Synthesis of β-d-(1→4)-Substituted Trehalose Oligosaccharides

Abstract

Glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (5) with α-D-glucopyranosyl, α-maltosyl, and α-maltotriosyl bromides 4, 7, and 8 afforded the β-D-(1→4)-substituted trehalose tri-, tetra-, and pentasaccharides 6, 9, and 10 which were fully characterized by ¹H NMR spectroscopy. Deprotection gave the free oligosaccharides 1, 2, and 3.     

Regioselective Synthesis of β-D-Gal-(1→3)-D-Glcnac Using β-Galactosidase from Xanthomonas Manihotis

The carbohydrate chains of glycoconjugates are involved in a variety of molecular recognition events. For example, the tetrasaccharide sialyl Lewis a (sLe^a) plays a pivotal role in the metastasis of cancer cells.¹ In order to elucidate the biological tunction of carbohydrate chains, many researchers have synthesized components of carbohydrate chains. 2-Acetamido-2-deoxy-3-O-(β-D-galactopyranosyl)-D-glucopyranose (1) is an important constituent of sLe^a in complex type carbohydrate chains. This disaccharide has been synthesized using the transglycosylation activity of bovine testes β-galactosidase.² In this case the product mixtures contained unwanted isomers and had to be treated with Escherichia coli β-galactosidase in order to hydrolyze the undesired isomers. Eventually, 1 was obtained in 12 % yield. This methods is far from ideal as it requies two steps to obtain 1 and bovine testes are expensive and not easily available.     

The Synthesis of Four Dideoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract

Four derivatives of β-maltosyl-(1→4)-trehalose were prepared, each with two deoxy functions in one of the constitutive disaccharide building blocks. 2,3-Di-O-acetyl-4,6-dideoxy-4,6-diiodo-α-D-galactopyranosyl- (1→4) ?1,2,3,6-tetra-O-acetyl-D-glucopyranose (3) was employed as a precursor for the 4?,6?-dideoxygenated tetrasaccharide 9: coupling of 3 with 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzylidene-α-D-glucopyranoside (4) furnished the tetrasaccharide 5 which was deiodinated and deprotected to yield the target tetrasaccharide 9. Secondly, the dideoxygenated maltose derivative 3-deoxy-4,6-O-isopropylidene-2-O-pivaloyl-β-D-glucopyranosyl- (1→4) ?1,6-anhydro-3-deoxy-2-O-pivaloyl-β-D-glucopyranose (10) was ring-opened to the anomeric acetate 11. A [2+2] block synthesis with 4 in TMS triflate mediated glycosylation gave a tetrasaccharide which was deprotected to the 3″,3?-dideoxygenated analogue of β-maltosyl-(1→4)-trehalose. For the third tetrasaccharide, 2,3,2″,3′-tetra-O-benzyl-α,α-trehalose was iodinated at the primary positions and deiodinated in the presence of palladium-on-carbon, then this acceptor was selectively glycosylated with hepta-O-acetyl-maltosyl bromide (20). Removal of protective groups furnished the maltosyl trehalose tetrasaccharide deoxygenated at positions C-6 and C-6′. to prepare a 3,3′-dideoxygenated trehalose, the free hydroxyl groups of 2-O-benzyl-4,6-O-(R)-benzylidene-α-D-glucopyranosyl 2-O-benzyl-4,6-O-(R)-benzylidene-α-D-glucopyranoside (25) were reduced by Barton-McCombie deoxygenation. One of the benzylidene groups was opened reductively with sodium cyanoborohydride. The resulting free hydroxyl group at the 4′-position was glycosylated in a Koenigs-Knorr reaction with 20 to yield the 3,3′-dideoxygenated tetrasaccharide 32, the fourth target oligosaccharide, after deprotection.     

Synthesis of an antimetastatic tetrasaccharide β-D-Gal-(1→4)-β-d-GlcpNAc-(1→6)-α-D-Manp-(1→6)-β-D-Manp-OMe

An antimetastatic tetrasaccharide T₁,β-D-Gal-（1→4）-β-D-GlcpNAc-（1→6）-α-D-Manp-（1→6）-β-D-Manp-OMe,was synthesized with two approaches.The first approach was a conventional method employing thioglycoside and Koenigs-Knorr glycosylation reaction in 24%overall yield.The second one was a novel route through the azidoiodo-glycosylation strategy by using 2-iodo-2-deoxylactosyl azide as the donor in 36%overall yield.     

Synthesis of stigmasteryl (β1→4)-oligoglucosides

Stigmasteryl (β1→4)-oligoglucosides were prepared with cellobiose, cellotriose, and cellotetraose as glycan chains. For the preparation of the peracetylated oligoglucosyl donors anomeric acetate was deprotected and the respective hemiacetals were converted into trichloroacetimidates. Glycosylation with stigmasterol yielded both α- and β-anomers because during the treatment with Lewis acid the 2-OAc is cleaved to some extent; thus, with the emerging hydroxyl group neighboring group participation does not take place. Due to their different number of hydroxyl groups (0 vs. 1) separation of the two products proved to be facile. Saponification led to the desired stigmasteryl glucosides.     

