Concepts for the Total Synthesis of Deoxy Sugars

Kirschning, Andreas; Jesberger, Martin; Schöning, Kai‐Uwe

doi:10.1055/s-2001-12342

Cited by 89 publications

(32 citation statements)

References 85 publications

(102 reference statements)

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“…[2] In particular, the enzymatic creation of deoxygenation sites is a most challenging step. [13] Chemical methods to prepare deoxysugars by total synthesis [14] or by regiospecific deoxygenation of natural Abstract: The majority of prokaryotic drugs are produced in glycosylated form, with the deoxygenation level in the sugar moiety having a profound influence on the drugs bioprofile. Chemical deoxygenation is challenging due to the need for tedious protective group manipulations.…”

Section: Introductionmentioning

confidence: 99%

Broadening Deoxysugar Glycodiversity: Natural and Engineered Transaldolases Unlock a Complementary Substrate Space

Rale

Schneider

Sprenger

et al. 2011

Chemistry A European J

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The majority of prokaryotic drugs are produced in glycosylated form, with the deoxygenation level in the sugar moiety having a profound influence on the drug's bioprofile. Chemical deoxygenation is challenging due to the need for tedious protective group manipulations. For a direct biocatalytic de novo generation of deoxysugars by carboligation, with regiocontrol over deoxygenation sites determined by the choice of enzyme and aldol components, we have investigated the substrate scope of the F178Y mutant of transaldolase B, TalB(F178Y), and fructose 6-phosphate aldolase, FSA, from E. coli against a panel of variously deoxygenated aldehydes and ketones as aldol acceptors and donors, respectively. Independent of substrate structure, both enzymes catalyze a stereospecific carboligation resulting in the D-threo configuration. In combination, these enzymes have allowed the preparation of a total of 22 out of 24 deoxygenated ketose-type products, many of which are inaccessible by available enzymes, from a [3×8] substrate matrix. Although aliphatic and hydroxylated aliphatic aldehydes were good substrates, D-lactaldehyde was found to be an inhibitor possibly as a consequence of inactive substrate binding to the catalytic Lys residue. A 1-hydroxy-2-alkanone moiety was identified as a common requirement for the donor substrate, whereas propanone and butanone were inactive. For reactions involving dihydroxypropanone, TalB(F178Y) proved to be the superior catalyst, whereas for reactions involving 1-hydroxybutanone, FSA is the only choice; for conversions using hydroxypropanone, both TalB(F178Y) and FSA are suitable. Structure-guided mutagenesis of Ser176 to Ala in the distant binding pocket of TalB(F178Y), in analogy with the FSA active site, further improved the acceptance of hydroxypropanone. Together, these catalysts are valuable new entries to an expanding toolbox of biocatalytic carboligation and complement each other well in their addressable constitutional space for the stereospecific preparation of deoxysugars.

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Section: Introductionmentioning

confidence: 99%

Broadening Deoxysugar Glycodiversity: Natural and Engineered Transaldolases Unlock a Complementary Substrate Space

Rale

Schneider

Sprenger

et al. 2011

Chemistry A European J

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“…[2 -7] Key features of our strategy are i) a selective O-allylation of the corresponding a-hydroxy carbonyl compound 1, ii) the diastereoselective addition of vinyl-or allylmetal compounds to the resulting O-allyl ethers 2, iii) the Ru-catalyzed ring closing metathesis of dienes 3, [8,9] which yields dihydropyrans (n ¼ 0) or oxepins (n ¼ 1) 4, respectively (Scheme 1). Oxacycles 4 have great potential in the de novo synthesis of carbohydrates or related compounds, [10,11] which has been demonstrated by us [5,12 -14] and others. [15 -19] Although apparently trivial, the first step of this sequence may cause significant problems.…”

Section: Introductionmentioning

confidence: 90%

Palladium‐Catalyzed O‐Allylation of α‐Hydroxy Carbonyl Compounds

Schmidt

Nave

2006

Adv Synth Catal

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“…However, chemical synthesis is in certain cases a useful alternative due to better opportunities for generalization. [6] Two examples for less common substitution patterns are 3-deoxygalactose (1) and 3-deoxyglucose (2) (Figure 1). Although they do not occur in nature, synthetic routes were investigated.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 3‐Deoxy Glycals via Tandem Metathesis Sequences and Their Use in an Intermolecular Heck Arylation

Schmidt

Biernat

2008

Eur J Org Chem

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Deoxy glycals can be synthesized from a mannitol-derived C 2 -symmetric diene diol by using the tandem RCM/isomerization approach. Incorporation of a ruthenium-catalyzed dehydrogenative silylation step into the reaction sequence is possible. Thus, an orthogonally protected 3-deoxy glycal results via a tandem RCM/hydrosilylation/isomerization sequence. All ruthenium-catalyzed steps of this tandem se-

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Concepts for the Total Synthesis of Deoxy Sugars

Abstract: Total synthesis concepts for the preparation of deoxygenated hexoses which are constituents of many secondary metabolites with antibacterial and antitumor activity are surveyed.

Cited by 89 publications

References 85 publications

Broadening Deoxysugar Glycodiversity: Natural and Engineered Transaldolases Unlock a Complementary Substrate Space

Broadening Deoxysugar Glycodiversity: Natural and Engineered Transaldolases Unlock a Complementary Substrate Space

Palladium‐Catalyzed O‐Allylation of α‐Hydroxy Carbonyl Compounds

Synthesis of 3‐Deoxy Glycals via Tandem Metathesis Sequences and Their Use in an Intermolecular Heck Arylation

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