The Composition of Keto Aldoses in Aqueous Solution as Determined by NMR Spectroscopy

Keto aldoses usually form complex mixtures of equilibrating isomers in solution. This is due to the two different positions that may be used for ring closure in dicarbonyl sugars. The composition of various 2‐keto aldoses 1 – 5 and 8 , the 3‐keto aldose 2‐deoxy‐D ‐erythro‐hexos‐3‐ulose ( 9 ), and the ketose 1‐deoxy‐D ‐ribulose ( 10 ) in aqueous solution has been determined by NMR spectroscopy. The investigated keto aldoses form equilibria containing three to fifteen isomers. Among various furanose and pyranose ring structures stemming from 1,4‐, 1,5‐, 2,5‐, and 2,6‐cyclization, bicyclic forms were also found in several cases. The 2‐keto aldoses mainly exist as hydrated isomers in H₂O. Therefore, these forms and their proportions were compared to forms found in two homomorphous aldoses and one homomorphous ketose as model compounds. Besides the NMR data, also the composition of the 2‐keto aldoses agreed with the average of forms found in the model compounds, a finding that might eventually be useful for deducing the composition of other keto aldoses.     

3‐Deoxy‐β‐d‐ribo‐hexopyranose (3‐deoxy‐β‐d‐glucopyranose)

The β‐pyranose form, (III), of 3‐deoxy‐d ‐ribo‐hexose (3‐deoxy‐d ‐glucose), C₆H₁₂O₅, crystallizes from water at 298 K in a slightly distorted ⁴C₁ chair conformation. Structural analyses of (III), β‐d ‐glucopyranose, (IV), and 2‐deoxy‐β‐d ‐arabino‐hexopyranose (2‐deoxy‐β‐d ‐glucopyranose), (V), show significantly different C—O bond torsions involving the anomeric carbon, with the H—C—O—H torsion angle approaching an eclipsed conformation in (III) (−10.9°) compared with 32.8 and 32.5° in (IV) and (V), respectively. Ring carbon deoxygenation significantly affects the endo‐ and exocyclic C—C and C—O bond lengths throughout the pyranose ring, with longer bonds generally observed in the monodeoxygenated species (III) and (V) compared with (IV). These structural changes are attributed to differences in exocyclic C—O bond conformations and/or hydrogen‐bonding patterns superimposed on the direct (intrinsic) effect of monodeoxygenation. The exocyclic hydroxymethyl conformation in (III) (gt) differs from that observed in (IV) and (V) (gg).     

New approach to l'C‐modified riboside scaffold via stereoselective functionalization of D‐(+)‐ribonic‐y‐lactone

We describe the preparation and spectroscopic properties of a novel class of nucleoside analogues in which a phenyl sulfonyl methylene group is attached to the 1′‐carbon atom of P‐D‐ribofuranose. The glyco‐sylation of 5‐O‐(tert‐butyldiphenylsilyl)‐2,3‐O‐isopropylidene‐D‐ribofuranolactone lb with phenyl methyl‐lithium sulfone in THF at ?60° C afforded 5‐O‐(tert‐butyldiphenylsilyl)‐1′‐(benzenesulfonylmethylene)‐2′,3′‐O‐isopropylidene‐α‐D‐ribofuranose 2b . When subjected to deoxydative reaction conditions with boron trifluoride etherate in the presence of triethylsilane at ?45° C, lactol 2b was converted into 2′,3′‐O‐isopro‐pylidene‐1′‐deoxy‐1′‐(benzenesulfonylmethylene)‐β‐D‐ribofuranose 4b with excellent stereocontrol over the anomeric carbon in moderate yield. This method has the potential for the development of a wider array of useful probes derived from 1′‐deoxy‐β‐D‐ribofuranose for nucleic acid research and for antisense therapeutic agents through further functionalization of the coupled sulfonyl group.     