Synthesis of 3-aminopropyl glycosides of branched β-(1→3)-glucooligosaccharides

Russian Chemical Bulletin - The synthesis of branched β-(1→3)-glucooligosaccharides bearing a β-d-glucose residue at position 6 of one of the monosaccharides of the linear chain at...     

The Synthesis of the 2- and 2′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose 1

Abstract

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2 or C-2′ have been synthesized in [2+2] block syntheses. N-Iodosuccinimide-mediated coupling of tetra-O-benzyl-glucose to tri-O-acetyl-D-glucal followed by O-acetylation furnished 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-α-D-mannopyranosyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside (7), which was used as a starting material for both tetrasaccharides. For the preparation of the 2′-monodeoxygenated saccharide the deoxyiodo pyranose moiety of 7 was further elaborated by de-O-acetylation, O-benzylidenation, O-benzylation, and selective reductive opening of the benzylidene acetal to give glycosyl acceptor 10. Glycosylation with hepta-O-acetylmaltosyl bromide and deprotection including removal of the iodo substituent afforded the 2′-deoxymaltosyl-(1→4)-trehalose 14. On the other hand, the non-iodinated pyranose moiety of 7 was transformed to a glycosyl acceptor. The removal of the benzyl groups of 7 necessitated also the reduction of the iodo group at this early stage. The resulting 3,4,6-tri-O-acetyl-2-deoxy-α-D-arabino-hexopyranosyl α-D-glucopyranoside was subjected to a similar reaction sequence as above to finally result in the 2-deoxymaltosyl-(1→4)-trehalose 22.

     

Synthesis of the fragment GlcNAc-α(1→p→6)-GlcNAc of the cell wall polymer of staphylococcus lactis having repeating N-acetyl-D-glucosamine phosphate units

The monofunctional phosphitylating reagents chloro-β-cyanoethyl-N,N-diisopropylamino-phosphoramidite ($\text{3}$) and salicylchlorophosphite ($\text{4}$) have been applied towards the introduction of an α(1→6) interglycosidic phosphodiester bond between two properly-protected N-acetyl-D-glucosamine units. Evidence will be presented to show that $\text{4}$ gives a higher yield of the required dimer than $\text{3}$.     

The Synthesis of the 2′′- and 2′′′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2′′ or C-2′′′ have been synthesized in [2+2] block syntheses. O-(2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-3,6-di-O-benzyl-1,2-di-O-acetyl-β-D-glucopyranose (6), prepared from the respective orthoester, was coupled to the glycosyl acceptor 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside. In the resulting tetrasaccharide 8, the only ester group was removed and replaced by a xanthate which was reduced in a Barton-McCombie reaction to afford the 2′′-deoxygenated tetrasaccharide 12. For the synthesis of a 2′′′-deoxygenated derivative, a maltose building block was assembled from two monosaccharides. The key building block was ethyl 2,3,6-tri-O-benzyl-1-thio-β-D-glucopyranoside (14) which was used i) as a glycosyl acceptor in a phenylselenyl chloride mediated coupling reaction with tri-O-benzyl-glucal and ii) after the first coupling as a glycosyl donor to react with glycosyl acceptor 7 to give tetrasaccharide 18. The phenylselenyl group was reduced with tributyltin hydride on the disaccharide level. Deprotection of 18 furnished the 2′′′-deoxy-maltosyl-(1→4)-trehalose 20.     

Synthesis of β-Nitroamines Using Nanocrystalline MgO

Nanocrystalline magnesium oxide (NAP-MgO) was found to be an effective heterogeneous, solid base catalyst for the direct aza-Henry reaction of nitroalkanes and various N-arylidene-4-methylbenzenesulfonamides to afford the corresponding β-nitroamines in excellent yields under mild conditions. The catalyst was recovered by simple centrifugation and reused for three cycles with consistent activity.      

Isolation of β-(1→4)-glucan synthetase from cottonplant shoots

An enzyme complex including -(14)-glucan synthetase has been isolated from cottonplant shoots by chromatography and electrophoresis. Accrding to electrophoretic analysis under denaturing conditions, the molecular masses of the polypeptides presumably present in in the glucan synthetase complex amounted to 74, 50, and 30 kDa.A. S. Sadykov Institute of Bioorganic Chemistry, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax 627071. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 87–90, January–February, 1994.     

Iodonium-Ion Assisted Stereospecific Glycosylation: Synthesis of Oligosaccharides Containing α(1-4)-Linked L-Fucopyranosyl Units

ABSTRACT

The terminal glycosyl acceptor methyl 2,3-di-O-benzyl-α-L-fucopyranoside (6) was extended three times with the non-terminal glycosyl donor ethyl 4-O-acetyl-2,3-di-O-benzyl-1-thio-ß-L-fucopyranoside (13) via iodonium-ion assisted glycosylations and intermittent removal of the C-4 acetyl group in intermediate dimer 16 and trimer 18. The 4-O-acetyl group in trimer 18 and tetramer 20 was highly resistant towards basic hydrolysis. The latter could be nullified by using dichloroacetyl instead of acetyl to protect the C-4-OH in the donor. The exclusive formation of 1,2-cis-linked oligomers could be explained by through-bond interactions exerted by the electron-withdrawing C-4 acyl group in the glycosyl donor.     

