Synthesis of a Chiral Hexane-1,6-Dinitrile from D-Glucose

Abstract

Using well-established methodology, D-glucose was transformed into a tribenzoyloxy cyclohexanone oxime derivative. Sodium azide treatment permitted the regiospecific exchange of the benzoyloxy group at a α-position relative to ketone oxime. Under standard Beckmann conditions the α-azido was oxime cleaved to provide an ω-dicyano compound.     

Synthesis of Novel Polyphosphate Analogues of Inositol 1,4,5-Trisphosphate

Abstract

The synthesis of novel polyphosphate mimics of inositol 1,4,5-trisphosphate, including ring-contracted and conformationally restricted analogues is reported.     

Stereoselective Synthiesis of Both Enantiomers of Disparlure from D-Glucose

D-Glucose was transformed stereoselectively into (7R,8S)8-benzyloxy-7-hydroxy-2-methyl-9-octadecene from which both enantiomers of disparlure, (7R,8S)-(+)-and (7S,8R)-(-)-7,8-epoxy-2-methyloctadecane, sex pheromone of the gypsy moth, were obtained in four and three steps, respectively.     

An Efficient Synthesis of Enantiomeric Ribonucleic Acids from D-Glucose

Enantiomeric oligoribonucleotides (= ent-RNA) up to a sequence length of thirty-five and consisting of the (L -configurated) nucleosides ent-adenosine, ent-guanosine, ent-cytidine, ent-uridine, and 1-(β-L -ribofuranosyl)thymine were prepared by automated synthesis from appropriate building blocks, carrying a known photo-labile 2′-O-protecting group. A simple large-scale synthesis of the new, prefunctionalized L -ribose derivative 5 from D -glucose (Scheme 1) and its straightforward conversion into the five phosphoramidites 28 – 32 and five solid supports 38 – 42 , respectively, were elaborated (Scheme 4). Within this project, a novel, superior strategy for the synthesis of the 2′-O-{[(2-nitrobenzyl)oxy]methyl}-substituted key intermediates 18 – 22 by regioselective alkylation of their 5′-O-dimethoxytritylated precursors 13 – 17 was developed. Furthermore, an improved set-up for the final light-induced cleavage of the 2′-O-protecting groups from the oligonucleotide sequences was designed (Scheme 5 and Fig. 1). The correct composition of all ent-oligoribonucleotides prepared was established by their MALDI-TOF mass spectra. The ¹H-NMR-spectroscopic data of a dodecameric ent-RNA sequence was in excellent agreement with the published data of its natural counterpart, synthesized by conventional methods. The known specific cleavage of a tetradecamer sequence by a 35mer ribozyme structure could be reproduced by ent-oligoribonucleotides, synthesized by the presented methods (Fig. 4).     

葡萄糖衍生的新型光学活性β－氨基醇的合成

首次报道了以Ｄ－葡萄糖为原料合成新型光学活性葡萄糖衍生类β－氨基醇化合物的新方法。目标化合物：（２Ｓ，３Ｓ）－甲基－２－脱氧－２－苯胺基－４，６－ｏ－苄叉基－α－Ｄ－吡喃阿卓糖苷（７）经各种分析测试手段证实。     

Pyrolysis of D-Glucose to Acrolein

Despite of its great importance, the detailed molecular mechanism for carbohydrate pyrolysis remains poorly understood. We perform a density functional study with a newly developed XYG3 functional on the processes for D-glucose pyrolysis to acrolein. The most feasible reaction pathway starts from an isomerization from D-glucose to D-fructose, which then undergoes a cyclic Grob fragmentation, followed by a concerted electrocyclic dehydration to yield acrolein. This mechanism can account for the known experimental results.     

A Novel Cyclic Carbamate from the Acid-Catalyzed Reaction of D-Glucose and Urea

Abstract

The acid-catalyzed reaction of D-glucose with urea in a phenol-water solution has provided α-D-glucopyranosylamine 1,2-(cyclic carbamate) (1). The use of ¹H-¹³C correlated NMR spectroscopy involving indirectly-bonded hydrogens and carbons proved to be indispensable in determining the structure.     

