Showing papers on "Glycal published in 2005"

Stereocontrolled synthesis of spiroketals via a remarkable methanol-induced kinetic spirocyclization reaction.

Abstract: A methanol-induced kinetic spiroketalization reaction has been developed for the stereocontrolled target- and diversity-oriented synthesis of spiroketals. In contrast to existing methods for spiroketal synthesis, this reaction does not depend on thermodynamic product stability or require axial attack of an oxygen nucleophile. Stereodiverse glycals are alkylated at the C1 position with side chains bearing protected hydroxyl groups. After alcohol deprotection, the glycal is epoxidized stereoselectively, then the side chain hydroxyl is spirocyclized with inversion of configuration at the anomeric carbon by addition of excess MeOH at -63 degrees C. This spirocyclization reaction appears to proceed by MeOH hydrogen-bonding catalysis and has been used to form five- and six-membered rings with stereoisomeric substituents. In some cases, the stereocomplementary spiroketals can be also obtained by classical acid-catalyzed equilibration.

exo-Glycal Chemistry: General Aspects and Synthetic Applications for Biochemical Use

Abstract: It is well known that carbohydrates play an indispensable role in a variety of essential biological activities, such as cell-cell adhesion, bacteria and virus infections, and tumor metastasis. Among an increasing number of sugars and sugar mimetics that have been designed and synthesized for the purpose of drug discovery, C-glycosides are considered to be one of the best choices on account of their stability and resemblance as they differ from normal glycosides only in glycosidic linkages. exo-Glycals are unsaturated sugars that have a double bond attached to the anomeric center outside the sugar ring. These carbohydrate molecules are useful for the synthesis of C-glycosides and compounds containing quaternary carbons, provided that the olefin can be properly reduced or functionalized. This review places special emphasis on two aspects of exo-glycals including general methods of preparation and synthetic applications for making biologically important molecules. The first half discusses the methods of addition/elimination and Ramburg-Backlund rearrangement that offer many beneficial features including a wide range of double bond substitutions, limited reaction steps, easy operation and good overall yields. The rest of the article demonstrates a number of synthetic studies using exoglycals as the starting materials. The target molecules can be categorized into three groups, namely C-glycosides, enzyme inhibitors and bioactive natural products.

Enantioselective synthesis of erythro-4-deoxyglycals as scaffolds for target- and diversity-oriented synthesis: new insights into glycal reactivity.

Abstract: An efficient, enantioselective synthesis of erythro-4-deoxyglycals has been developed using asymmetric aldehyde allylation and tungsten-catalyzed alkynol endo-cycloisomerization as the key steps. These versatile synthetic scaffolds have been elaborated to a variety of products using stereoselective transformations that are complementary to those available using the corresponding threo glycals. This work has provided valuable insights into the relationships between glycal structure and reactivity. In addition, a new diene-forming side reaction during tungsten-catalyzed alkynol cycloisomerization has been discovered.

Glycal scavenging in the synthesis of disaccharides using mannosyl iodide donors

Abstract: High mannose glycans composed of α (1→2) and α (1→6) branched sugars are important components of the HIV-associated envelope glycoprotein, gp120. These substructures can be efficiently prepared in solution from glycosyl iodide precursors requiring only a slight excess of the iodide donor, which offers advantages over solid-phase methods that require more than 5 equiv of donor. During the reaction, excess iodide is converted to a glycal that is not easily separated from the desired disaccharide. To overcome this difficulty, a phase-trafficking methodology that relies upon nucleophilic interception of the 1,2 anhydrosugar resulting from oxidation of the glycal has been developed.

Effective One-pot Synthesis of H type 1 and 2 Trisaccharide Derivatives Using Glycal Epoxide

Abstract: We describe an efficient synthesis of H type 1 and 2 trisaccharides by one-pot glycosylation involving glycosidation of glycal epoxide.

