Synthesis of benzyl O-(2,3,3'-tri-O-acetyl-β-D-apiofuranosyl)-(1→3)-2,4-di-O-benzoyl-α-D-xylopyranoside and its X-ray structure

The protected apiose-containing disaccharide, benzyl O-(2,3, 3'-tri-O-acetyl-β-D-apiofuranosyl)-( 1→3)-2, 4-di-O-benzoyl-α-D-xylopyranoside, was synthesized and its X-ray structure provided.     

Enzymatic Synthesis of Nucleoside‐5′‐O‐(1‐thiophosphates) and (SP)‐Adenosine‐5′‐O‐(1‐thiotriphosphate)

Treatment of adenosine with PSCl₃ in trimethyl phosphate gave, after ion‐exchange chromatography, adenosine‐5′‐O‐monophosphate (AMP; 28%) and adenosine‐5′‐O‐monothiophosphate (AMPS; 48%). AMPS was studied as a thiophosphate residue donor in an enzymatic transphosphorylation with nucleoside phosphotransferase (NPase) of the whole cells of Erwinia herbicola. As exemplified by a number of natural and sugar‐ and base‐modified nucleosides, it was demonstrated that NPase of the whole cells of Erwinia herbicola catalyzes the transfer of both thiophosphate and phosphate residues with a similar efficiency. An incubation of AMPS in a phosphorylating extract of Saccharomyces cerevisiae (K‐phosphate buffer (0.3 M , pH 7.0); 3% glucose; 15 mM MgCl₂; 28°, 8 h), followed by ion‐exchange column chromatography afforded AMP (8%), AMPS (recovered, 23%), ATP (11%), and (S_P)‐adenosine‐5′‐O‐(1‐thiotriphosphate) ((S_P)‐ATPαS); (total yield 37%; 48% based on the consumed AMPS). For comparison of physicochemical properties, adenosine was chemically transformed into ATPαS as a mixture of the (S_P) (53%) and (R_P) (44%) diastereoisomers.     

Synthesis and Properties of O‐β‐D‐ribofuranosyl‐(1″→2′)‐guanosine‐5″‐ O‐phosphate and Its Derivatives

The efficient synthesis of O‐β‐D ‐ribofuranosyl‐(1″→2′)‐guanosine‐5″‐O‐phosphate and O‐β‐D ‐ribofuranosyl‐(1″→2′)‐adenosine‐5″‐O‐phosphate, minor tRNA components, have been developed, and their conformational properties were examined by NMR spectroscopy.     

Synthesis,Crystal Structure and Hydrolysis of a Novel Anhydrogalactosucrose: 2′‐Methoxyl‐O‐1′,4′:3′,6′‐dianhydro‐β‐D‐fructofuranosyl 3,6‐anhydro‐4‐chloro‐4‐deoxy‐α‐D‐galactopyranoside

A novel anhydrogalactosucrose derivative 2′‐methoxyl‐O‐1′,4′:3′,6′‐dianhydro‐β‐D‐fructofuranosyl 3,6‐anhydro‐4‐chloro‐4‐deoxy‐α‐D‐galactopyranoside ( 4 ) was prepared from 3,6:1′,4′:3′,6′‐trianhydro‐4‐chloro‐4‐deoxy‐galactosucrose ( 3 ) via a facile method and characterized by ¹H NMR, ¹³C NMR and 2D NMR spectra. The single crystal X‐ray diffraction analysis shows that the title molecule forms a two thee‐dimensional network structure by two kinds of hydrogen bond interactions [O(2) H(2)···O(7), O(5) H(5)···O(8)]. Its stability was investigated by acid hydrolysis reaction treated with sulfuric acid, together with the formation of 1,6‐Di‐O‐methoxy‐4‐chloro‐4‐deoxy‐β‐D‐galactopyranose ( 5 ) and 2,2‐Di‐C‐methoxy‐1,4:3,6‐dianhydromannitol ( 6 ). According to the result, the relative stability of the ether bonds in the structure is in the order: C(1) O C(5)≈C(3′) O C(6′)≈C(1′) O C(4′)>C(3) O C(6)≈C(1) O C(2′)>C(2′) O C(5′).     

Nucleosides XIII. Facile Synthesis of 4‐Amino‐1‐(2‐deoxy‐β‐D‐ribofuranosyl)quinazolin‐2‐one as a 2′‐Deoxycytidine Analog for Oligonucleotide Synthesis

4‐Amino‐1‐(2‐deoxy‐β‐D‐ribofuranosyl)quinazolin‐2‐one (4) was prepared by Barton deoxygenation from 4‐amino‐1‐(β‐D‐ribofuranosyl)quinazolin‐2‐one (3) as a 2′‐deoxycytidine analog.     

