Highly Regio- and Enantioselective Reduction of 3,5-Dioxocarboxylates

Wolberg, Michael; Hummel, Werner; Wandrey, Christian; Müller, Michael

doi:10.1002/1521-3773(20001201)39:23<4306::aid-anie4306>3.0.co;2-g

Cited by 143 publications

(62 citation statements)

References 19 publications

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“…droxy-6-methylbenzoate, [12] methyl 2-hydroxy-4-methoxy-6-methylbenzoate, [13] 5, [15] (R)-6 [14] and (S)-6 [17] were synthesized according to published procedures. TLC was carried out on aluminium sheets precoated with silica gel 60F 254 (Merck).…”

Section: Methodssupporting

confidence: 51%

“…For the synthesis of (R)-4, a method developed by Wolberg et al [14] was used. The regio-and stereoselective enzymatic reduction of tert-butyl 3,5-dioxohexanoate (5) [15] with alcoholdehydrogenase from Lactobacillus brevis (LBADH) afforded almost optically pure (R)-6 (99.4% ee) in high yield.…”

Section: Synthesis Of the Chiral Michael Acceptorsmentioning

confidence: 99%

“…To a stirred solution of (R)-6 [14] (500 mg, 2.48 mmol) in dry dichloromethane (40 mL) at 0°C was added trifluoroacetic acid (0. …”

Section: (R)-56-dihydro-4-hydroxy-6-methyl-2h-pyran-2-one [(R)-7]mentioning

confidence: 99%

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Total Synthesis of (R)- and (S)-semi-Vioxanthin

Drochner

Müller

2001

Eur. J. Org. Chem.

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Section: Methodssupporting

confidence: 51%

Section: Synthesis Of the Chiral Michael Acceptorsmentioning

confidence: 99%

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Total Synthesis of (R)- and (S)-semi-Vioxanthin

Drochner

Müller

2001

Eur. J. Org. Chem.

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“…another from Lactobacillus brevis (LBADH) 14 have shown excellent stereoselectivities towards the reduction of, e.g. -azido ketones 15 and -alkyl--keto esters, 16 and more importantly, with opposite stereopreference.…”

Section: Methodsmentioning

confidence: 99%

Highly enantioselective synthesis of α-azido-β-hydroxy methyl ketones catalyzed by a cooperative proline–guanidinium salt system

et al. 2014

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COMMUNICATIONThis journal is © The Royal Society of Chemistry 2012 J. Name., 2012, 00, 1-3 | 1 are typically accessed by a base-promoted aldol reaction of an -azidoketone 2 and a non-enolizable aldehyde 3 3 (Scheme 1). Scheme 1Although these protocols render the aldol aducts 1 with optimum chemical yield, undesired mixtures of anti and syn isomers are always present. In fact, to our knowledge, there are no methodologies described in the literature that allow gaining access to -azido--hydroxy ketones 1 in a controlled diastereo-and enantioselective manner. Proline is the most popular organocatalyst. This naturally occurring amino acid is cheap, readily available in both enantiomeric forms, and can be used for a wide range of synthetic transformations. 6 Aiming to avoid the use of other synthetically elaborated organocatalysts, our group, 4 and others, 7 have demonstrated how the addition of additives can enhance the reactivity and selectivity of this off-the-bench catalyst in classical transformations such as the aldol reaction. Moreover, the addition of additives can also expand the boundaries of proline as catalyst. In this sense, we have reported the first proline-catalyzed asymmetric synthesis of chlorohydrins through the intermolecular aldol reaction between chloroacetone and aromatic aldehydes, made feasible by the participation of a guanidinium salt as an additive. Motivated by our previous results, we decided to explore the behaviour of our catalytic guanidinium salt/proline system towards a reaction like that illustrated in Scheme 1. 4-Nitrobenzaldehyde, 4a, was adopted as the model substrate for preliminary reactions. Azidoacetone (5, 1-azidopropan-2-one) was prepared in multi-gram scale, in 96% yield, from chloroacetone and sodium azide. In correspondence with our previous work, we decided to evade the use of any organic solvent, apart from ketone 5, which acts as both reagent and reaction media.8 A careful optimization of the stoichiometries involved in the reaction, time, temperature, as well as the judicious choice of the anion accompanying the guanidinium salt, revealed ideal conditions (see Supporting Information (SI) for details, Tables S1-S5). So, when a suspension of (S)-proline (10 mol%), guanidinium salt 6 (15 mol%) and 4-nitrobenzaldehyde 4a, in a moderate excess of azidoacetone 5