Unusual Dimethyl Ketal from Cycloadduct of 4,6-O-Benzylidene-D-allal and Dichloroketene

Abstract: Glycal derivatives are useful building blocks in organic synthesis as well as in carbohydrate chemistry. Cycloadditions of dichloroketene to tri-O-benzyl or tri-O-acetylD-glucal and D-galactal were reported to produce α-oriented cyclobutanone ring, and the resulting bicyclic cyclobutanones were converted into lactone compounds by oxidation. Although they showed high stereo and regioselectivity with moderate yield, this methodology has not been widely applied for synthetic purpose. For the last few years, we have studied the cycloaddition of ketene to glucal, galactal, and allal derivatives and their application for the synthesis of C-glycoside derivatives and modified nucleosides. Even though, in case of allal, β-oriented cyclobutane ring formation is reported, no direct evidence supporting the face selectivity of dichloroketene cycloaddition to allal derivatives has been reported yet. Thus herein we report the X-ray structure of an unusual ketal from allal-derivative as the evidence that the facial selectivity of cycloaddition to glycal is controlled by the stereochemistry of C-3 constituent and discuss the mechanism for the formation of the unsual dimethyl ketal. To substantiate the evidence for facial selectivity, glucal and allal derivatives (1 and 3, respectively) were subject to dichloroketene cycloaddition reaction and treated with sodium methoxide in methanol. As expected, 3-O-benzyl4,6-O-benzilidene-D-glucal (1) was converted to C-1 and C-2 dialkylated C-glycoside, 3-O-benzyl-4,6-O-benzylidene1-dichloromethyl-2-methoxycarbonyl-1,2-dideoxy-α-D-glucopyranoside (2) in 73% yield. To our surprise, 3-O-benzyl4,6-O-benzylidene-D-allal (3) provided two products, O-benzyl-4,6-O-benzylidene-1-dichloromethyl-2-methoxycarbonyl-1,2-dideoxy-β-D-altropyranoside (4a) and dimethyl ketal (5a), in 36% and 29% isolated yield from allal (3), respectively (Scheme 1). The stereochemistry of C2 of 2 was determined by coupling constant between H2 and H3 (9.3 Hz, 1,2-diaxial orientation) and the previous results from glucal and galactal. Although C-glycoside from allalderivative has not been reported in the literature, methoxy carbonyl group on C2 of 4a was determined to orient axially based on coupling constant between H2 and H3 (3 Hz, 1,2diequatorial). This assignment of stereochemistry of C2 was confirmed by X-ray structure of 5a. In solid state the ketal (5a) has chair conformation of benzlylidene unit, twisted chair conformation of six membered sugar ring, and axial orientation of C3 benzyloxy substituent. Besides, more importantly, cyclobutanone is located on β-face of sugar ring, showed in Figure 1. This stereochemistry is attributed to the steric hindrance of bulky group on C3, which prevented dichloroketene from reacting on the α-face of allal effectively. To the best of our knowledge, the x-ray structure of allal-derived cycloaddition products has not been disclosed yet. Accordingly, we can

Transformation of Glycals into 2,3‐Unsaturated Glycosyl Derivatives

Abstract: Various elimination procedures conducted on appropriate pyranoid and furanoid carbohydrate derivatives, especially on O-protected glycosyl halides afford cyclic vinyl ethers which Fischer (inappropriately) named glycals. These are used extensively in general organic synthesis and for the preparation of non-carbohydrate natural products as well as biologically important complex carbohydrates and glycoconjugates. The best known member, tri-O-acetyl-D-glucal, is normally made from tetra-O-acetyl-alpha-D-glucopyranosyl bromide, is commercially available, and is used very frequently in this chapter to represent the family in examples of the reactions under discussion. Because of the pronounced region- and stereoselectivities with which their addition reactions can be conducted, glycal derivatives are of major importance in synthesis. They also, however, take part in rearrangement processes that, likewise, have proved useful for synthesis. The principal one involves nucleophilic substitution of the allylic group with allylic rearrangement and results in products having double bonds in the 2, 3 positions and new substituents at the anomeric centers. By far the simplest and most commonly used way to this conversion involves the removal of the allylic substituent of the glycal and the generation of highly resonance-stabilized oxocarbenium ion intermediate. This may then react with nucleophiles at the anomeric center to give products as mixtures of diastereomers. Many examples and variations of this theme are described and form the major part of this chapter, but other ways are also considered Almost no formal mechanistic studies have been carried out on the reactions in this chapter. Categorization of mechanism required for the treatment of this topic has been done on the basis of conditions used, product identification and largely, chemical intuition. Keywords: glycals; transformation; oxocarbenium ions; regioselectivity; diasterioselectivity; nucleophilic substitutions; homoallylic center; addition-elimination reactions; palladium; leaving groups; electrocyclic reactions; unsaturated compounds; free sugars; glycosyl peroxides; glycosyl caroxylates; S-glycosides; glycosyl halides; glycosyl azides; glycosyl phosphonates; glycosyl hydrides; furanoid glycols; intramolecular applications; reverse reaction; reaction variations; scope; limitations; configuration; experimental procedures; other methods