Semisynthesis of 3′(2′)‐O‐(Aminoacyl)‐tRNA Derivatives as Ribosomal Substrate

An efficient synthesis of (3′‐terminally) 3′(2′)‐O‐aminoacylated pCpA derivatives is described, which could lead to the production of (aminoacyl)‐tRNAs following T4 RNA ligase mediated ligation. The tetrahydrofuranyl (thf) group was used as a permanent protective group for the 2′‐OH of the cytidine moiety which can be removed during the purification of the 3′(2′)‐O‐aminoacylated‐pCpA. This approach allowed for a general synthesis of (3′‐terminally) 3′(2′)‐O‐aminoacylated oligonucleotides. The fully protected pCpA 14 was synthesized by phosphoramidite chemistry and treated with NH₃ solution to remove the 2‐cyanoethyl and benzoyl groups (→ 15 ; Schemes 1 and 2). The 2′‐O‐thf‐protected‐pCpA 15 was coupled with α‐amino acid cyanomethyl esters, and the products 20a – c were deprotected and purified with AcOH buffer to afford 3′(2′)‐O‐aminoacylated pCpA 21a – c in high yields. The 3′(2′)‐O‐aminoacylated pCpA were efficiently ligated with tRNA(? CA) to yield (aminoacyl)‐tRNA which was an active substrate for the ribosome.     

2,2′‐Anhydro‐1‐(3′,5′‐di‐O‐acetyl‐β‐D‐arabinofuranosyl)uracil,a cyclouridine nucleoside with a C4′‐endo furanosyl conformation

2,2′‐Anhydro‐1‐(3′,5′‐di‐O‐acetyl‐β‐D‐arabinofuranosyl)uracil, C₁₃H₁₄N₂O₇, was obtained by refluxing 2′,3′‐O‐(methoxymethylene)uridine in acetic anhydride. The structure exhibits a nearly perfect C4′‐endo (⁴E) conformation. The best four‐atom plane of the five‐membered furanose ring is O—C—C—C, involving the C atoms of the fused five‐membered oxazolidine ring, and the torsion angle is only −0.4 (2)°. The oxazolidine ring is essentially coplanar with the six‐membered uracil ring [r.m.s. deviation = 0.012 (5) Å and dihedral angle = −3.2 (3)°]. The conformation at the exocyclic C—C bond is gauche–trans which is stabilized by various C—H...π and C—O...π interactions.     

{5′‐O‐[Bis(4‐methoxyphenyl)(phenyl)methyl]‐2′‐deoxy‐β‐D‐threopentofuranosyl}thymine ethyl acetate 0.25‐solvate

The title compound, C₃₁H₃₂N₂O₇·0.25C₄H₈O₂, is a key intermediate in the synthesis of [¹⁸F]fluorine‐labelled thymidine (¹⁸F‐FLT), which is the most widely used molecular imaging probe for positron emission tomography (PET). The crystallographic asymmetric unit contains two independent thymine molecules plus one partially occupied site for an ethyl acetate molecule. The two independent thymine molecules show similar geometrical features, except that the dimethoxytrityl groups adopt different orientations with respect to the remainder of the molecule. Each thymine base adopts an anti conformation with respect to the attached deoxyribose ring, and the deoxyribose rings show C3‐endo puckering. The conformation of the side chain at the C1 position of the deoxyribose ring is gauche+. Intermolecular N—H...O and O—H...O hydrogen bonds link the molecules into one‐dimensional chains.     

The regioisomeric 1H(2H)‐pyrazolo[3,4‐d]pyrimidine N1‐ and N2‐(2′‐deoxy‐β‐D‐ribofuranosides)

In the title regioisomeric nucleosides, alternatively called 1‐(2‐deoxy‐β‐d ‐erythro‐furan­osyl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₁₀H₁₂N₄O₃, (II), and 2‐(2‐deoxy‐β‐d ‐erythro‐furan­osyl)‐2H‐pyrazolo­[3,4‐d]pyrimidine, C₁₀H₁₂N₄O₃, (III), the conformations of the gly­cosyl­ic bonds are anti [?100.4 (2)° for (II) and 15.0 (2)° for (III)]. Both nucleosides adopt an S‐type sugar pucker, which is C2′‐endo‐C3′‐exo (²T₃) for (II) and 3′‐exo (between ₃E and ⁴T₃) for (III).     

