: 99%

Synthesis of Pharmaceutically Relevant 2‐Aminotetralin and 3‐Aminochroman Derivatives via Enzymatic Reductive Amination

et al. 2021

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2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for > 15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinsons disease therapy Rotigotine in 63 % overall yield and 92 % ee.

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The Barton‐McCombie Reaction

2012

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Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site‐specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon‐centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C‐O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high‐yielding way to realize this sequence was first described by Barton McCombie using the free‐radical chain reaction of O ‐thioacyl derivatives of secondary alcohols with tri‐ n ‐butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products.

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Synthesis of enantiomerically pure 3-aminochroman derivatives

Cited by 14 publications

References 20 publications

Synthesis of Robalzotan, Ebalzotan, and Rotigotine Precursors via the Stereoselective Multienzymatic Cascade Reduction of α,β-Unsaturated Aldehydes

Synthesis of Robalzotan, Ebalzotan, and Rotigotine Precursors via the Stereoselective Multienzymatic Cascade Reduction of α,β-Unsaturated Aldehydes

Synthesis of Pharmaceutically Relevant 2‐Aminotetralin and 3‐Aminochroman Derivatives via Enzymatic Reductive Amination

The Barton‐McCombie Reaction

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