Casuarine Stereoisomers from Achiral Substrates: Chemoenzymatic Synthesis and Inhibitory Properties

Concia, Alda Lisa; Gómez, Livia; Parella, Teodor; Joglar, Jesús; Clapés, Pere

doi:10.1021/jo500991p

Cited by 18 publications

(6 citation statements)

References 29 publications

(54 reference statements)

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“…Apart from the “Izumoring strategy”, aldol additions catalyzed by aldolases afford a promising alternative for rare sugar synthesis through joining two smaller fragments. − Among all aldolases, the dihydroxyacetone phosphate (DHAP)-dependent aldolases are very popularly used for building carbon–carbon bonds in synthesizing carbohydrates and their derivatives. − In our previous study, we adopted a one-pot four-enzyme system based on different DHAP-dependent aldolases and successfully used it to produce various rare ketoses. − In this system (Scheme ), we had to supply both fragments for the aldol reaction: glycerol 3-phosphate was used to produce DHAP through oxidation by glycerol phosphate oxidase (GPO), whereas the acceptor aldehyde had to be added externally. The by-product hydrogen peroxide from the oxidation step must be degraded into oxygen and water by catalase.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Multienzyme Synthesis of Rare Ketoses from Glycerol

Cai

et al. 2020

J. Agric. Food Chem.

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A facile approach is introduced here for the synthesis of rare ketoses from glycerol and d-/l-glyceraldehyde (d-/l-GA). The reactions were carried out in a one-pot multienzyme fashion in which the only carbon source is glycerol. In the enzymatic cascade, glycerol is phosphorylated and then oxidized at C2 to afford dihydroxyacetone phosphate (DHAP), the key donor for enzymatic aldol reaction. Meanwhile, the primary alcohol of glycerol is also oxidized to give the acceptor molecule GA in situ (d- or l-isomer could be formed stereospecifically with either alditol oxidase or horse liver alcohol dehydrogenase). Different DHAP-dependent aldolases were used to generate the aldol adducts (rare ketohexose phosphates) with various stereoconfigurations and diastereomeric ratios. It is worth noting that the enzyme that catalyzes the phosphorylation reaction in the first step could also help recycle the phosphate in the last step to provide free rare sugar molecules. This study provides a useful method for rare ketose synthesis on a 100 mg to g scale, starting from relatively inexpensive materials which solved the problem of supplying both glycerol 3-phosphate and GA in our previous work. It also demonstrates an example of green synthesis due to highly efficient carbon usage and recycling of cofactors.

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Section: Introductionmentioning

confidence: 99%

One-Pot Multienzyme Synthesis of Rare Ketoses from Glycerol

Cai

et al. 2020

J. Agric. Food Chem.

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“…These wild-type or variant (FucA F131A ) aldolases have shown a broad tolerance towards acceptor substrates, even accepting in some cases sterically constrained aldehydes. [6][7][8] The strict requirement for the donor substrate DHAP, a rather expensive and unstable compound has led to the development of various strategies for its synthesis. Thus, well documented chemical or enzymatic DHAP preparations are accessible [9] and have facilitated the use of DHAP-dependent aldolases in organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

l-Rhamnulose-1-phosphate and l-fuculose-1-phosphate aldolase mediated multi-enzyme cascade systems for nitrocyclitol synthesis

Bres¹,

Guérard-Hélaine²,

Hélaine³

et al. 2015

Journal of Molecular Catalysis B: Enzymatic

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One-pot multistep stereoselective cascade reactions were implemented for the straightforward synthesis of various nitrocyclitols. Two kinases, an aldolase and a phosphatase were involved in this process together with a spontaneous intramolecular Henry reaction to provide a nitrocyclitol moiety. The C-C bond formation catalyzed by the aldolase and the nitroaldol reaction were key steps to build the carbocycle stereoselectively. The acceptor substrates for aldolases were all 4-nitrobutanal structurally based, hydroxylated or not on C2 and/or C3 positions. On the one side, L-fuculose-1-phosphate aldolase (FucA) has catalyzed the formation of the expected (R,R; D-erythro) aldol except in the case of 4-nitrobutanal from which (R,S; L-threo) aldol was also present. On the other side, L-rhamnulose-1-phosphate aldolase has always provided the expected (R,S; L-threo) aldol together with minor amount of (R,R; D-erythro) aldol thus being less stereoselective than FucA. The intramolecular Henry reaction has occurred spontaneously on the aldol due to the presence of both ketone and terminally positioned nitro group. This cyclisation was stereoselective and correlated to the presence or not of a hydroxyl group in β to the nitro group. From 4-nitrobutanal as substrate and for one defined stereochemistry by the aldolase (R,R or R,S) one cyclitol was formed. In the other cases, two diastereomeric series were formed due to the presence of an R and S configured alcohol function in β to the nitro group. The combination of this set of reactions successfully furnished 11 nitrocyclitols never described before in literature.

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“…In the second study, a related 'double aldol' approach gave access to four stereoisomers of the polyhydroxylated pyrrolizidine alkaloid casuarine. 139 The aldol addition of dihydroxyacetone (241) to aldehyde 256, catalysed either by FSA variant A129S-A165G or by RhuA, and followed by hydrogenation, Cbz protection, and oxidation, yielded aldehyde 257 and its enantiomer, as described in a previous study (Scheme 32). 140 The two aldehydes 257 and ent-257 were coupled with dihydroxyacetone phosphate by FucA variant F131A with (R)-selectivity at the 2 0 carbon atom, irrespective of the aldehyde stereochemistry.…”

Section: Aldolasesmentioning

confidence: 96%