Chain elongation of aldoses by indium-mediated coupling with 3-bromopropenyl esters

[Chemical reaction: see text] A procedure is described for acyloxyallylation of unprotected aldoses with two functionalized reagents: 3-bromopropenyl acetate and 3-bromopropenyl benzoate. The reaction is performed in ethanol or a dioxane/water mixture in the presence of indium metal. The products are deesterified in the workup to afford unsaturated polyols, which are isolated as mixtures of two diastereomers. The major diastereomers are subjected to ozonolysis to afford new aldoses, which have been elongated by two carbon atoms compared to the starting materials. The new aldoses all have lyxo configuration at positions 2, 3, and 4.     

6‐Deoxyhexoses from l‐Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

In the search for alternative non‐metabolizable inducers in the l ‐rhamnose promoter system, the synthesis of fifteen 6‐deoxyhexoses from l ‐rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3‐acetonide of rhamnonolactone allows inversion of configuration at C4 and/or C5 of rhamnose to give 6‐deoxy‐d ‐allose, 6‐deoxy‐d ‐gulose and 6‐deoxy‐l ‐talose. Highly crystalline 3,5‐benzylidene rhamnonolactone gives easy access to l ‐quinovose (6‐deoxy‐l ‐glucose), l ‐olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic fluorination of rhamnal gives a mixture of 2‐deoxy‐2‐fluoro‐l ‐rhamnose and 2‐deoxy‐2‐fluoro‐l ‐quinovose. Biotechnology provides access to 6‐deoxy‐l ‐altrose and 1‐deoxy‐l ‐fructose.     

Fluorescence Dynamics of Monocyclodextrin– and Bis(thiol‐cyclodextrin)–Coumarin C153 Complexes

The solvation and confinement of coumarin C153 within supramolecular host/guest complexes based on β‐cyclodextrin (β‐CD) and 6‐deoxy‐6‐thio‐β‐cyclodextrin (β‐CD‐SH) in water are studied by fluorescence spectroscopy. For β‐CD/C153, the 1:1 complex is proposed, and for β‐CD‐SH/C153 both the 1:1 and 2:1 complexes are believed to be formed. The 2:1 β‐CD‐SH/C153 complex has an association constant of 4.2×10⁵ M ^?1 and a C153 population of 82 %, which are interestingly high values, indicating that the proposed β‐CD‐SH dimers structure are connected by covalent disulfide bonds; this is supported by mass spectrometry. Solvation related to fast hydrogen‐bond rearrangement as a part of fluorescence relaxation is determined by the ultrafast components of time‐resolved spectroscopy to be 3 and 7 ps for the 1:1 β‐CD/C153 and 2:1 β‐CD‐SH/C153 complexes, respectively.     

Probing the Interaction of the Hydroxy Group at C(4) of Lactone‐Type Inhibitors with β‐Glucosidases and β‐Galactosidases

The inhibition of the β‐glucosidases from sweet almonds and from Caldocellum saccharolyticum by the 4‐amino‐4‐deoxy lactam 11 , the 4‐deoxy lactam 12 , and the corresponding imidazoles 13 and 14 was compared to the inhibition by the hydroxy analogues 1 and 3 . Substitution of the OH group at C(4) by an amino group or by hydrogen weakened the inhibition by ΔΔG_diss = + 1.9 to + 3.1 kcal/mol. Similarly, the inhibition of the β‐galactosidase from bovine liver and from E. coli by the 4‐deoxy lactam 12 and the imidazole 14 , as compared to the one by the galacto‐configured lactam 9 and imidazole 10 , is weakened by deoxygenation at C(4) (ΔΔG_diss = + 2.6 and 4.5 kcal/mol, resp.). The effect of these substitutions on the inhibition of the C. saccharolyticum β‐glucosidase is slightly stronger than the one on the sweet almonds β‐glucosidases. The effect is also stronger on the inhibition by the imidazoles than by the lactams, and depends on the flexibility of the inhibitors. The amino and deoxy lactams 11 and 12 were prepared from the galactonolactam‐derived triflate 17 by substitution with azide and hydride, respectively, followed by hydrogenation. Azidation of the galacto‐configured imidazopyridine‐derived triflate 24 and hydrogenation gave the amino‐imidazole 13 . The deoxy lactam 20 was transformed to the manno‐ and gluco‐configured deoxy‐imidazoles 29 and 30 via the thionolactam 28 . Hydrogenolytic deprotection of 30 gave the deoxy‐imidazole 14 .     

