Synthesis of D-(6R) - and D-(6S) -(6-2H1) glucose

Chemical synthesis ofD-(6R)- and D(6S)-(6-²H₁) glucose is described comprising (i) formation of 6-²H₁)-3-o-benzyl-5,6-dideoxy-l, 2-0-isopropylidene-α-D-xylo-hex-5-ynofuranose from D-glucose; (ii) stereospecific reduction of the deuterated acetylene functionality to (E)- or (Z)-deuterated olefin; (iii) stereospecific cis-dihydroxylation of the deuterated olefin; and (iv) separation of stereoisomers based on the intrinsic chirality of D-glucose and subsequent deprotection.     

The first stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one

Iterative asymmetric allylations and ring-closing metathesis have been effectively performed for the first stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one, a novel α,β-unsaturated-δ-lactone having antifungal activity, isolated from Ravensara crassifolia.     

Synthesis of (E)-2-methoxy-6-(R-imino)methylphenols and 2-methoxy-6-(R-amino)methylphenols

(E)-2-Methoxy-6-(R-imino)methylphenols were synthesized by the condensation of 2-hydroxy-3-methoxybenzaldehyde with primary amines. By reduction of the iminophenols with sodium triacetoxyborohydride 2-methoxy-6-(R-amino)methylphenols were obtained.     

Stereoselective total synthesis of (+)-strictifolione and (6R)-6[(E,4R,6R)-4,6-dihydro-10-phenyl-1-decenyl)-5,6-dihydro-2H-2-pyrone

The stereoselective total synthesis of two naturally occurring α-pyrone derivatives, (+)-strictifolione and (6R)-6[(E,4R,6R)-4,6-dihydroxy-10-phenyl-1-decanyl]-5,6-dihydro-2H-2-pyrone has been accomplished involving the Sharpless kinetic resolution and olefin cross-metathesis as the key reactions.     

Enantioselective synthesis of (+)-(S)-7,8-dihydrokavain and (4R,6R)-4-hydroxy-6-(2-phenylethyl)tetrahydro-2H-pyran-2-one, lactone analog of compactin and mevinolin

A simple and efficient asymmetric synthesis was performed of (+)-(S)-7,8-dihydrokanian and (4R,6R)-4-hydroxy-6-(2-phenylethyl)tetrahydro-2H-pyran-2-one involving Keck allylation in the key stage of building up the carbon scaffold of the target molecules.     

First stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one

A stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one is reported. The strategy utilizes an iterative Jacobsen hydrolytic kinetic resolution, ring opening with a chiral propargylic synthon and a preferential (Z)-Wittig olefination reaction and lactonization as the key steps.     

Stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one by Prins reaction and olefin cross-metathesis

Prins and olefin cross-metathesis reactions were used as the key steps for the stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one. Removal of MOM protecting groups under neutral conditions using CeCl₃·7H₂O is an attractive addition to the present strategy.     

Efficient synthesis and resolution of novel 2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one by lipase Pseudomonas cepacia

Lipase Pseudomonas cepacia catalyzed acylation of (±)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one using vinyl acetate as the acyl donor in acetone gave (−)-(R)-2-acetoxy-2-(methyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one and (+)-(S)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one with high enantiomeric excess. Enantiomerically pure 2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one are useful intermediates for the preparation of Ramelteon, an FDA approved drug for the treatment of insomnia.     

Five-membered 2,3-dioxo heterocycles: CVI. Acylation of substituted (Z)-2-[1,3,4,4a,5,10b-Hexahydrophenanthridin-6(2H)-ylidene]acetamide with aroylketenes. crystal and molecular structure of substituted N-{(Z)-2-[1,3,4,4a,5,10b-Hexahydrophenanthridin-6(2H)-ylidene]acetyl}acrylamide

Aroylketenes generated by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with (Z)-2-[4a,7,10-trimethyl-1,3,4,4a,5,10b-hexahydrophenanthridin-6(2H)-ylidene]acetamide to give (Z)-3-aryl-3-hydroxy-N-{(Z)-2-[4a,7,10-trimethyl-1,3,4,4a,5,10b-hexahydrophenanthridin-6(2H)-ylidene]acetyl}acrylamides whose structure was confirmed by X-ray analysis.     

