Enantioselective synthesis of 1-deoxy-d-gulonojirimycin from a phenylglycinol-derived lactam

Cyclocondensation of (R)-phenylglycinol with appropriately γ-substituted δ-oxo acid derivatives provides bicyclic lactams from which the enantioselective synthesis of 1-deoxy-d-gulonojirimycin has been reported.     

A new efficient and practical synthesis of 2-deoxy-l-ribose

An efficient and practical route for large-scale synthesis of 2-deoxy-l-ribose starting from l-ascorbic acid was developed in eight steps without chromatographic purification for all intermediates. Additionally, (2S,3R)-3,4-epoxy-1,2-O-isopropylidenebutane-1,2-diol, a versatile intermediate in carbohydrate synthesis, was also prepared readily in excellent yield as a key intermediate.     

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.     

Asymmetric synthesis of homo-apioneplanocin A from d-ribose

Homo-apioneplanocin A was efficiently synthesized via stereoselective hydroxymethylation, regio- and chemoselective hydroboration, and chemoselective oxidation as key steps from d-ribose.     

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 chemo-enzymatic cascade for the one-pot synthesis of 1-deoxy-d-xylulose 5-phosphate and 1-deoxy-d-xylulose

A chemo-enzymatic cascade for the one-pot preparation of 1-deoxy-d-xylulose 5-phosphate (DXP) and 1-deoxy-d-xylulose (DX) from stable, cheap, and easily available starting material R-glycidol is reported. The epoxide ring of R-glycidol was opened with phosphate to generate l-glycerol 3-phosphate, which was subsequently converted into the target molecules by combination of multi-enzymatic reactions in the same flask with purified overall yields of 27.6% (DXP) and 33% (DX), respectively. This approach represents the first one-pot chemo-enzymatic synthesis of these two biologically important compounds.     

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.     

Enantioselective synthesis of d- and l-α-methylcysteine with hydantoinase

A scalable and cost-effective synthesis of d- and l-α-methylcysteine is described. A key step is d-selective cyclization of N-carbamoyl S-tert-butyl-d,l-α-methylcysteine catalyzed by hydantoinase. d-5-tert-Butylthiomethyl-5-methylhydantoin and N-carbamoyl S-tert-butyl-l-α-methylcysteine were obtained with excellent yield and optical purity, and these compounds were easily separated by filtration. After hydrolysis and cleavage of the tert-butyl group, d- and l-α-methylcysteine hydrochloride were obtained.     

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.     

Chiral building blocks from d-xylose and their application in synthesis of avocadotriol monoacetate

Facile routes to several enantiomerically pure flexible chiral building blocks carrying a hidden syn or anti 1,3-diol motif were developed with the inexpensive and readily available carbohydrate d-xylose as the starting material. Application of the newly developed chiral building blocks in total synthesis is exemplified through a synthesis of (2S,4S)- and (2S,4R)-avocadotriol. Both triols were selectively acetylated on the primary hydroxyl group in high yields with Novozyme 435/vinyl acetate. On the basis of comparison of the ¹H NMR, optical rotation, and melting point data, the natural avocadotriol 1-monoacetate was assigned to be of (2R,4R) configuration.     

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.     

Asymmetric syntheses of the methyl glycosides of 2-deoxy-2-aminohexoses: d-allosamine, d-mannosamine, d-idosamine and d-talosamine

A range of the methyl glycosides of 2-deoxy-2-aminohexoses, comprising d-allosamine, d-mannosamine, d-idosamine and d-talosamine, were prepared from the corresponding d-aldopentoses via a seven step synthetic sequence. The doubly diastereoselective conjugate addition of the requisite antipode of lithium N-benzyl-N-(α-methylbenzyl)amide and in situ enolate oxidation with the requisite antipode of camphorsulfonyloxaziridine (CSO) was used as the key, stereodefining step. Sequential reduction of the resultant α-hydroxy-β-amino esters and oxidative cleavage of the C(1)–C(2) diol unit furnished the corresponding α-amino aldehydes. Subsequent N- and O-deprotection gave the target compounds (as mixtures of anomers) in good yield and high diastereoisomeric purity.     

Enantioselective total synthesis of (2S,3R,4R)-d-xylo-phytosphingosine from substituted azetidin-2-one

Enantiomerically pure (2S,3R,4R)-d-xylo phytosphingosine is synthesized in 36% overall yield in seven steps from known β-lactam (8) derived from d-mannitol triacetonide.     

A new and short synthesis of naturally occurring 1-deoxy-l-gulonojirimycin from tri-O-benzyl-d-glucal

A new and short synthesis of naturally occurring 1-deoxy-l-gulonojirimycin from tri-O-benzyl-d-glucal, via a regioselective intramolecular cyclization of an amino triol intermediate, is described. Its absolute configuration was deduced from the single crystal X-ray analysis of compound 11.     

Improved synthesis of 6-amino-6-deoxy-d-galactono-1,6-lactam and d-mannono-1,6-lactam from corresponding unprotected d-hexono-1,4-lactones

Regioselective bromination of unprotected d-galactono-1,4-lactone and d-mannono-1,4-lactone with PPh₃/CBr₄ led to 6-bromo-6-deoxy derivatives. These intermediates were treated with LiN₃ and hydrogenated to give 6-amino-6-deoxy-d-galactono-1,6-lactam (8) and 6-amino-6-deoxy-d-mannono-1,6-lactam (13) in 74 and 67% overall yield, respectively.     

First enantioselective synthesis of (−)-neplanocin F

(−)-Neplanocin F, the natural isomer of a component of the neplanocin family was enantioselectively synthesized starting from d-γ-ribonolactone. The synthetic approach was based on the preparation of a suitable carbocyclic precursor bearing three hydroxyl groups orthogonally protected. The key steps of the synthesis were the regioselective protection of a secondary allylic alcohol over a homoallylic one and the coupling of the nucleobase with a triflate intermediate.     

One-pot inversion of d-mannono-1,4-lactone for the practical synthesis of l-ribose

l-Ribose was synthesized in a concise manner from d-mannono-1,4-lactone using one-pot inversion conditions. Treatment of d-mannono-1,4-lactone with piperidine, followed by mesylation-induced S_N2-type O-alkylation, afforded the desired one-pot inversion in an optimum yield, and the following straightforward transformations provided l-ribose in good yields.     

Stereoselective synthesis of 3-glycosyl-5-methoxycarbonyl-isoxazolidines from d-galactose and d-glucose

Regio- and stereoselective cycloaddition of methyl acrylate to C-glycosyl nitrones derived from d-galactose and d-glucose, giving 5-methoxycarbonyl-3-(pentoglycos-5-yl or pentitol-1-yl)isoxazolidines, is reported. Transformation of one of them into a 4-hydroxy-2-(pentoglycos-5-yl)pyrrolidine derivative, potentially useful in a route to polyhydroxy-perhydroazaazulenes, was achieved.     

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.     

Total synthesis of (+)-galanthamine starting from d-glucose

The stereoselective total synthesis of (+)-galanthamine (+)-1 starting from d-glucose is described. The cyclohexene ring in (+)-1 was prepared in an optically active form from d-glucose using Ferrier’s carbocyclization reaction, and the critical quaternary carbon was stereoselectively generated via chirality transfer based on the Claisen rearrangement of a cyclohexenol. The dibenzofuran skeleton was effectively constructed by the bromonium ion-mediated intramolecular cyclization of a cyclohexene possessing a phenolic ether function. After the introduction of a carbon-carbon double bond, the Pictet-Spengler type cyclization, followed by the reduction of the amide function completed the chiral synthesis of (+)-1.