Phormidolides B and C,Cytotoxic Agents from the Sea: Enantioselective Synthesis of the Macrocyclic Core

New cytotoxic polyketide macrolides named phormidolides B and C were isolated from a marine sponge of the Petrosiidae family collected off the coast of Pemba (Tanzania). The isolation, structure elucidation, and enantioselective synthesis of three diastereomers of the macrocyclic core is described herein. The described synthetic methodology started from 2‐deoxy‐D ‐ribose or 2‐deoxy‐L ‐ribose and afforded the desired macrocycles with high enantiomeric purity. The key step of the synthesis is the formation of the Z‐trisubstituted double bond using a Julia–Kocienski olefination. The versatility of the synthetic methodology may provide access to other enantiopure macrocycles by making changes in the starting materials or chiral inductors.     

介孔结构Fe/N/C作为质子交换膜燃料电池氧还原催化剂

燃料电池具有高效、低排放等优势,非常有希望作为未来电动汽车的能源转化装置.目前,燃料电池的商业化受制于昂贵的铂基催化剂,特别是动力学迟缓的阴极氧还原反应(ORR)铂催化剂. Fe/N/C被认为是最有潜力的ORR非贵金属催化剂,但其活性仍远低于Pt催化剂,必须依靠增加载量来弥补其与Pt催化剂的活性差距.然而,较厚的催化层(~100mm)会降低阴极传质速率.因此,改善Fe/N/C阴极的传质是提高电池性能的重要途径.
　　本文选择高N含量的2-氨基苯并咪唑(ABI)为氮源,通过水热聚合包覆在碳黑表面,然后掺入FeCl3,经高温热解/酸洗制备了Fe/N/C-ABI催化剂,并与基于间苯二胺的微孔型Fe/N/C催化剂(Fe/N/C-PmPDA)进行比较. Ar等温吸附-脱附结果表明, Fe/N/C-ABI催化剂具有较高的比表面积(662 m2/g)和丰富的双级孔结构(微孔和介孔);透射电镜表征显示Fe/N/C-ABI催化剂具有中空结构,介孔孔径大约为10–25 nm.而Fe/N/C-PmPDA催化剂具有相当的比表面积(656 m2/g),但以微孔为主,基本不含介孔.旋转环圆盘电极(RRDE)测试表明,在0.1 mol/L H2SO4溶液中, Fe/N/C-ABI催化剂的起始还原电位为0.92 V,在0.8 V电位下质量电流密度可达9.21 A/g;而Fe/N/C-PmPDA催化剂具有相近的起始电位,但具有更高的催化活性,质量电流密度为13.4 A/g.氢氧燃料电池(PEMFC)系统测试结果表明, Fe/N/C-ABI催化剂在1个背压和80oC测试条件下的最大功率密度达710 mW/cm2,高于Fe/N/C-PmPDA催化剂(616 mW/cm2).燃料电池与RRDE测试活性顺序的差异归结于Fe/N/C-ABI的中空球状结构. PEMFC工作时阴极会产生大量的水,很容易堵塞氧气传输通道. Fe/N/C-ABI的介孔结构可以作为水的产生和排除的缓存空间,也有利于提高O2传质,从而提高燃料电池性能.本文为具有高传质速率的Fe/N/C催化剂研制提供了一种新思路.     