Methods for preparing enzymatic substrate analogs useful as inhibitors of bacterial heptosyl-transferases and biological applications of the inhibitors

Abstract: The invention relates to a method for making osyl and hexoses derivatives of formula (1), especially 2-fluoro-2-deoxy derivatives, wherein R is a nucleoside such as adenosine, cytidine, guanosine, uridine and deoxy analogs such as 2-deoxy, X represents OH, halogen, particularly F, NH2, Y represents H, CH2OH, CH2NH2, CH2OPO3, CH2OSO3, Z represents O or S, and W represents O,NH, or CH2, said method comprising the steps of: a) stereoselective fluorophosphorylation of tetrapivaleate 8 to give β-gluco-type fluorophosphate, b) hydrogenation and deprotection to give a monophosphate, c) coupling said glycal with (R)P-morpholidate to give crude sugar nucleotide 1, or . alternatively, d)deacetylation then silylation of heptoglycal 7 to give tetrasilylated glycal, e)fluorophosphorylation of said glycal to give β-gluco type fluorophosphate, f) deprotection of the fluorophosphate and coupling radical R to give 1. Use of said derivatives as inhibitors of highly virulent proteins of pathogenic bacteria.

Towards a synthesis of vigabatrin using glycal chemistry.

Abstract: Application of the Ferrier rearrangement led to a novel carbohydrate based synthetic route to 4-aminohexenoic acid viz. (R) and (S)-vigabatrin. The potential of D- glucose or D-galactose as the chiral starting materials for the synthesis of (R) and (S)- vigabatrin has been explored.

Synthesis of a New Furanoid Glycal Auxiliary

Abstract: A route is investigated for the synthesis of 3-O-allyl-1,4-anhydro-5-O-tert-butyldiphenylsilyl-2-deoxy-D-erythro-pent-1-enitol. The highest overall yield was obtained when 5′-O-(tert-butyldiphenylsilyl)thymidine was converted to the corresponding furanoid glycal and subsequently 3-O-allylated.

The “Reverse Polarity” Approach to Ravidomycin. Aryl C‐Aminoglycosides from a Lithiated Aminoglycal.

Abstract: A three‐step sequence affects the regio‐ and stereospecific elaboration of an aryl C‐aminoglycoside from a simple aminoglycal and a quinone. Direct lithiation of the glycal followed by addition of the quinone, reduction of the quinol adduct, and hydroboration gives a product with a trans‐trans stereochemical relationship between the substituents at C1′, C2′, and C3′, appropriate for compounds in the ravidomycin series.

Glycosylation with Sulfoxides and Sulfinates as Donors or Promoters

Abstract: The efficient, stereocontrolled formation of glycosidic bonds is arguably the most fundamental reaction in glycoscience. This chapter surveys four recent distinct glycosylation methods united by the common theme of employing sulfoxides, or closely related sulfinates, either in the glycosyl donor itself or as an integral part of the promoter. In the first method (the sulfoxide method), a glycosyl sulfoxide, the donor, is coupled to an acceptor alcohol by means of an activating agent to give the glycosidic bond. The activating agent is typically triflic anhydride, but other compounds have been used. In the second method (the thiogylcoside method) the donor is thioglycoside. It is activated by means of a promoter derived from the reaction of trifluoromethanesulfonic anhydride and thiosulfinate, a sulfinaminde, or diphenylsulfoxide before coupling to an acceptor alcohol. The third method is dehydrative coupling. This chapter is concerned only with the recent variations in which dehydration is achieved by means of a combination of diaryl sulfoxides and trifluoromethanesulfonic acid. The last method (the oxidative method), involves the direct oxidative glycosylation of glycals. This method differs significantly from the other methods since it does not employ a traditional anomeric derivative as glycosly donor, but derives one from the formal oxidation of glycal. At some time in the activation process, all four methods typically involve the reaction of a sulfoxide, or sulfinate with trifluoromethanesulfonic anhydride. All four methods possess the distinct advantage of using readily prepared, stable gylcosyl donors. Three of them are metal-free and two of them are capable of coupling to enable the most hindered unreactive alcohols in a matter of minutes at low temperature. These methods are some of the most powerful available for the formation of glycosidic linkages. Keywords: glycoslyation; mechanisms; oxidative method; sulfoxide method; dehydrative method; thioglycoside/sulfinate method; scope; limitations; donors; acceptors; N-Glycosides; nucleosides; C-Glycosides; sulfoxides; promoters; bond formation; synthesis applications; method comparisons; solvents; functional group compatibility; pyranoside; furnanosides; experimental procedures

Unusual Dimethyl Ketal from Cycloadduct of 4,6‐O‐Benzylidene‐D‐allal and Dichloroketene.