Dehydrocoupling Polymerization: Poly(silylether) Synthesis by Using an Iron β-Diketiminate Catalyst

We describe the iron-catalyzed polymerizations of diol and silane monomers to obtain fourteen different poly(silylether) products with number average molecular weights (M_n) up to 36.3 kDa. The polymerization reactions developed in this study are operationally simple and applicable to 1° and 2° silane monomer substrates and a range of benzylic and aliphatic diol substrates as well as one polyol example. The polymers were characterized by IR spectroscopy, DSC and TGA and, where solubility allowed, ¹H, ¹³C{¹H}, ²⁹Si{¹H} NMR spectroscopies, GPC and MALDI-TOF were also employed. The materials obtained displayed low T_g values (−70.6 to 19.1 °C) and were stable upon heating up to T_–5%,Ar 421.6 °C. A trend in T_–5%,Ar was observed whereby use of a 2° silane leads to higher T_–5%,Ar compared to those obtained using a 1° silane. Reaction monitoring was undertaken by in situ gas evolution studies coupled with GPC analysis to follow the progression of chain-length growth which confirmed a condensation polymerization-type mechanism.     

Synthetic α,β(1→4)-Glucan Oligosaccharides as Models for Heparan Sulfate

Abstract

α,β-(1→4)-Glucans were devised as models for heparan sulfate with the simplifying assumptions that carboxyl-reduction and sulfation of heparan sulfate does not decrease the SMC antiproliferative activity and that N-sulfates in glucosamines can be replaced by O-sulfates. The target oligo-saccharides were synthesized using maltosyl building blocks. Glycosylation of methyl 2,3,6,2′,3′,6′-hexa-O-benzyl-β-maltoside (1) with hepta-O-acetyl-α-maltosyl bromide (2) furnished tetrasaccharide 3 which was deprotected to α-D-Glc-(1→4)-β-D-Glc-(1→4)-α-D-Glc-(1→4)-β-D-Glc-(1→OCH₃) (5) or, alternatively, converted to the tetrasaccharide glycosyl acceptor (8) with one free hydroxyl function (4?′-OH). Further glycosylation with glucosyl or maltosyl bromide followed by deblocking gave the pentasaccharide [β-D-Glc-(1→4)-α-D-Glc-(1→4)]₂-β-D-Glc-(1→OCH₃) (11) and hexasaccharide [α-D-Glc-(1→4)-β-D-Glc-(1→4)₂-α-D-Glc-(1→4)-β-D-Glc-(1→OCH₃) (14). The protected tetrasaccharide 3 and hexasaccharide 12 were fully characterized by ¹H and ¹³C NMR spectroscopy. Assignments were possible using 1D TOCSY, T-ROESY, ¹H,¹H 2D COSY supplemented by ¹H-detected one-bond and multiple-bond ¹H,¹³C 2D COSY experiments.     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT

The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained upon selective iodination of a tetrasaccharide diol.     

Alumina Supported Synthesis of β-Lactams Using Microwave

N(4-hydroxycyclohexyl)-3-mercapto/cyano-4-arylazetidine-2-one were synthesised from N-(4-hydroxycyclohexyl)-arylaldimine by reacting with ethyl α-mercapto/α-cyanoacetate on basic alumina under microwaves, wherein not only the reaction time has been brought down from hours to minutes in comparison to conventional heating but also with improved yield.     

Synthesis of Epoxyalkyl (1→3)‐β‐D‐Oligoglucosides

Abstract

We describe an approach for the synthesis of (1→3)‐β‐D‐oligosaccharide derivatives 10–18. 1–9 were synthesized by treating peracetylated (1→3)‐β‐D‐oligosaccharides with the corresponding alkenyl alcohols and Lewis acid (SnCl₄) catalyst. Epoxidation of the corresponding alkenyl oligoglucosides took place by m‐CPBA. NaOMe in dry methanol was used for the deacetylation of the blocked derivatives, to give 10–18 in overall yields of 25–32%.     

Expedient Conversion of Lactose into Versatile Derivatives of Lactosamine and β-d-Galactosyl-(1→4)-d-mannosamine

Abstract

A practical, nine-step protocol is described for the preparation of synthetically useful N-acetyllactosamine (LacNAc) derivatives as well as LacNAc itself from lactose using the benzoylated oxime of lactos-2-ulosyl bromide 2 as the key intermediate. All steps are performed with simple reagents, do not require chromatography, are large-scale adaptable and allow overall yields of 30%.     

Solid-Phase Synthesis of Acrylamide Using Polymer-Supported β-Selenopropionic Acid

A novel polystyrene-supported β-selenopropionic acid has been developed and applied to facile synthesis of acrylamides.