Field desorption mass spectral fragmentation of monosaccharide isomers

Field desorption ionization of selected monosaccharide isomers by potassium ion attachment in high fields is described. The ionization is obtained with a tungsten wire activated with carbon needles and covered with KH₂PO₄ salt. In addition to the potassium cationized molecular ions, reproducible fragmentation was obtained at 10 mA and 20 mA typical of the various monosaccharides. For instance, D-glucose tends to lose a water molecule, whereas D-fructose loses primarily methanol under similar conditions. Methanol elimination is suggested to be characteristic of furanoidal ketoses and water elimination for pyranoidal aldoses, whereas glycol elimination occurs for furanoidal aldoses.     

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.     

Preparation of a permethylated β‐cyclodextrin chiral stationary phase by one‐pot hydrosilylation and immobilization at the C2 position for chiral high‐performance liquid chromatography

A novel cyclodextrin intermediate, mono‐2^A‐allylcarbamido‐2^A‐deoxy‐permethylated β‐cyclodextrin, was synthesized by reacting allylamine and newly prepared mono‐2^A‐azido‐2^A‐deoxy‐permethylated β‐cyclodextrin by the Staudinger reaction and anchored onto porous silica beads by a one‐pot hydrosilylation and immobilization procedure to afford a novel chiral stationary phase. This stationary phase acts as a new member of the previous chiral stationary phase series immobilized on the cyclodextrin C2 position. This stationary phase depicted enantiomeric separation abilities toward a series of bicyclic and tricyclic racemates under reversed‐phase conditions. The resolutions for hesperetin and naringenin achieved on the current phase reached 3.91 and 1.11, respectively, much higher than the previous permethylated β‐cyclodextrin with the linkage at the C6 position.     

Novel Regioselectively 6‐Functionalized Cationic Cellulose Polyelectrolytes Prepared via Cellulose Sulfonates

The synthesis of new 6‐deoxy‐6‐trialkylammonium cellulose derivatives obtained by nucleophilic displacement reactions of p‐toluenesulfonyl celluloses with various amines is described. Water soluble cellulosics could be prepared using a N,N‐dimethylformamide/water mixture as the reaction medium. Detailed studies concerning the influence of reaction time and temperature as well as the water content on the solubility of the products were carried out. Even the synthesis of large sample amounts was possible using optimized reaction conditions. The 6‐deoxy‐6‐trialkylammonium cellulose derivatives are water‐soluble even at low degrees of substitution, i. e., in the range of 0.2 and 0.5. The structure was confirmed by means of ¹H and ¹³C NMR spectroscopies.     

Highly Efficient Stereospecific Preparation of Tn and TF Building Blocks Using Thioglycosyl Donors and the Ph2SO/Tf2O Promotor System*

The activation of 2‐azido‐2‐deoxy Tn and TF thioglycosyl donors by the powerful thiophilic promoter system Ph₂SO/Tf₂O has been investigated. Glycosylation of an Fmoc‐protected threonine derivative gave 1,2‐cis glycosides in high yields and excellent stereoselectivities. The galactosylation of phenyl 2‐azido‐4,6‐O‐benzylidene‐2‐deoxy‐1‐thio‐β‐D‐galactopyranoside was achieved in high yield and without orthoester formation using a trichloroacetimidate donor carrying a 2‐O‐(2,5‐difluorobenzoyl) group. The anomeric thiophenyl group of the constructed TF disaccharide could directly be activated by the van Boom promotor for the glycosylation of a threonine derivative.     

Oligonucleotide Analogues with a Nucleobase‐Including Backbone:, Part 6, 2‐Deoxy‐D‐erythrose‐Derived Phosphoramidites: Synthesis and Incorporation into 14‐Mer DNA Strands

