Total synthesis of natural cis-3-hydroxy-l-proline from d-glucose

Synthesis of cis-3-hydroxy-l-proline from d-glucose is reported. The methodology involves conversion of d-glucose into N-benzyloxycarbonyl-γ-alkenyl amine which on 5-endo-trig-aminomercuration gave the pyrrolidine ring skeleton with sugar appendage in 25% yield. Alternatively, N-benzyloxycarbonyl-γ-alkenyl amine on hydroboration-oxidation, mesylation and intramolecular S_N2 cyclisation afforded pyrrolidine ring compound in high yield. Hydrolysis of 1,2-acetonide functionality, NaIO₄ cleavage followed by oxidation of an aldehyde into acid and hydrogenolysis afforded cis-3-hydroxy-l-proline in overall 29% yield from d-glucose.     

Enantiodivergent total synthesis of microcarpalide from l-tartaric acid

Stereoselective approach for the synthesis of both enantiomers of bio-active decanolactone microcarpalide is described from l-tartaric acid. The synthesis of the key intermediates en route to the natural product is achieved from l-tartaric acid involving the elaboration of γ-hydroxy amide derived from tartaric acid and ring opening of an epoxide derived from tartaric acid.     

An efficient synthesis of d-ribo- and l-lyxo-phytosphingosine from d-tartaric acid

The preparations of d-ribo- and l-lyxo-phytosphingosines (1, 2) are described. Chelation-controlled addition of tetradecylmagnesium bromide to pentylidene-protected d-threitol aldehyde 6 afforded the key intermediate tetrol 7, providing the desired l-lyxo stereochemistry of phytosphingosine. Inversion at C4 of intermediate 7 provided the d-ribo stereochemistry.     

Practical synthesis of d-[1-C]mannose, l-[1-C] and l-[6-C]fucose

The chemical synthesis of ¹³C-labeled mannose and fucose is important for the preparation of molecular probes used in the conformational study of the oligosaccharide portions of glycoproteins. A new method for the synthesis of the title [1-¹³C]-labeled compounds via the corresponding olefin compounds, which are in turn derived from d-mannitol or l-arabinose by efficient introduction of ¹³C, by the Wittig reaction using Ph₃P¹³CH₃I and n-BuLi, is described. The introduction of ¹³CH₃I to produce the [1-¹³C]- and [6-¹³C]-labeled compounds was accomplished in 62%, 56%, and 71% yields, respectively. All mannose and fucose protons, from H-1 to H-6, were observed by the HMQC-TOCSY technique using 1:1 mixtures of [1-¹³C]- and [6-¹³C]-labeled compounds.     

Synthesis and characterization of polyamides obtained from tartaric acid and L-lysine

Two sets of AA · BB-type polyamides (PLyTA) were synthesized from natural compounds L-lysine and D- or L-tartaric acid via the active ester polycondensation method. The carboxyl and hydroxyl side groups were orthogonally protected as methyl ester and methyl ether, respectively. Direct reaction of methyl L-lysinate dihydrochloride with bis(pentachlorophenyl) di-O-methyl tartaric acid led to the aregic polyamide ar-PLyTA, whereas isoregic (ir-PLyTA) and syndioregic (sr-PLyTA) polyamides were obtained by polycondensation of specifically designed amide–aminoacid and amide–diamine monomeric precursors, respectively. These polyamides have intrinsic viscosities in the 0.50–0.76 dl g⁻¹ range, display optical activity, and are readily soluble in chloroform. They start to decompose well above 200 °C and display glass-transition temperatures at 100–105 °C. DSC and X-ray diffraction results indicated that these polyamides are not crystalline but they seem to adopt a partially ordered phase. No differences in properties other than optical rotation were observed between PLyTA made of D- and L-tartaric acid.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

Synthesis of l,l-puromycin

l,l-Puromycin, a diastereomer of the natural peptidyl nucleoside antibiotic puromycin, has been synthesized from l-xylose in 13 steps.     

From d-xylose to a d-glycero-l-altrose derivative

A key intermediate corresponding to a rare sugar framework has been synthesized, starting from d-xylose, an inexpensive carbohydrate. This approach gave access to new elaborated sugar moieties for structure–activity relationships in the KRN research.     

Synthesis of d-glucose and l-phenylalanine substituted phenylene-thiophene oligomers

Phenylene-thiophene oligomers bearing peracetylated β-d-glucose or N-BOC-l-phenylalanine as chiral substituents were synthesized in good yields by a versatile protocol based on the Suzuki-Miyaura cross-coupling reaction. Aryl iodides bearing the chiral biomolecules as substituents efficiently reacted with pinacol boronates of bi- or terthiophenes leading to the bio-functionalized oligomers in good yields.     

A convenient synthesis of l-ribose from d-fructose

An efficient method for the stereoselective synthesis of l-ribose was accomplished starting from commercially inexpensive d-fructose. The intermediates in the process can serve as versatile precursors for the preparation of l-nucleoside analogues.     

Synthesis of homochiral 2-C-perfluoroalkyl substituted d- and l-riboses

Homochiral 2-C-perfluoroalkyl substituted d- and l-riboses were synthesized via Barbier, Grignard and Ruppert type reactions. The influence of the size of the perfluoroalkyl groups, attached to C-2, on the furanose/pyranose as well as on the α-furanose/β-furanose and α-pyranose/β-pyranose ratio in solution was studied.     

