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.     

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.     

Kiliani on ketoses: branched carbohydrate building blocks from d-fructose and l-sorbose

Protected branched sugar lactones are available via Kiliani-acetonation sequences on readily available ketoses such as d-fructose and l-sorbose. In both cases, the readily crystallized diacetonides have a 2,3-cis-diol relationship in the product lactone. An efficient double inversion of the configuration at C-4 and C-5 of the product from d-fructose gives access to the formal Kiliani product from l-psicose. Branched carbohydrate lactones are likely to be of significant value as chirons for homochiral targets with functionalized quaternary centres.     

Synthesis of (+)-amberketal and its analog from l-abietic acid

(+)-Amberketal (1) and its analog (2) have been synthesized from commercially available l-abietic acid (3) by a selective reduction of an unsaturated aldehyde in the presence of a ketone and simultaneous reduction of an iodide using an aqueous suspension of Raney Ni as the key step.     

Intermolecular/interionic interactions in l-isoleucine-, l-proline-, and l-glutamine-aqueous electrolyte systems

Speed of sound and density values for ternary systems (amino acid + salt + water): l-isoleucine/l-proline/l-glutamine in aqueous solutions of 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ have been measured for several concentrations of amino acids at different temperatures (303.15, 308.15, 313.15, 318.15, and 323.15 K). Using speed of sound and density data, the thermodynamic parameters such as isentropic compressibility (κ_s), change in isentropic compressibility (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility have been computed. The isentropic compressibility values decrease with increase in the amino acid concentration as well as with temperature. The decrease in κ_s values with increase in concentration of l-isoleucine/l-proline/l-glutamine in 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ has been ascribed to an increase in the number of incompressible zwitterions in solutions, and the formation of ‘zwitterions-ions’ and ‘zwitterions-water dipole’ entities in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax (a relaxational part of compressibility), which is dominant over the corresponding increase of κ_∞ (an instantaneous part of compressibility). The trends of variation of Δκ_s and Δκ_s/κ₀ with variations in solute concentration and temperature have also been discussed in terms of solute-solute and solute-solvent intermolecular/interionic interactions operative in the systems.     

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.     

Racemization behavior of l,l-lactide during heating

To control the depolymerization process of poly(l-lactic acid) into l,l-lactide for feedstock recycling, the racemization of l,l-lactide as a post-depolymerization reaction was investigated. In the absence of a catalyst, the conversion to meso-lactide increased with increase in the heating temperature and time at a higher rate than the conversion into oligomers. The resulting high composition of meso-lactide suggests that the direct racemization of l,l-lactide had occurred in addition to the known racemization mechanism that occurs on the oligomer chains. In the presence of MgO, the oligomerization rapidly proceeded to reach an equilibrium state between monomers and oligomers. The equilibrium among l,l-, meso-, and d,d-lactides was found to be a convergent composition ratio l,l-:meso-:d,d-lactides = 1:1.22:0.99 (wt/wt/wt) after 120 min at 300 °C. This composition ratio also indicates that in addition to the known racemization reaction on the oligomer chains, direct racemization among the lactides is also a frequent occurrence.     

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 1-deoxy-l-gulonojirimycin and 1-deoxy-l-talonojirimycin

De novo synthesis of noncompetitive glycosidase inhibitors l-gulo-DNJ and l-talo-DNJ has been achieved in 9-10 steps starting from Garner’s aldehyde. Key to the success of this procedure was the construction of the 2,3-unsaturated piperidine 14, which syn dihydroxylation under Kishi’s and Donohoe’s conditions led to the desired iminosugars.     

Stereoselective total synthesis of (+)-cardiobutanolide and (+)-3-epi-cardiobutanolide from diacetone d-glucose

A chiron approach starting with 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-pentodialdo-1,4-furanose utilizing a Grignard reaction, Mitsunobu stereoinversion, ethyl diazoacetate addition, and selective reduction of the ketone is employed as a key step for the total synthesis of (+)-cardiobutanolide described; a similar strategy is also reported for the first total synthesis of (+)-3-epi-cardiobutanolide.     