Two modified DNA 14‐mers have been prepared, containing either a 2‐deoxy‐D ‐erythrose‐derived adenosine analogue carrying a C(8)−CH₂O group (deA*), or a 2‐deoxy‐D ‐erythrose‐derived uridine analogue, possessing a C(6)−CH₂O group (deU*). These nucleosides are linked via a phosphinato group between O−C(3′) (deA* and deU*) and O−C(5′) of one neighbouring nucleotide, and between C(8)−CH₂O (deA*), or C(6)−CH₂O (deU*) and O−C(3′) of the second neighbour. N⁶‐Benzoyl‐9‐(β‐D ‐erythrofuranosyl)adenine ( 3 ) and 1‐(β‐D ‐erythrofuranosyl)uracil ( 4 ) were prepared from D ‐glucose, deoxygenated at C(2′), and converted into the required phosphoramidites 1 and 2 . The modified tetradecamers 31 and 32 were prepared by solid‐phase synthesis. Pairing studies show a decrease in the melting temperature of 7 to 8 degrees for the duplexes 31 ⋅ 30 and 32 ⋅ 29 , as compared to the unmodified DNA duplex 29 ⋅ 30 . A comparison with the pairing properties of tetradecamers similarly incorporating deoxyribose‐ instead of the deoxyerythrose‐derived nucleotides evidences that the CH₂OH substituent at C(4′) has no significant effect on the pairing.     

保护的几丁寡糖及结构类似物的合成：复杂氨基寡糖合成的通用方法

建立了逐步合成具有重要生物活性的2-脱氧-2-氨基葡萄糖寡糖链的通用方法。采用邻苯二甲酰基保护氨基、硫代苯基为还原末端的离去基团,以氨基葡萄糖为起始原料,几种保护的几丁寡糖及结构类似物被合成：3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→4）-（3-O-乙酰基-6-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基）-b-D-吡喃葡萄糖甲苷（4）、3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→4）-（3-O-乙酰基-6-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖）-（1→4）-（3-O-乙酰基-6-O-苄基-2-脱氧-2-邻苯二甲酰亚氨基）-b-D-吡喃葡萄糖甲苷（6）、3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→3）-（4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基）-b-D-吡喃葡萄糖甲苷（8）、3-O-乙酰基-4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖-（1→3）-（4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基-b-D-吡喃葡萄糖）- （1→3）-（4,6-O-亚苄基-2-脱氧-2-邻苯二甲酰亚氨基）- b-D-吡喃葡萄糖甲苷（10）。所合成化合物通过核磁共振和质谱分析确证了其化学结构。     

Synthesis and Amphiphilic Behavior of N,N‐Bis‐glucosyl‐1,5‐benzodiazepin‐2,4‐dione

Abstract

Glucosyl‐1,5‐benzodiazepin‐2,4‐diones were synthesized in order to study the influence of the glucidic moiety on the amphiphilic behaviour. The glucosyl groups include 6‐deoxy‐D‐glucopyranos‐6‐yl and 6‐deoxy‐3‐O‐R‐D‐glucopyranos‐6‐yl (R = n ? C _n H _2n+1; n = 1, 8, 10 and 12). Variation in the length of the hydrocarbon chain allowed comparison of such amphiphilic data as water solubility (Sw) and surface tension (γ) values. At 25°C, the glucopyranosyl benzodiazepines with R = H and CH₃ show a higher water solubility than the starting 1,5‐benzodiazepin‐2,4‐diones. Some other glucidic benzodiazepine derivatives with an appropriate alkyl chain at C‐3 carbon of the D‐glucopyranose present a variable hydrosolubility and surface tension γ values close to 43 to 46 mN · m^?1 at the corresponding saturation. Moreover, according to preliminary tests, these compounds seem to show a better affinity for the blood brain barrier.     

1H and 13C NMR and X‐ray diffraction data for a diosgenyl N,O‐protected glucopyranoside

The assignments of ¹H and ¹³C NMR chemical shifts together with x‐ray diffraction data for synthesized diosgenyl 3,4,6‐tri‐O‐acetyl‐2‐deoxy‐2‐tetrachlorophthalimido‐β‐D ‐glucopyranoside are described. The structure of this glycoside was established by using homo‐ and heteronuclear two‐dimensional NMR techniques. X‐ray diffraction data for this compound are also reported. Copyright © 2002 John Wiley & Sons, Ltd.     

