A short and concise synthesis of isofagomine, homoisofagomine, and 5′-deoxyisofagomine

Ouchi, Hidekazu; Mihara, Yukiko; Watanabe, Hitomi; Takahata, Hiroki

doi:10.1016/j.tetlet.2004.07.127

Cited by 24 publications

(16 citation statements)

References 60 publications

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“…[11,[14][15][16][17][18][19] Importantly, generation of configurational diversity on the stereogenic centers appears to be of paramount importance to optimize their activity and selectivity. [20][21][22][23] Consequently, novel methodologies for the preparation of these compounds with a broad structural and configurational diversity are of increasing interest.…”

Section: Introductionmentioning

confidence: 99%

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

Calveras

Egido‐Gabás

Gómez

et al. 2009

Chemistry A European J

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The chemoenzymatic synthesis of a collection of pyrrolidine-type iminosugars generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C-alpha-substituted N-Cbz-2-aminoaldehydes derivatives, catalyzed by DHAP aldolases is reported. L-fuculose-1-phosphate aldolase (FucA) and L-rhamnulose-1-phosphate aldolase (RhuA) from E. coli were used as biocatalysts to generate configurational diversity on the iminosugars. Alkyl linear substitutions at C-alpha were well tolerated by FucA catalyst (i.e., 40-70 % conversions to aldol adduct), whereas no product was observed with C-alpha-alkyl branched substitutions, except for dimethyl and benzyl substitutions (20 %). RhuA was the most versatile biocatalyst: C-alpha-alkyl linear groups gave the highest conversions to aldol adducts (60-99 %), while the C-alpha-alkyl branched ones gave moderate to good conversions (50-80 %), with the exception of dimethyl and benzyl substituents (20 %). FucA was the most stereoselective biocatalyst (90-100 % anti (3R,4R) adduct). RhuA was highly stereoselective with (S)-N-Cbz-2-aminoaldehydes (90-100 % syn (i.e., 3R,4S) adduct), whereas those with R configuration gave mixtures of anti/syn adducts. For iPr and iBu substituents, RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high stereoselectivity. Molecular models of aldol products with iPr and iBu substituents and as complexes with the RhuA active site suggest that the anti adducts could be kinetically preferred, while the syn adducts would be the equilibrium products. The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of alpha-L-fucosidase (IC50=1-20 microM), moderate of alpha-L-rhamnosidase (IC50=7-150 microM), and weak of alpha-D-mannosidase (IC50=80-400 microM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were performed to understand both their binding capacity and the mode of interaction with the glycosidases.

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Section: Introductionmentioning

confidence: 99%

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

Calveras

Egido‐Gabás

Gómez

et al. 2009

Chemistry A European J

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“…Acetyl chloride (0.7 mL, 9.9 mmol) was dropwise added to a solution of 1a (760 mg, 3.0 mmol) and pyridine (0.96 mL, 11.2 mmol) in CH 2 Cl 2 (15 mL) with ice cooling and then the mixture was stirred at room temperature for 3 h. Ether was added to the mixture. The whole layer was washed with saturated NH 4 Cl and brine, dried over MgSO 4 , and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (n-hexane:AcOEt = 3:1) to give (AE )-6 as a yellow oil; yield: 888 mg (99 %).…”

Section: (Ae)-n-benzyloxycarbonyl-5-hydroxy-3-piperidene [(Ae )-1c]mentioning

confidence: 99%

“…over MgSO 4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (n-hexane:AcOEt = 2:1-1:1) to give (S)-2a (yield: 18 mg, 11 %, 36 % ee) and (R)-1 a (78 mg, 61 %, 91 % ee).…”

Section: Dedicated Cluster Full Papersmentioning

confidence: 99%

“…[3] We have previously reported on an efficient synthesis of 1-azasugars using N-protected 5-hydroxy-3-piperidene. [4] Several procedures are available for their racemic synthesis from readily available starting materials (pyridine, 3-hydroxypyridine and butadiene monoxide). Enantiopure forms can be produced by enzyme-mediated kinetic resolution, providing greater than 99 % ee.…”

Section: Introductionmentioning

confidence: 99%

“…[4] The regioselective opening of butadiene monoxide with allylamine, followed by protection (TsCl/NaHCO 3 , Boc 2 O/NaOH, CbzCl/ NaHCO 3 ) of the secondary amine gave the metathesis precursors 4, together with small amounts of regioisomers 5. Grubbs catalyst [9] could be used directly on 4 to afford the ring-closing metathesis products 1a-c in high yields.…”

Section: Introductionmentioning

confidence: 99%

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A New Preparation of Homochiral N‐Protected 5‐Hydroxy‐3‐ piperidenes, Promising Chiral Building Blocks, by Palladium‐ Catalyzed Deracemization of Their Alkyl Carbonates

et al. 2007

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Abstract:The palladium-catalyzed deracemization of N-protected alkyl carbonates of 5-hydroxy-3-piperidenes by use of chiral phosphine ligands is described. A Trost ligand such as (R)-BPA was found to be a suitable chiral ligand for the deracemization, providing N-protected 5-hydroxy-3-piperidenes in good yields with good to high enantioselectivities. A plausible mechanism for the reaction is proposed.

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Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A₁ and A₂ Stereoisomers

et al. 2007

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A novel straightforward chemoenzymatic procedure for the synthesis of hyacinthacine stereoisomers based on the aldol addition of dihydroxyacetone phosphate (DHAP) to N-Cbz-prolinal under catalysis by l-rhamnulose 1-phosphate aldolase from E. coli is presented. The synthesis is complemented by a simple and effective purification protocol consisting of ion-exchange chromatography on CM-sepharose. As examples, (À)-hyacinthacine A 2 [the enantiomer of (+)-hyacinthacine A 2 ], 7-deoxy-2-epialexine (the enantiomer of 3-epihyacinthacine A 2 ), ent-7-deoxyalexine (the enantiomer of 7-deoxyalexine) and 2-epihyacinthacine A 2 were synthesized by these procedures and characterized for the first time. These new isomers were assayed as inhibitors of glycosidases. As a result, (À)-hyacinthacine A 2 demonstrated to be a good inhibitor of a-d-glucosidase from rice whereas the natural enantiomer, hyacinthacine A 2 , was not. Moreover, a new family of inhibitors of a-l-rhamnosidase was uncovered.

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A short and concise synthesis of isofagomine, homoisofagomine, and 5′-deoxyisofagomine

Cited by 24 publications

References 60 publications

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

A New Preparation of Homochiral N‐Protected 5‐Hydroxy‐3‐ piperidenes, Promising Chiral Building Blocks, by Palladium‐ Catalyzed Deracemization of Their Alkyl Carbonates

Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A₁ and A₂ Stereoisomers

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A short and concise synthesis of isofagomine, homoisofagomine, and 5′-deoxyisofagomine

Cited by 24 publications

References 60 publications

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

A New Preparation of Homochiral N‐Protected 5‐Hydroxy‐3‐ piperidenes, Promising Chiral Building Blocks, by Palladium‐ Catalyzed Deracemization of Their Alkyl Carbonates

Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A1 and A2 Stereoisomers

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Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A₁ and A₂ Stereoisomers