Chemoenzymatic Synthesis of Enantiomerically Pure (2S,3R,4S)‐4‐Hydroxyisoleucine, an Insulinotropic Amino Acid Isolated from Fenugreek Seeds

Rolland-Fulcrand, Valérie; Rolland, Marc; Roumestant, M. L.; Martinez, Jean

doi:10.1002/ejoc.200300434

Cited by 23 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several methods of chemo enzymatic synthesis of HIL have been reported. Wang Q. et al reported an eight-step synthesis process involving a stereoselective bioreduction step catalyzed by Geotrichum candidum (Wang et al 2002), and Rolland-Fulcrand V. et al reported a six-step synthesis process involving an enzymatic chiral resolution step catalyzed by immobilized penicillin acylase G (Rolland-Fulcrand et al 2004).…”

Section: Introductionmentioning

confidence: 99%

A novel l-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid

Ogawa

Kodera

Smirnov

et al. 2010

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

4-Hydroxyisoleucine (HIL) found in fenugreek seeds has insulinotropic and anti-obesity effects and is expected to be a novel orally active drug for insulin-independent diabetes. Here, we show that the newly isolated strain Bacillus thuringiensis 2e2 and the closely related strain B. thuringiensis ATCC 35646 operate a novel metabolic pathway for L-isoleucine (L-Ile) via HIL and 2-amino-3-methyl-4-ketopentanoic acid (AMKP). The HIL synthesis was catalyzed stereoselectively by an α-ketoglutaric acid-dependent dioxygenase and to be useful for efficient production of a naturally occurring HIL isomer, (2S,3R,4S)-HIL. The (2S,3R,4S)-HIL was oxidized to (2S,3R)-AMKP by a NAD(+)-dependent dehydrogenase. The metabolic pathway functions as an effective bypass pathway that compensates for the incomplete tricarboxylic acid (TCA) cycle in Bacillus species and also explains how AMKP, a vitamin B(12) antimetabolite with antibiotic activity, is synthesized. These novel findings pave a new way for the commercial production of HIL and also for AMKP.

show abstract

Section: Introductionmentioning

confidence: 99%

A novel l-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid

Ogawa

Kodera

Smirnov

et al. 2010

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…This decrease in rate may well be due to the increase in sterics in the proximity of the double bond; in the pseudoequatorial conformer (the more stable one), the methyl indeed hinders one face of the double bond, whereas the tosyl group hinders the other one (see Figure 3 for the structure of 4, which is closely related to 14). Finally, in a desire to explore the development of new compounds with antidiabetic properties and structurally related to 4-hydroxyisoleucine, [14] we envisaged the conversion of the protected amino alcohol 14 into the protected γ-hydroxy-α-amino acid 15 (Scheme 6). Thus, an oxidative www.eurjoc.orgcleavage of the terminal double bond of 14, followed by the esterification of the corresponding carboxylic acid, led to the protected γ-hydroxy-α-amino acid 15 in a (nonoptimized) yield of 50 %.…”

Section: Resultsmentioning

confidence: 99%

A Stereoselective Approach to 1,3‐Amino Alcohols Protected as Cyclic Carbamates: Kinetic vs. Thermodynamic Control

Broustal¹,

Ariza²,

Campagne³

et al. 2007

Eur J Org Chem

View full text Add to dashboard Cite

International audienceDirect enantiocontrolled access to 1,3-amino alcohols protected as cyclic carbamates is described. The approach is based on the addition of a silyl dienolate to aldehydes in the presence of 10 % of Carreira's catalyst (vinylogous Mukaiyama-aldol addition). The obtained -hydroxyesters were reduced to pent-2-ene-1,5-diols, which were converted into the corresponding dicarbamates with tosyl isocyanate. Stereoselective cyclization of these dicarbamates proceeded with 1,3-asymmetric induction under either thermodynamic or kinetic control to afford enantioselectively six-membered-ring cyclic carbamates. Calculations enabled us to rationalize the observed stereoselectivit

show abstract

“…This ratio was deduced from a comparison of the integrals of the 1 H NMR resonances of 4-H (δ = 4.81 ppm, integral = 0.03 for cis-15; δ = 4.57 ppm, integral = 1.00 for trans -15). (Attempts to achieve purifi-NaHCO 3 (18), KCl (4.7), CaCl 2 (2.5), MgSO 4 ·7H 2 O (1.2), KH 2 PO 4 (1.2) and supplemented with 8.3 m glucose and 2 g/L bovine serum albumin. The pH of the medium was adjusted to 7.4 by bubbling through a mixture of O 2 /CO 2 (95:5).…”

Section: 6-dideoxy-3-o-methyl-d-xylo-hexono-14-lactone (8b)mentioning

confidence: 99%

Multi‐Step Synthesis and Biological Evaluation of Analogues of Insulin Secretagogue (2S,3R,4S)‐4‐Hydroxyisoleucine

Lajoix¹,

Gross²,

Praly³

2008

Eur J Org Chem

View full text Add to dashboard Cite

A series of stereochemically defined analogues of (2S,3R,4S)‐4‐hydroxyisoleucine and related α‐hydroxy acids have been prepared by multi‐step routes from D‐glucose, whereas ketolization between TBDMS‐protected hydroxypropanone and ethyl isocyanoacetate led to racemic analogues. Bioassays showed that of eight newly synthesized compounds, two of them presented an interesting statistical trend to increase glucose‐induced insulin secretion when tested in isolated rat pancreatic islets in the presence of 8.3 mM glucose and at a concentration of 200 μM, which has previously been shown to be effective for (2S,3R,4S)‐4‐hydroxyisoleucine.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

show abstract

Chemoenzymatic Synthesis of Enantiomerically Pure (2S,3R,4S)‐4‐Hydroxyisoleucine, an Insulinotropic Amino Acid Isolated from Fenugreek Seeds

Cited by 23 publications

References 19 publications

A novel l-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid

A novel l-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid

A Stereoselective Approach to 1,3‐Amino Alcohols Protected as Cyclic Carbamates: Kinetic vs. Thermodynamic Control

Multi‐Step Synthesis and Biological Evaluation of Analogues of Insulin Secretagogue (2S,3R,4S)‐4‐Hydroxyisoleucine

Contact Info

Product

Resources

About