Abstract: Glycal derivatives are useful building blocks in organic synthesis as well as in carbohydrate chemistry. Cycloadditions of dichloroketene to tri-O-benzyl or tri-O-acetylD-glucal and D-galactal were reported to produce α-oriented cyclobutanone ring, and the resulting bicyclic cyclobutanones were converted into lactone compounds by oxidation. Although they showed high stereo and regioselectivity with moderate yield, this methodology has not been widely applied for synthetic purpose. For the last few years, we have studied the cycloaddition of ketene to glucal, galactal, and allal derivatives and their application for the synthesis of C-glycoside derivatives and modified nucleosides. Even though, in case of allal, β-oriented cyclobutane ring formation is reported, no direct evidence supporting the face selectivity of dichloroketene cycloaddition to allal derivatives has been reported yet. Thus herein we report the X-ray structure of an unusual ketal from allal-derivative as the evidence that the facial selectivity of cycloaddition to glycal is controlled by the stereochemistry of C-3 constituent and discuss the mechanism for the formation of the unsual dimethyl ketal. To substantiate the evidence for facial selectivity, glucal and allal derivatives (1 and 3, respectively) were subject to dichloroketene cycloaddition reaction and treated with sodium methoxide in methanol. As expected, 3-O-benzyl4,6-O-benzilidene-D-glucal (1) was converted to C-1 and C-2 dialkylated C-glycoside, 3-O-benzyl-4,6-O-benzylidene1-dichloromethyl-2-methoxycarbonyl-1,2-dideoxy-α-D-glucopyranoside (2) in 73% yield. To our surprise, 3-O-benzyl4,6-O-benzylidene-D-allal (3) provided two products, O-benzyl-4,6-O-benzylidene-1-dichloromethyl-2-methoxycarbonyl-1,2-dideoxy-β-D-altropyranoside (4a) and dimethyl ketal (5a), in 36% and 29% isolated yield from allal (3), respectively (Scheme 1). The stereochemistry of C2 of 2 was determined by coupling constant between H2 and H3 (9.3 Hz, 1,2-diaxial orientation) and the previous results from glucal and galactal. Although C-glycoside from allalderivative has not been reported in the literature, methoxy carbonyl group on C2 of 4a was determined to orient axially based on coupling constant between H2 and H3 (3 Hz, 1,2diequatorial). This assignment of stereochemistry of C2 was confirmed by X-ray structure of 5a. In solid state the ketal (5a) has chair conformation of benzlylidene unit, twisted chair conformation of six membered sugar ring, and axial orientation of C3 benzyloxy substituent. Besides, more importantly, cyclobutanone is located on β-face of sugar ring, showed in Figure 1. This stereochemistry is attributed to the steric hindrance of bulky group on C3, which prevented dichloroketene from reacting on the α-face of allal effectively. To the best of our knowledge, the x-ray structure of allal-derived cycloaddition products has not been disclosed yet. Accordingly, we can

Models for the Synthesis of Pluramycin Antibiotics. Rearrangement of Mono-Protected Aminoglycal-Substituted Cyclohexadienediols.

Abstract: A two‐step sequence converts protected glycal‐substituted quinols to aryl bis C‐glycals in which one or both of the substituents is an aminoglycal. First, a lithiated glycal undergoes 1,2‐addition to the carbonyl group of a protected glycal‐bearing quinol, leading to a mono‐protected cyclohexadienediol. Then a BF3‐etherate‐catalyzed “dienol phenol‐type” rearrangement converts the adduct to an aryl bis C‐glycal. The glycal moiety that was originally a substituent on the quinol substrate is the substituent that migrates. The presence of the amino group does not introduce complications. This sequence provides models for the rapid access to intermediates for pluramycin synthesis.