The Practical Asymmetric Syntheses of Key Chiral Intermediates of Chiral Drug from Four-Carbon Chiral Pool

(S)-or (R)-2-Amino-4-phenylbutyric acid and (S)-or (R)-2-hydroxy-4-phenylbutyric acid and their ethyl esters are key chiral intermediates for the preparation of angiotensin converting enzyme inhibitors (ACEI) and other chiral drugs. Their practically asymmetric synthetic methods in large scale from four-carbon chiral pool, commercially available L-aspartic acid and L-malic acid, will be presented (as scheme). (S)-2-Amino-4-phenylbutyric acid and its ethyl ester hydrochloride were prepared from the easily available L-aspartic acid via activation by forming anhydride hydrochloride, Friedel-Crafts reaction with benzene, hydrogenolysis and esterification with ethanol in the presence of thionyl chloride in overall yield of 80% and 73.6% respectively with 99% ee. We first used amino acid anhydride hydrochloride as the acylating agent in Friedel-Crafts reaction without racemization. [1]     

Carbasaccharides via Ring-Closing Alkene Metathesis. A Synthesis of (+)-Valienamine from D-Glucose

(+)-Valienamine ( 16 ) was prepared in seven steps and in an overall yield of 17% from commercially available 2,3,4,6-tetra-O-benzyl-D -glucopyranose. Stereoselective addition of vinylmagnesium bromide to the 1,3,4,5-tetra-O-benzyl-6,7-dideoxy-L -xylo-hept-6-en-2-ulose ( 2 ) gave diene 3 (86%). Ring-closing alkene metathesis of 3 in the presence of 0.15 equiv. of Grubb's catalyst 1 gave the cyclohexene 4 (58%), that was converted into (+)-valienamine ( 16 ) in three steps and in 47% yield. Similarly, ring-closing alkene metathesis of the D -mannose-derived diene 20 gave the cyclohexene 21 (89%).     

Synthesis of (2S,4S)-4-Hydroxyproline from D-Glucose

Diacetone-D-glucose 1 gives 3- O -methylxanthate 2 on reaction with NaH/Me I. Reductive deoxygenation of compound 2 by Bu₃SnH gives the corresponding 3-deoxy glucose derivative 3 and on acid-catalyzed regioselective deprotection of C-5,6-acetonide gives the diol 4. The diol on oxidative cleavage with NaIO₄ gives the aldehyde 5, which on further condensation with benzylamine followed by reduction with NaBH₄ gives the amine 7. Z-Protection of the amine followed by methanolysis gives methyl furanoside 9. Reaction of 9 with methanesulfonyl chloride/Et₃N gives the corresponding C-3-O-mesylate derivative 10. Catalytic hydrogenation of compound 10 (Pd/C/H₂/MeOH 3 kg) gives bicyclic oxaazo compound 11, due to deprotection of the N-benzyl- and Z-protecting groups and intramolecular nucleophilic displacement of the C-2- O-mesylate by the C-5 amine in a one-pot reaction. Z-Protection of the amine 11 followed by acid-catalyzed hydrolysis gives acetal 13. Reduction of acetal by use of NaBH₄ gives Z-prolinol 14. Selective oxidation of diol 14 by (2,2,6,6-tetramethylpiperidin-1-yl)-oxyl (TEMPO)/[(bis)(acetoxy)iodo]benzene (BAIB) and NaClO₂/NaH₂PO₄, followed by Z-deprotection, gives the title compound I in 3.5% overall yield from D-glucose.     

Synthesis and Chiral Recognition of Novel Chiral Macrocyclic Dioxopolyamines Derived from L-Proline

Recently, much concentration has been focused on chiral macrocyclic amides that bear the dual features of macrocyclic polyamines and oligopeptides, which can act as both hydrogen bond acceptors and donors and can form complexes with cation, anion or neutral molecules, so as to have potential applications for enantiomeric recognition and enantiomeric separation. In light that the more rigid the macrocyclic molecule, the better the enantiomeric recognition, and macrocyclic receptors possessing C2 symmetry usually show higher enantioselectivity than those of C1 symmetry, we chose L-proline, which possesses a unique and rigid pyrrolidinyl group, as starting material to synthesize a new class of novel chiral macrocyclic dioxopolyamines of C2 symmetry.     