Ein neuer Zugang zu 2′‐O‐(2‐Methoxyethyl)ribonucleosiden ausgehend von D‐Glucose

A New Access to 2′‐ O ‐(2‐Methoxyethyl)ribonucleosides Starting from D ‐Glucose A new synthesis of 2′‐O‐(2‐methoxyethyl)ribonucleosides, building blocks for second‐generation antisense oligonucleotides, starting from D ‐glucose is presented. The key‐step is the transformation of 3‐O‐methoxyethylallofuranose to 2‐O‐(2‐methoxyethyl)ribose by NaIO₄ oxidation. Together with the 4′‐phenylbenzoyl protecting group, which results in crystalline intermediates, this synthesis provides an easy and cheap access to 2′‐O‐(2‐methoxyethyl)‐substituted ribonucleosides.     

Methyl 4‐O‐β‐D‐mannopyranosyl β‐D‐xylopyranoside

Methyl β‐D‐mannopyranosyl‐(1→4)‐β‐D‐xylopyranoside, C₁₂H₂₂O₁₀, (I), crystallizes as colorless needles from water, with two crystallographically independent molecules, (IA) and (IB), comprising the asymmetric unit. The internal glycosidic linkage conformation in molecule (IA) is characterized by a ϕ′ torsion angle (O5′_Man—C1′_Man—O1′_Man—C4_Xyl; Man is mannose and Xyl is xylose) of −88.38 (17)° and a ψ′ torsion angle (C1′_Man—O1′_Man—C4_Xyl—C5_Xyl) of −149.22 (15)°, whereas the corresponding torsion angles in molecule (IB) are −89.82 (17) and −159.98 (14)°, respectively. Ring atom numbering conforms to the convention in which C1 denotes the anomeric C atom, and C5 and C6 denote the hydroxymethyl (–CH₂OH) C atom in the β‐Xylp and β‐Manp residues, respectively. By comparison, the internal glycosidic linkage in the major disorder component of the structurally related disaccharide, methyl β‐D‐galactopyranosyl‐(1→4)‐β‐D‐xylopyranoside), (II) [Zhang, Oliver & Serriani (2012). Acta Cryst. C 68 , o7–o11], is characterized by ϕ′ = −85.7 (6)° and ψ′ = −141.6 (8)°. Inter‐residue hydrogen bonding is observed between atoms O3_Xyl and O5′_Man in both (IA) and (IB) [O3_Xyl...O5′_Man internuclear distances = 2.7268 (16) and 2.6920 (17) Å, respectively], analogous to the inter‐residue hydrogen bond detected between atoms O3_Xyl and O5′_Gal in (II). Exocyclic hydroxymethyl group conformation in the β‐Manp residue of (IA) is gauche–gauche, whereas that in the β‐Manp residue of (IB) is gauche–trans.     

Three different fluoro‐ or chloro‐substituted 1′‐deoxy‐1′‐phenyl‐β‐D‐ribofuranoses

Crystal structures are reported for three fluoro‐ or chloro‐substituted 1′‐deoxy‐1′‐phenyl‐β‐D‐ribofuranoses, namely 1′‐deoxy‐1′‐(2,4,5‐trifluorophenyl)‐β‐D‐ribofuranose, C₁₁H₁₁F₃O₄, (I), 1′‐deoxy‐1′‐(2,4,6‐trifluorophenyl)‐β‐D‐ribofuranose, C₁₁H₁₁F₃O₄, (II), and 1′‐(4‐chlorophenyl)‐1′‐deoxy‐β‐D‐ribofuranose, C₁₁H₁₃ClO₄, (III). The five‐membered furanose ring of the three compounds has a conformation between a C2′‐endo,C3′‐exo twist and a C2′‐endo envelope. The ribofuranose groups of (I) and (III) are connected by intermolecular O—H...O hydrogen bonds to six symmetry‐related molecules to form double layers, while the ribofuranose group of (II) is connected by O—H...O hydrogen bonds to four symmetry‐related molecules to form single layers. The O...O contact distance of the O—H...O hydrogen bonds ranges from 2.7172 (15) to 2.8895 (19) Å. Neighbouring double layers of (I) are connected by a very weak intermolecular C—F...π contact. The layers of (II) are connected by one C—H...O and two C—H...F contacts, while the double layers of (III) are connected by a C—H...Cl contact. The conformations of the molecules are compared with those of seven related molecules. The orientation of the benzene ring is coplanar with the H—C1′ bond or bisecting the H—C1′—C2′ angle, or intermediate between these positions. The orientation of the benzene ring is independent of the substitution pattern of the ring and depends mainly on crystal‐packing effects.