Synthesis of (−)-lentiginosine, its 8a-epimer and dihydroxylated pyrrolizidine alkaloid from d-glucose

The d-glucose derived α,β-unsaturated ester 5 on 1,2-acetonide deprotection, oxidative diol cleavage followed by treatment with N-benzylamine in the presence of NaBH₃CN undergoes reductive amination and a concomitant intramolecular conjugate addition reaction leading to the formation of dihydroxypyrrolidine-ester 6a and monohydroxypyrrolidine-γ-lactone 6b. Intermediates 6a and 6b were efficiently converted to (−)-lentiginosine 3a, its 8a-epimer 3b, and pyrrolizidine azasugar 4 in good overall yield.     

Total synthesis of (−)-microcarpalide from d-mannitol

The total synthesis of the actin-targeting metabolite (−)-microcarpalide is described. Ring-closing metathesis of a dienic ester was used as the key step. d-Mannitol was used as the chiral pool material for the construction of the olefinic acid moiety as well as the olefinic alcohol moiety of the molecule.     

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.     

A concise synthesis of 2,5-dideoxy-2,5-imino-d-mannitol (DMDP) and HomoDMDP from l-xylose

A short and practical procedure for the preparation of C-2 substituted polyhydroxypyrrolidines is described. The C-2 substituent is introduced by a stereoselective addition of a Grignard reagent to a 2,3,5-protected aldofuranose and the cyclization to the pyrrolidine ring system is performed through a bis-mesylation/double nucleophilic displacement sequence. The efficiency of the methodology was demonstrated by its application to the synthesis of HomoDMDP and DMDP.     

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.     

Stereoselective total synthesis of (−)-synrotolide diacetate from d-ribose

Stereoselective total synthesis of synrotolide as its diacetate from d-ribose utilizing a diastereoselective Grignard reaction, preferential (Z)-Wittig olefination, asymmetric allylation, and ring closing metathesis as key steps is reported.     

Stereoselective total synthesis of (−)-decarestrictine D from l-malic acid

A convergent stereoselective total synthesis of (−)-decarestrictine D from l-malic acid is reported.     

A concise total synthesis of (+)-deoxocassine and (−)-deoxoprosophylline from d-xylose

A concise total synthesis of (+)-deoxocassine (1) and (−)-deoxoprosophylline (2) has been achieved for the first time from d-xylose. The key steps involved in these synthesis are alkyl Grignard reaction, S_N2 substitution of mesylate by azide, Wittig reaction, and reductive amination.     

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.     

De novo approach to l-anhydrohexitol nucleosides as building blocks for the synthesis of l-hexitol nucleic acids (l-HNA)

A stereoselective and scalable route to 1,5-anhydrohexitol nucleoside analogues belonging to l-series as building blocks for l-HNA oligonucleotide synthesis has been efficiently tuned. Key to the successful outcome of our approach is the development of a DDQ-mediated domino reaction, which leads to the formation of an unsaturated 1,6-anhydrosugar derivative. Sugar elaborations and base insertion then enable to synthesize six-membered nucleosides.     

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.     

Hydrolytic degradation of carbohydrate-based polyamides of the AABB type derived from l-arabinose and d-xylose

The hydrolytic degradation of a series of aregic carbohydrate-based polyamides derived from l-arabinose and d-xylose is described. These polyamides are those that are fully sugar-based (PA-SuSu), those derived from aldaric acids and polyalkylene diamines (PA-mSu), and those derived from diamine sugars and polyalkylene dicarboxylic acids (PA-Sun). Their physical properties and crystal structures depend on their constitution and the configuration of the carbohydrate-based moiety. The feasibility of the hydrolysis of these polyamides was, in general, related with such structural properties. Thus, the fully sugar-based PA-SuSu were amorphous, water-soluble materials, and were hydrolysed in water at 70 °C. PA-mSu were crystalline and more resistant to hydrolysis — they were degraded at pH 2 and 70 °C [T_g(s) 60-90 °C]. PA-Sun were amorphous and highly hygroscopic materials — they were hydrolysed in water at 37 °C [T_g(s) 25-40 °C].     

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.     

d- and l-Erythrose as sources of chiral quaternary carbon centers. Total synthesis of (−)-malyngolide and (+)-tanikolide

A highly efficient and versatile approach was applied for the total synthesis of the marine natural products (−)-malyngolide and (+)-tanikolide from isopropylidene l- and d-erythrose, using a common strategy.     

Total synthesis of d-(+)-biotin

A total synthesis of d-(+)-biotin is described starting from d-(+)-glucosamine using acyliminium chemistry.     

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.     

Stereoselective synthesis of l-isonucleosides

l-Isonucleosides 17 and 19 were stereoselectively synthesised from (S)-glycidol by two different procedures. The key step was the synthesis of a chiral dihydrofuran which was carried out by oxidation/elimination of 8 and by ring-closing metathesis of diene 10. The procedure can be applied to the synthesis of both enantiomers.     

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.     

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.     

Electrospun poly(l-lactide)-grafted hydroxyapatite/poly(l-lactide) nanocomposite fibers

Composite fibers composed of poly(l-lactide)-grafted hydroxyapatite (PLA-g-HAP) nanoparticles and polylactide (PLA) matrix were prepared by electro-spinning. Environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM) were employed to investigate the morphology of the composite fibers and the distribution of PLA-g-HAP nanoparticles in the fibers, respectively. At a low content (∼4 wt%) of PLA-g-HAP, the nanoparticles dispersed uniformly in the fibers and the composite fibrous mats exhibited higher strength properties, compared with the pristine PLA fiber mats and the simple hydroxyapatite/PLA blend fiber mats. But when the content of PLA-g-HAP further increased, the nanoparticles began to aggregate, which resulted in the deterioration of the mechanical properties of the composite fiber mats. The degradation behaviors of the composite fiber mats were closely related to the content of PLA-g-HAP. At a low PLA-g-HAP content, degradation may be delayed due to the reduction of autocatalytic degradation of PLA. When PLA-g-HAP content was high, degradation rate increased because of the enhanced wettability of the composite fibers and the escape of the nanoparticles from fiber surfaces during incubation.