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Showing papers on "Glycal published in 2017"


Journal ArticleDOI
TL;DR: In this article, a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles was described.
Abstract: Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd2(dba)3 (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the β-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the β-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.

83 citations


Journal ArticleDOI
TL;DR: Mechanistic investigations suggest that the reaction proceeds via Au(I)-catalyzed hydrofunctionalization of the enol ether glycoside.
Abstract: Au(I) in combination with AgOTf enables the unprecedented direct and α-stereoselective catalytic synthesis of deoxyglycosides from glycals. Mechanistic investigations suggest that the reaction proceeds via Au(I)-catalyzed hydrofunctionalization of the enol ether glycoside. The room temperature reaction is high yielding and amenable to a wide range of glycal donors and OH nucleophiles.

70 citations


Journal ArticleDOI
TL;DR: Palladium(II) in combination with a monodentate phosphine ligand enables the unprecedented direct and α‐stereoselective catalytic synthesis of deoxyglycosides from glycals.
Abstract: Palladium(II) in combination with a monodentate phosphine ligand enables the unprecedented direct and α-stereoselective catalytic synthesis of deoxyglycosides from glycals. Initial mechanistic studies suggest that in the presence of N-phenyl-2-(di-tert-butylphosphino)pyrrole as the ligand, the reaction proceeds via an alkoxy palladium intermediate that increases the proton acidity and oxygen nucleophilicity of the alcohol. The method is demonstrated with a wide range of glycal donors and acceptors, including substrates bearing alkene functionalities.

54 citations


Journal ArticleDOI
TL;DR: In this paper, the authors achieved stereoselective construction of various O-glycosidic bonds with different palladium sources using 3,4-O-carbonate galactal as the donor to reach yields up to 95% under mild conditions.
Abstract: Stereoselective construction of various O-glycosidic bonds was first achieved by different palladium sources using 3,4-O-carbonate galactal as the donor to reach yields up to 95% under mild conditions. With Pd(II) catalyst coordination of this glycal donor from the β-face directed by carbonate group, hard nucleophiles (aliphatic alcohols) gave β-glycosides and α-glycosides were obtained from soft nucleophiles (phenols). In contrast, with the Pd(0) catalyst coordinating the donor from the β-face due to steric effect, both hard and soft acceptors could only generate β-glycosides via hydrogen-bond-mediated aglycone delivery.

31 citations


Journal ArticleDOI
TL;DR: In this paper, a method to obtain enantiomerically pure 8-oxabicyclo[3.2.1] octanes via gold-catalyzed tandem 1,3-acyloxy migration/Ferrier rearrangement of glycal derived 1,6-enyne bearing propargylic carboxylates is described.
Abstract: Herein, we describe an efficient method to prepare enantiomerically pure 8-oxabicyclo[3.2.1]octanes via gold(I)-catalyzed tandem 1,3-acyloxy migration/Ferrier rearrangement of glycal derived 1,6-enyne bearing propargylic carboxylates. The resultant compounds could then undergo interrupted Nazarov cyclization to afford diastereomerically pure 11-oxatricyclo[5.3.1.0]undecanes.

20 citations


Journal ArticleDOI
TL;DR: The pyranose members of the pyrrolomorpholine spiroketal family have been synthesized by stereoselective spirocyclizations of a common glycal precursor, leading to the identification of novel 2-hydroxy analogues with more potent antioxidant activities than the natural products.
Abstract: The pyranose spiroketal natural products pollenopyrroside A and shensongine A (also known as xylapyrroside A, ent-capparisine B) have been synthesized by stereoselective spirocyclizations of a common C1-functionalized glycal precursor. In conjunction with our previously reported syntheses of the corresponding furanose isomers, this provides a versatile family-level synthesis of the pyrrolomorpholine spiroketal natural products and analogues. In rat mesangial cells, hyperglycemia-induced production of reactive oxygen species, which is implicated in diabetic nephropathy, was inhibited by pollenopyrroside A and shensongine A with mid-μM IC50 values, while unnatural C2-hydroxy analogues exhibited more potent, sub-μM activity.

12 citations


Journal ArticleDOI
TL;DR: Pd-catalyzed regio- and stereoselective C-nucleoside synthesis from pyranoid glycals and unactivated N,N-dialkyluracils is described, which obviates the use of heavy metals such as mercury or preactivation of protected uracils, making it an attractive strategy for C- nucleosides synthesis.

11 citations


Journal ArticleDOI
TL;DR: It was found that sugar-derived thiocyanate was a better electrophile than corresponding asymmetric disulfide in this type of stereoselective sulfenylation.

7 citations



Journal ArticleDOI
TL;DR: The stereochemical course of O-glycosidation of 1,2-α-d-anhydrosugars (glycal epoxides) with phenols can be tuned by varying the metal ion of the base to obtain mixture of the anomers.

