Studies directed toward the development of amide-linked RNA mimics: synthesis of the monomeric building blocks

A general approach toward the synthesis of all four monomeric building blocks of the ribonucleoside amino acids 3'-amino-5'-carboxymethyl-3',5'-dideoxy nucleosides in their protected forms is described that will facilitate the development of amide-linked RNA mimics.     

A new strategy for solid-phase depsipeptide synthesis using recoverable building blocks

The technique of choice for synthesis of small-scale depsipeptides is on a solid support. However, if expensive monomers have to be incorporated, solid-phase synthesis can quickly turn out to be unattractive because of its low atom economy. Herein, we describe a new type of recoverable and reuseable alpha-hydroxy acid building block for solid-phase synthesis and its application in the synthesis of a number of small cyclic depsipeptides. [structure: see text]     

De novo synthesis of oligosaccharides using a palladium-catalyzed glycosylation reaction

The natural all d- and/or unnatural all l-1,4- and 1,6-oligosaccharides were synthesized from furan alcohols using a palladium-catalyzed glycosylation reaction. The 1,4- and 1,6-alpha-manno-disaccharides were achieved in seven total steps starting from chiral furan alcohols. Similarly, 1,4- and 1,6-alpha-manno-trisaccharides were also synthesized in nine total steps. Key to the overall efficiency of this process was the use of highly diastereoselective palladium-catalyzed glycosylations, reductions, and dihydroxylations.     

Toward the modular synthesis of glycosaminoglycans: synthesis of hyaluronic acid disaccharide building blocks using a periodic acid oxidation

The synthesis of two differentially protected GluNAc-β(1→4)-GluA and GluA-β(1→3)-GluNAc disaccharide modules for the solid-phase assembly of hyaluronic acid are described. A periodic acid/chromium trioxide oxidation was the key transformation to facilitate access to the glucuronic acid moiety from glucose and should find wide application in the oxidation of primary alcohols.     

Total synthesis of woodrosin I--part 1: preparation of the building blocks and evaluation of the glycosylation strategy

The preparation of three building blocks required for the total synthesis of woodrosin I (1) is outlined, a complex resin glycoside bearing a macrolide ring which spans four of the five sugars of its oligosaccharide backbone. Key steps involve the enantioselective, titanium-catalyzed addition of dipentylzinc to 5-hexenal, the glycosylation of the resulting alcohol 18 with the glucose-derived trichloroacetimidate 7, and further elaboration of the resulting product 19 into disaccharide 22 on treatment with the orthogonally protected glycosyl donor 15. The trichloroacetimidate method is also used for the formation of the second synthon represented by disaccharide 38. A model study shows that the assembly of the pentasaccharidic perimeter of 1 depends critically on the phasing of the glycosylation events between fragments 22, 38 and the rhamnosyl donor 27 due to the severe steric hindrance in the product. A particularly noteworthy finding is the fact that diol 22 can be regioselectively glycosylated at the 3'-OH group in high yield without protection of the neighboring 2'-OH function.     

De novo synthesis of uronic acid building blocks for assembly of heparin oligosaccharides

An efficient de novo synthesis of uronic acid building blocks is described. The synthetic strategy relies on the stereoselective elongation of thioacetal protected dialdehydes 12 a and 17. The dialdehydes are prepared from D-xylose, a cheap and commercially available source. A highly stereoselective MgBr(2)OEt(2)-mediated Mukaiyama aldol addition to C4-aldehyde 12 a is performed to obtain D-glucuronic acid building block 16, whereas L-iduronic acid building block 22 is prepared by MgBr(2)OEt(2)-mediated cyanation of C5-aldehyde 17. Synthesis of a heparin disaccharide demonstrates the utility of the de novo strategy for the assembly of glycosaminoglycan oligosaccharides.     

Synthesis of di-branched heptasaccharide by one-pot glycosylation using seven independent building blocks

[reaction: see text] We describe an efficient synthesis of di-branched heptasaccharide 1 having phytoalexin elicitor activity in soybeans by one-pot glycosylation. The synthesis involves chemo- and regioselective sequential six-step glycosylations using seven independent building blocks and sequential removal of acyl- and benzyl ether-type protecting groups. The coupling of seven building blocks requires only four chemoselective activitable leaving groups of glycosyl donors. Both the glycosylation and deprotection reactions can be achieved utilizing a parallel manual synthesizer.     

Asymmetric synthesis of alkaloids using polyfunctionalized chiral building blocks

Enantiopure N‐sulfinyl‐δ‐amino‐β‐ketoesters and isoquinolones, prepared from sulfinimines (N‐sulfinyl imines) are a new class of polyfunctionalized chiral building blocks. These building blocks provide easy access to enantiomerically pure, functionalized piperidines and tetrahydroisoquinolines with a minimum of chemical manipulation and protecting‐group chemistry. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:486–492, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10090     

Efficient synthesis of phosphotyrosine building blocks using imidazolium trifluoroacetate

We have successfully employed imidazolium trifluoroacetate as a replacement for tetrazole for efficient synthesis of phosphotyrosine. This modification is compatible with the protecting groups commonly used in solution phase and Fmoc-solid phase peptide synthesis.     

Isoprenoid homologation: A synthesis of isoprenoid alcohols using terpene building blocks

This paper describes the synthesis of linalool and nerolidol by means of a regioselective coupling of the hydroxy-sulfoxide 6a with prenyl-and geranylbromide, followed by reductive desulfurization.     