Friccohenics of Continuum and Non‐Continuum Models for Liquid Flow Applied for Heteromolecular Interaction of DNA Bases and Sugars Estimated with Mansingh Equation

Newtonian and non‐Newtonian liquids widely characterize continuum and non‐continuum models for flows, thus, viscous (continuum) and drop wise (non‐continuum) flows of water and aqueous nucleotides (2‐deoxy adenosine‐DOA, thymidine‐TMD) and nucleosides (guanosine monophosphate‐GMP, adenosine triphosphate‐ATP) with integral unites‐2‐deoxy ribose‐DOR (referred as DNA bases and sugars) have been studied with Survismeter. Time data for viscous (t and drop wise (dt) flows along with drop counts (n) for aqueous solutions of 0.4–1.4 millimol (mm) DNA base and sugars with survismetere at 288.15, 293.15, and 298.15 K are measured for viscosities and surface tension, respectively. The t and n are fitted in Mansingh equation for Friccohesity (σ) calculation that determines dipole moment (µ). The t, dt, and n data are measured for water from 15 to 70°C at an interval of 5°C for standard equation for dipole moment calculation. The t, dt and n values decrease with temperature where the σ is directly proportional to μ values with slight increase with compositions and decreases with temperatures. A continuous decrease in μ values with compositions is noted with slightly higher decrease at 288.15 with both millimol and temperature. The higher decrease with temperatures weakens Coulombic forces ((q₁ · q₂)/r², with charges q₁ and q₂, and radii r)) where σ increase.     

Synthesis and Evaluation of Paromomycin Derivatives Modified at C(4′)

The 2‐amino‐2‐deoxy‐α‐D ‐glucopyranosyl moiety (ring I) of paromomycin was replaced by a 2,4‐diamino‐2,4‐dideoxy‐α‐D ‐glucopyranosyl, 2,4‐diamino‐2,4‐dideoxy‐α‐D ‐galactopyranosyl, 2‐amino‐2‐deoxy‐α‐D ‐galactopyranosyl, or 3,4,5‐trideoxy‐4‐aza‐α‐D ‐erythro‐heptoseptanosyl moiety to investigate the effect of the substituent at C(4′) on the interaction with ribosomal RNA. The triflate 6 was prepared from the key intermediate pentaazido 3′,6′‐dibenzyl ether 5 , and the hexosulose 10 was obtained by oxidation of 5 with Dess–Martin's periodinane. Stereoselective reduction of 10 with NaBH₄ gave the alcohol 11 that was transformed into the triflate 12 . The epimeric hexaazides 7 and 13 were obtained by treating the triflates 6 and 12 , respectively, with tetrabutylammonium azide. Periodate cleavage of glycol 2 yielded the dialdehyde 24 that was reductively aminated with aniline and benzylamine to give the 3,4,5‐trideoxy‐4‐aza‐α‐D ‐erythro‐heptoseptanosides 25 and 26 , respectively. Standard azide reduction and debenzylation yielded 9 (2,4‐diamino‐2,4‐dideoxy‐α‐D ‐galactopyranosyl ring I), 13 (2‐amino‐2‐deoxy‐α‐D ‐galactopyranosyl ring I), 17 (2,4‐diamino‐2,4‐dideoxy‐α‐D ‐glucopyranosyl ring I), and 27 and 28 (3,4,5‐trideoxy‐4‐aza‐α‐D ‐erythro‐heptoseptanosyl ring I). The derivatives 9 and 13 possessing a D ‐galacto‐configured ring I were less active than the corresponding D ‐gluco‐analogues 17 and paromomycin ( 1 ), respectively. The C(4′)‐aminodeoxy derivative 17 (D ‐gluco ring I) and the known 4′‐deoxyparomomycin ( 23 ), prepared by a new route, displayed slightly lower antibacterial activities than paromomycin ( 1 ). Cell‐wall permeability is not responsible for the unexpectedly low activity for 17 , as shown by cell‐free translation assays. The results evidence that the orientation of the substituent at C(4′) is more important than its nature for drug binding and activity.