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“…Enantiomerically pure alcohols, which cannot be produced by chemical synthesis, can be synthesized by biocatalysts such as alcohol dehydrogenases (ADH), which react stereospecifically (Hummel 1990;Leuchs and Greiner 2011;Wolberg et al 2000;Daußmann et al 2006;Rosen et al 2004). The easiest and oldest method for producing ADHs is through the use of wild-type cells of an organism producing it innately.…”

Section: Introductionmentioning

confidence: 99%

Coexpression of Lactobacillus brevis ADH with GDH or G6PDH in Arxula adeninivorans for the synthesis of 1-(R)-phenylethanol

Rauter¹,

Prokoph

Kasprzak

et al. 2014

Appl Microbiol Biotechnol

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The yeast Arxula adeninivorans was used for the overexpression of an ADH gene of Lactobacillus brevis coding for (R)-specific alcohol dehydrogenase (LbADH) to synthesise enantiomerically pure 1-(R)-phenylethanol. Glucose dehydrogenase gene from Bacillus megaterium (BmGDH) or glucose 6-phosphate dehydrogenase of Bacillus pumilus (BpG6PDH) were coexpressed in Arxula to regenerate the cofactor NADPH by oxidising glucose or glucose 6-phosphate. The yeast strain expressing LbADH and BpG6PDH produced 5200 U l(-1) ADH and 370 U l(-1) G6PDH activity, whereas the strain expressing LbADH and BmGDH produced 2700 U l(-1) ADH and 170 U l(-1) GDH activity. However, the crude extract of both strains reduced 40 mM acetophenone to pure 1-(R)-phenylethanol with an enantiomeric excess (ee) of >99 % in 60 min without detectable by-products. An increase in yield was achieved using immobilised crude extracts (IEs), Triton X-100 permeabilised cells (PCs) and permeabilised immobilised cells (PICs) with PICs being most stable with GDH regeneration over 52 cycles. Even though the activity and synthesis rate of 1-(R)-phenylethanol with the BpG6PDH and LbADH coexpressing strain was higher, the BmGDH-LbADH strain was more stable over successive reaction cycles. This, combined with its higher total turnover number (TTN) of 391 mol product per mole NADP(+), makes it the preferred strain for continuous reaction systems. The initial non-optimised semi-continuous reaction produced 9.74 g l(-1) day(-1) or 406 g kg(-1) dry cell weight (dcw) day(-1) isolated 1-(R)-phenylethanol with an ee of 100 % and a TTN of 206 mol product per mole NADP(+). In conclusion, A. adeninivorans is a promising host for LbADH and BpG6PDH or BmGDH production and offers a simple method for the production of enantiomerically pure alcohols.

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Highly Regio- and Enantioselective Reduction of 3,5-Dioxocarboxylates

Cited by 143 publications

References 19 publications

Total Synthesis of (R)- and (S)-semi-Vioxanthin

Total Synthesis of (R)- and (S)-semi-Vioxanthin

Highly enantioselective synthesis of α-azido-β-hydroxy methyl ketones catalyzed by a cooperative proline–guanidinium salt system

Coexpression of Lactobacillus brevis ADH with GDH or G6PDH in Arxula adeninivorans for the synthesis of 1-(R)-phenylethanol

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