A common approach to the total synthesis of l-arabino-, l-ribo-C18-phytosphingosines, ent-2-epi-jaspine B and 3-epi-jaspine B from d-mannose

A common strategy for the total syntheses of the protected l-arabino- and l-ribo-C₁₈-phytosphingosine (8 and 9, respectively), HCl salts of ent-2-epi-jaspine B (ent-6) and 3-epi-jaspine B (7) with efficient use of both flexible building blocks 26 and 27 was achieved. The key step of this approach was [3,3]-sigmatropic rearrangement of allylic trichloroacetimidate 21 and thiocyanate 22, which were derived from the known 2,3:5,6-di-O-isopropylidene-d-mannofuranose 18 as the source of chirality. The side chain functionality was installed utilizing a Wittig reaction.     

Synthesis of d-gluco-, l-ido-, d-galacto-, and l-altro-configured glycaro-1,5-lactams from tartaric acid

The d-gluco-, l-ido-, d-galacto-, and l-altro-configured glycaro-1,5-lactams 1-4 were prepared from the known tartaric anhydride 5 via the aldehyde 6. These lactams are known (1) or potential (2-4) inhibitors of β-d-glucuronidases and α-l-iduronidases. Olefination of 6 to the (E)- and (Z)-alkenes 7 or 8, followed by reagent or substrate controlled dihydroxylation, lactonization, azidation, reduction, and deprotection led in 10 steps and in overall yields of 11-20% to the title lactams.     

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.     

Synthesis of l-3-epi-isofagomine,its homo-, n-butyl and bicyclic analogues from d-glucose as glycosidase inhibitors

Synthesis of l-3-epi-isofagomine, its homo-, n-butyl derivatives and its bicyclic analogue as potent glycosidase inhibitor has been achieved from readily available d-glucose. Inhibition of some commercially available glycosidases was also carried out with the newly synthesized inhibitors which showed reasonably good inhibitions (9.4–198.2 μM). One of them (compound 11) showed selective inhibition of β-galactosidase.     

Large scale synthesis of the acetonides of l-glucuronolactone and of l-glucose: easy access to l-sugar chirons

1,2-O-Isopropylidene-α-l-glucurono-3,6-lactone may be synthesized on a 100-200 g scale from cheaply available d-glucoheptonolactone in an overall yield of 94% in four steps via l-glucuronolactone. Subsequent elaboration to l-glucose, diacetone-l-glucose (1,2:5,6-di-O-isopropylidene-α-l-glucofuranose), and monoacetone-l-glucose (1,2-O-isopropylidene-α-l-glucofuranose) allows easy access to a range of l-sugar chirons.     

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.     

Phase behavior of biodegradable amphiphilic poly(l,l-lactide)-b-poly(ethylene glycol)-b-poly(l,l-lactide)

This study describes the miscibility phase behavior in two series of biodegradable triblock copolymers, poly(l-lactide)-block-poly(ethylene glycol)-block-poly(l-lactide) (PLLA-PEG-PLLA), prepared from two di-hydroxy-terminated PEG prepolymers (M_n = 4000 or 600 g mol⁻¹) with different lengths of poly(l-lactide) segments (polymerization degree, DP = 1.2-145.6). The prepared block copolymers presented wide range of molecular weights (800-25,000 g mol⁻¹) and compositions (16-80 wt.% of PEG). The copolymer multiphases coexistance and interaction were evaluated by DSC and TGA. The copolymers presented a dual stage thermal degradation and decreased thermal stability compared to PEG homopolymers. In addition, DSC analyses allowed the observation of multiphase separation; the melting temperature, T_m, of PLLA and PEG phases depended on the relative segment lengths and the only observed glass transition temperature (T_g) in copolymers indicated miscibility in the amorphous phase.     

Synthesis of l-arabinopyranose containing hederagenin saponins

The synthesis of eight hederagenin saponins, five of which are natural products, and their methyl esters is described as part of an ongoing study of the biological activity of triterpenoid saponins. Six disaccharides consisting of an l-arabinopyranose glycosylated in positions 2, 3, or 4 with a β-d-xylopyranose or a β-d-glucopyranose residue, respectively, were synthesized in good to excellent yields. The saponins were then prepared in good yields through glycosylation with a suitably protected hederagenin derivative followed by total deprotection and treatment with diazomethane.     

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.