Improved synthesis of the enantiomers of propafenone using chiral building blocks

Summary A short and efficient synthesis of the enantiomers of the antiarrhythmic drug propafenone (1) is described using both (R)-isopropylideneglycerol tosylate and (S)-glycidyl tosylate as chiral building blocks. The key step of the high yield synthesis is the acetalization of the carbonyl group in 1-(2-hydroxyphenyl)-3-phenyl-1-propanone (2) which allows application of mild reaction conditions in the subsequent alkylation of the phenolic hydroxy group.With our best wishes dedicated to Prof. Dr.H. Achenbach on the occasion of his 65^th birthday     

Synthesis of modular building blocks using glycosyl phosphate donors for the construction of asymmetric N-glycans

Glycosyl phosphates are known as versatile donors for the synthesis of complex oligosaccharides both chemically and enzymatically. Herein, we report the stereoselective construction of modular building blocks for the synthesis of N-glycan using glycosyl phosphates as donors. We have synthesized four trisaccharide building blocks with orthogonal protecting groups, namely, Manβ2GlcNAc(OAc)₃β6GlcNAc (9), Manβ2GlcNAc-β6GlcNAc(OAc)₃ (15), Manβ2GlcNAc(OAc)₃β4GlcNAc (18) and Manβ2GlcNAcβ4GlcNAc(OAc) (22) for further selective elongation using glycosyltransferases. The glycosylation reaction using glycosyl phosphate was found to be high yielding with shorter reaction time. Initially, The phthalimide protected glucosamine donor was exploited to ensure the formation of β-glycosidic linkage and later converted to the N-acetyl group before the enzymatic synthesis. The selective deprotection of O-benzyl group was performed prior to enzymatic synthesis to avoid its negative interference.     

The first synthesis of tetraglucosyl glucitol having phytoalexin-elicitor activity in rice cells based on a sequential glycosylation strategy

We describe a highly convergent approach for the synthesis of the tetraglucosyl glucitol 1 and its derivatives 4, 5 and 6 which exhibit phytoalexin-elicitor activity in rice cells based on sequential glycosylation.     

Construction of N-glycan microarrays by using modular synthesis and on-chip nanoscale enzymatic glycosylation

An effective chemoenzymatic strategy is reported that has allowed the construction, for the first time, of a focused microarray of synthetic N-glycans. Based on modular approaches, a variety of N-glycan core structures have been chemically synthesized and covalently immobilized on a glass surface. The printed structures were then enzymatically diversified by the action of three different glycosyltransferases in nanodroplets placed on top of individual spots of the microarray by a printing robot. Conversion was followed by lectin binding specific for the terminal sugars. This enzymatic extension of surface-bound ligands in nanodroplets reduces the amount of precious glycosyltransferases needed by seven orders of magnitude relative to reactions carried out in the solution phase. Moreover, only those ligands that have been shown to be substrates to a specific glycosyltransferase can be individually chosen for elongation on the array. The methodology described here, combining focused modular synthesis and nanoscale on-chip enzymatic elongation, could open the way for the much needed rapid construction of large synthetic glycan arrays.     

A new linker for solid-phase synthesis of heparan sulfate precursors by sequential assembly of monosaccharide building blocks

A novel ester type linker which upon cleavage releases the glycans as carbamate protected aminoglycosides was successfully employed in the sequential assembly of L-idose and azido glucose monosaccharide building blocks to heparan sulfate precursors.     

A simplified strategy for the synthesis of dideoxyribonucleotide blocks

The rapid synthesis of dideoxyribonucleotide blocks in 60–85% isolated yields has been achieved by combining the phosphorylation and condensation steps in a sequential reaction series which also allows the recovery of unreacted nucleotides.     

Synthesis of lipophilic bisanthracene fluorophores: versatile building blocks toward the synthesis of new light-harvesting dendrimers

Lipophilic bisanthracene-based fluorophore and its derivatives were synthesized by the Suzuki-Miyaura cross-coupling reaction of 9-anthrylboronic acid with a substituted dibromobenzene. In addition to desirable fluorescent properties, these molecular systems were demonstrated to serve as versatile building blocks toward the synthesis of two types of new light-harvesting dendrimers due to their chemical stability.     

Linear synthesis of a protected H-type II pentasaccharide using glycosyl phosphate building blocks.

A linear synthesis of a fully protected H-type II blood group determinant pentasaccharide utilizing glycosyl phosphate and glycosyl trichloroacetimidate building blocks is reported. Envisioning an automated solid-phase synthesis of blood group determinants, the utility of glycosyl phosphates in the stepwise construction of complex oligosaccharides, such as the H-type II antigen, is demonstrated. Installation of the central glucosamine building block required the screening of a variety of nitrogen protecting groups to ensure good glucosamine donor reactivity and protecting group compatibility. The challenge to differentiate C2 of the terminal galactose in the presence of other hydroxyl and amine protecting groups prompted us to introduce the 2-(azidomethyl)benzoyl group as a novel mode of protection for carbohydrate synthesis. The compatibility of this group with traditionally employed protecting groups was examined, as well as its use as a C2 stereodirecting group in glycosylations. The application of the 2-(azidomethyl)benzoyl group along with a systematic evaluation of glycosyl donors allowed for the completion of the pentasaccharide and provides a synthetic strategy that is expected to be generally amenable to the solid support synthesis of blood group determinants.