Characterization and release of triptolide-loaded poly (d,l-lactic acid) nanoparticles

Triptolide (TP), which has immunosuppressive effect, anti-neoplastic activity, anti-fertility function and severe toxicities on digestive, urogenital, blood circulatory system, was used as a model drug in this study. TP-loaded poly (d,l-lactic acid) (PLA) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method). Dynamic light scattering system (DLS), transmission electron microscope (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray powder diffractometry and Fourier transform infra-red spectroscopy (FT-IR) were employed to characterize the nanoparticles fabricated for size and size distribution, surface morphology, the physical state of drug in nanoparticles, and the interaction between the drug and polymer. Encapsulation efficiency (EE) and the in vitro release of TP in nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC). The produced nanoparticles exhibited a narrow size distribution with a mean size of approximately 150 nm and polydispersity index of 0.088. The morphology of the nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion. TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline. It was found that a weak interaction existed between the drug and polymer. In all experiments, more than 65% of EE were obtained. The in vitro release profile of TP from nanoparticles exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. In this case, the particle size played an important role for the drug release. The modified-SESD method was a potential and advantage method to produce an ideal polymer nanoparticles for drug delivery system (DDS).     

A facile synthesis of 1,4-dideoxy-1,4-imino-l-ribitol (LRB) and (−)-8a-epi-swainsonine from d-glutamic acid

A facile synthesis of (−)-8a-epi-swainsonine 2 and 1,4-dideoxy-1,4-imino-l-ribitol (LRB) 4 has been achieved by using the versatile building block 3, which was available from cheap d-glutamic acid. The new forming stereogenic center in synthesis of 2 was constructed by highly selective reduction of the ketone 13 with Li(t-BuO)₃AlH in THF (dr=95:5).     

Sulfonate protecting groups. Synthesis of O- and C-methylated inositols: d- and l-ononitol, d- and l-laminitol, mytilitol and scyllo-inositol methyl ether

Syntheses of d- and l-ononitol, d- and l-laminitol, mytilitol and scyllo-inositol methyl ether starting from myo-inositol are described. One or two of the myo-inositol 1,3,5-orthoformate hydroxyl groups were protected as tosylates. These mono or ditosylates served as key intermediates for the preparation of O- and C-methyl inositols. Racemic 2,4-di-O-tosyl-myo-inositol 1,3,5-orthoformate was resolved as its diastereomeric camphanates. Use of sulfonate groups for the protection of inositol hydroxyl groups resulted in substantial improvement in the overall yield of O- and C-methyl inositols.     

Synthesis of l-aminohomohistidine (l-Ahh)

A short synthesis of l-aminohomohistidine (l-Ahh), which starts from readily available δ-hydroxy-l-lysine is described. The embedding of the basic guanidino moiety in the aromatic imidazole lowers the basicity of the side chain to a pK_a of 8.3. It is proposed that l-Ahh may be employed as an arginine-mimetic in medicinal chemistry.     

Asymmetric syntheses of 6-deoxyfagomin, d-deoxyrhamnojirimycin, and d-rhamnono-1,5-lactam

N-Allyl protected 3-O-benzyloxglutarimide 11 was synthesized as a useful variant of the chiral building block 10. This modification allowed a high-yielding deprotection of the allyl group from the lactam intermediate 14. Starting from this building block, the asymmetric syntheses of aza-sugars 6-deoxyfagomine (2), d-rhamnono-1,5-lactam (6), as well as d-deoxyrhamnojirimycin (5) have been achieved in high regio- and/or diastereo-controlled manner.     

A highly efficient synthesis of unnatural l-sugars from d-ribose

A preparative and short synthesis of l-ribose and l-apiose was accomplished starting from d-ribose via stereoselective cis-dihydroxylation and C2-hydroxymethylation, respectively. These l-sugars can serve as versatile intermediates for the synthesis of l-nucleosides.     

A convenient approach to total synthesis of synargentolide-B from l-ascorbic acid and d-ribose

A convenient and practical approach for the total synthesis of naturally occurring lactone synargentolide-B has been accomplished in 14 steps from the commercially available l-ascorbic acid and d-ribose involving Bestmann–Ohira reaction, zinc mediated allylation, ring closing-metathesis, and cross-metathesis reactions. The highlight of our strategy describes a one-pot reaction involving stereoselective addition of allylzinc reagent and selective reduction of terminal alkyne to obtain the key advanced intermediates.     

Swelling and hydrolytic degradation of poly(d,l-lactic acid) in aqueous solutions

Low molecular weight poly(lactic acid) was synthesized by direct polycondensation of lactic acid. The oligomers were characterized by viscometry, light scattering, and gel permeation chromatography (GPC). The swelling behaviour of tablets made of the above polymer immersed in buffer solutions at 37 °C was studied. In the same experiments, the hydrolytic stability of d,l-PLA was assessed by measuring the weight loss after drying the tablets. In order to inhibit any degradation due to bacteria, formaldehyde was added in the solution as biostatic factor. The effect of an incorporated drug on the swelling behaviour of d,l-PLA tablets was also considered. It was found that the incorporation of drug in d,l-PLA tablets increases their swelling index, probably due to the creation of additional porosity in the specimens or other interaction between drug and polymeric matrix.     

Synthesis of 1,4-dideoxy-1,4-imino-derivatives of d-allitol, l-allitol and d-talitol: a stereo selective approach for azasugars

A stereo selective approach for the azasugars 1,4-dideoxy-1,4-imino-d-allitol, l-allitol, and 1,4-dideoxy-1,4-imino-d-talitol is described for different olefin compounds I derived from (R)-2,3-O-isopropylidine glyceraldehyde, l-ascorbic acid, and d-isoascorbic acid by using vinyl Grignard addition, allylation, RCM, and dihydroxylation as the key steps.