4 citations


Journal ArticleDOI
TL;DR: In this article, a new protocol for the synthesis of d -galactal-derived N -ethoxycarbonyl vinyl aziridine 1β-CO 2 Et, starting from tri-O -acetyl- d -glucal, is described.

Journal ArticleDOI
TL;DR: Two efficient, metal free reagent systems for stereoselective synthesis of trans -2-deoxy-2-iodoglycosylacetates and O -iodobenzoates respectively from differently protected glycals have been developed and are compatible with a variety of protecting groups and various functional groups at 2 C -position.

Journal ArticleDOI
TL;DR: A series of 1,5-anhydro- d - glycero - d - gluco -heptitol derivatives have been prepared from 3- O -benzyl-1,2- O-isopropylidene via conversion into anomeric bromide and thiophenyl derivatives, followed by glycal formation and reductive desulfurization, respectively.
Abstract: A series of 1,5-anhydro- d - glycero - d - gluco -heptitol derivatives have been prepared from 3- O -benzyl-1,2- O -isopropylidene- d - glycero - d - gluco -heptofuranose via conversion into anomeric bromide and thiophenyl derivatives, followed by glycal formation and reductive desulfurization, respectively. Global deprotection of the protected intermediates afforded the 1,5-anhydro derivatives of the d - glycero - d - gluco - and 1,2-dideoxy- d - altro - configuration as well as the 1,5-anhydro-2-deoxy- d - altro -hept-1-enitol. In addition, the 7- O -phosphorylated d - glycero - d - gluco -heptose and its 1,5-anhydro analogue were prepared in good yields utilizing phosphoramidite chemistry. A novel heptitol analogue based on a 1-deoxynojirimycin scaffold was also elaborated via a Wittig­-type chain elongation followed by dihydroxylation, separation of the resulting epimers, and global deprotection. The target compounds, however, were not active as inhibitors of the bacterial sedoheptulose-7-phosphate isomerase GmhA.

Journal ArticleDOI
TL;DR: The subsequent chemoselective removal of the protecting group at O-6 of two GlcNAcs, sulfation, and deprotection procedures as well as biotinylation gave the target compound.

Journal ArticleDOI
01 Oct 2017-Synlett
TL;DR: The catalyst-free addition of organozinc species to glycal derivatives and dihydropyrans in a toluene/ n -dibutyl ether solvent mixture via a Ferrier rearrangement at room temperature requires only a slight excess of the nucleophile and leads preferentially to the C-glycoside α-anomer.
Abstract: Herein, we report the catalyst-free addition of organozinc species to glycal derivatives and dihydropyrans in a toluene/ n -dibutyl ether solvent mixture via a Ferrier rearrangement at room temperature. This methodology requires only a slight excess of the nucleophile and leads preferentially to the C-glycoside α-anomer. Various 1,2-dihydropyrans were assessed with a range of nucleophiles (aryl, alkynyl, alkyl) yielding the desired C -glycosides in good yield and diastereoselectivity up to 20:1.

Patent
24 May 2017
TL;DR: In this article, a simple and easy-to-operate glycal preparation method is presented, which is low-cost and environment-friendly, and has market advantages, while yield of glycal prepared by the method is good.
Abstract: The invention belongs to the technical field of chemical engineering and discloses a preparation method of glycal. The method comprises the following steps: (1) adding an organic solvent into a reactor equipped with polyhydroxyaldehyde monosaccharide and a catalyst in an atmosphere of nitrogen, adding a hydroxyl protective agent, carrying out a reflux reaction, and carrying out subsequent processing to obtain a compound a; (2) successively adding ammonium salt and an organic solvent into the compound a under the condition of nitrogen so as to carry out a reaction, and carrying out subsequent processing to obtain a compound b; (3) letting the compound b, substituted hydrazine and a water-removal additive into an organic solvent under the condition of nitrogen so as to carry out a reaction, and carrying out subsequent processing to obtain a compound c; and (4) adding a catalyst and the compound c dissolved in the organic solvent into alkali under the condition of nitrogen, reacting, and carrying out subsequent processing so as to obtain glycal. The preparation method is simple and easy to operate, is low-cost and environment-friendly, and has market advantages. Meanwhile, yield of glycal prepared by the preparation method is good.

Patent
03 Nov 2017
TL;DR: In this paper, a synergistic bactericide composition consisting of polyoxins and glucan glycal was proposed for preventing and treating alternaria leaf spot of apple trees and the like.
Abstract: The invention provides a synergistic bactericide composition, and a preparation method and application thereof The effective medicinal components of the composition consist of polyoxins and glucan glycal, wherein the weight ratio of the polyoxins to the glucan glycal is (5-10):(01-5); the synergistic bactericide composition is prepared by a mixing mode and can be applied to preparation of pesticide for preventing and treating alternaria leaf spot; and the polyoxins and the glucan glycal in the composition are compounded according to the specific proportion and are synergistic, so the effect of preventing and treating alternaria leaf spot of apple trees and the like is remarkable