手性配合物模板剂对磷酸锌骨架的手性传递

以外消旋的钴胺配合物Co(en)₃Cl₃为模板剂,在水热体系中合成出二种新颖的磷酸锌化合物:[Co(en)₃]·[Zn₈P₆O₂₄Cl]·2H₂O(1)和[Co(en)₃]₂·[Zn₆P₈O₃₂H₈](2     

Synthesis of Chiral Spiroacetals from Carbohydrates

Chiral spiroacetals of the 1,7-dioxaspiro[5.5]undecane, 1,6-dioxaspiro[4.5]decane, and 1,6-dioxaspiro[4.4]nonane types have been prepared from carbohydrates in pyranose or furanose forms. The spirocyclization reaction has been accomplished from a conveniently homologated carbohydrate by an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals. Thus, 2,3,4,6-tetra-O-benzyl-1-deoxy-1-(3'-hydroxypropyl)-alpha-D-glucopyranose (2) was photolyzed with visible light in the presence of (diacetoxyiodo)benzene and iodine to give a mixture of (1R)-(3) and (1S)-2,3,4,6-tetra-O-benzyl-1-deoxy-D-glucopyranose-1-spiro-2'-tetrahydrofuran (4). The photolysis of methyl 6-deoxy-6-(2'-hydroxyethyl)-2,3,4-tri-O-methyl-alpha-D-glucopyranoside (8) gave the isomeric spiroacetals methyl (5S)- (9) and (5R)-6-deoxy-5,2'-epoxy-6-ethyl-2,3,4-tri-O-methyl-alpha-D-glucopyranoside (10) in which the spirocenter is now located at C-5. The spiroacetals of the [5.5]undecane series: methyl (5R)- (19) and (5S)-6-deoxy-5,3'-epoxy-2,3,4-tri-O-methyl-6-propyl-beta-D-glucopyranoside (20) have been prepared starting from methyl 6-deoxy-6-(3'-hydroxypropyl)-2,3,4-tri-O-methyl-beta-D-glucopyranoside (18). The reaction has also been applied to hexofuranoses and 1-deoxy-1-(3'-hydroxypropyl)-2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranose (21) gave rise to (1S)- (22) and (1R)-1-deoxy-2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2'-tetrahydrofuran (23); and 1-deoxy-1-(4'-hydroxybutyl)-2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranose (28) to (1R)- (30) and (1S)-1-deoxy-2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2'-tetrahydropyran (32). Both spiroacetal enantiomers are formally available from the same carbohydrate.     

Syntheses of D-Myo-Inositol-1,2,6-Trisphosphate and -2,6-bisphosphate

Abstract

A D-myo-inositol derivative (3), obtained from methyl α-D-glucopyranoside by Ferrier rearrangement, was efficiently transformed to D-myo-inositol 1,2,6-trisphosphate (1, α-trinositol) and D-myo-inositol 2,6-bisphosphate (2).     

Chiral prostanoid intermediates from aucubin

Several potentially useful prostanoid intermediates have been prepared from aucubin. Dry DMSO-NBS converts enol ethers to α-bromoesters in one step.     

High-Performance Liquid Chromatographic Assay of D-Glucose in Erythrocytes

Abstract

A procedure is presented after several attempts with different modes of chromatography for measuring high concentrations of d-glucose in erythrocytes. The procedure utilizes rapid deproteinization of hemolysate by mixing with acetonitrile. The supernatant is analyzed by strong cation exchange chromatography, using an Organic Analysis Column. Separation conditions are: eluent = 0.01 N H₂SO₄, flow rate = 0.6 ml/min, detection = 195nm at 0.05 AUFS, sample size = 20 μl and temperature = ambient. The coefficients of variation for 5 mg/ml samples were (within-run) 6.7%, and (day-to-day) 7.1%. This study shows the presence of a high concentration (1900 mg/dl) of d-glucose within the erythrocytes as a result of a high external d-glucose concentration (2000 mg/dl) in plasma, and suggests that d-glucose is rapidly transported into the cell.