Collagen cross-links: a convenient synthesis of tert-butyl-(2S)-2-[(tert-butoxycarbonyl)amino]-4-(2-oxiranyl)butanoate

An efficient synthesis of tert-butyl-(2S)-2-[(tert-butoxycarbonyl)amino]-4-(2-oxiranyl) butanoate (5), the key intermediate for preparation of collagen cross-links (+)-pyridinoline (Pyd, 1) and (+)-deoxypyridinoline (Dpd, 2) was described from (4S)-5-(tert-butoxy)-4-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid (6) in six steps. Also, an improved synthesis of iodide (2S)-(−)-4b was presented.     

Synthesis of lithium,sodium, cesium,and calcium salts of (E)-4- or (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)-methyleneaminobutanoic, (E,S)-4-methyl-2- or (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic,and (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic acids

Preparative method for the synthesis of lithium, sodium, cesium, and calcium salts of (E)-4-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic, (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E,S)-4-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic and (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic acids was developed by reacting 5-phenyl(4-tolyl)isoxazole-3-carbaldehydes with amino acids like 4-aminobutyric and 6-aminocaproic acids, L-valine, L-leucine or L-isoleucine in the presence of lithium hydride, sodium methoxide, cesium carbonate or calcium hydride in boiling methanol.     

(R)- and (S)-N-(Benzyloxycarbonyl)-3,4-epoxybutylamine. New 4-amino-2-hydroxybutyl synthons for the synthesis of hypusine reagents and (R)-6- and (S)-7-hydroxyspermidine

The synthesis and application of the chiral reagents (R)- and (S)-N-(benzyloxycarbonyl)-3,4-epoxybutylamine is described for the first time. These 4-amino-2-hydroxybutyl synthons are successfully employed in the assembly of two hydroxylated triamines, (R)-6- and (S)-7-hydroxyspermidine, and a previously described hypusine reagent, (2S,9R)-11-[(benzyloxycarbonyl)amino]-7-(benzyloxycarbonyl)-2-[(9-fluorenylmethoxycarbonyl)amino]-9-(tetrahydropyran-2-yloxy)-7-azaundecanoic acid, useful for solution- and solid-phase peptide synthesis.     

Synthesis and tautomeric structure of 2-[N-aryl-2-oxo-2-arylethanehydrazonoyl]-6-methyl-4(3H)-pyrimidinones

Two series of 2-(N-aryl-2-oxo-2-arylethanehydrazonoyl)-6-methyl-4(3H)-pyrimidinones 11 (12) were prepared by coupling of diazotized anilines with 2-(aroylmethylene)-1,2-dihydro-6-methyl-4(3H)-pyrimidinones 2 (3). The spectral data of such compounds together with their 3-methyl analogs 13 (14) indicated that they exist predominantly in the hydrazone tautomeric form.     

Studies on the transformation of nitrosugars into iminosugars III: synthesis of (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol

A divergent synthesis of the two novel polyhydroxylated azepanes (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol from d-mannose is described. The method involves a Henry reaction between dimethyl-tert-butylsilyl 2,3-O-isopropylidene-α-d-lyxo-pentodialdo-1,4-furanoside and 2-nitroethanol followed by a reductive ring closure of the resulting epimeric nitro aldols. Glycosidase inhibition tests showed that (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol exhibits a weak but selective inhibition against α-l-fucosides.     

Asymmetric synthesis of 3-substituted 8-hydroxy-3,4-dihydroisocoumarins from (S)-4-isopropyl-2-(2-methoxy-6-methylphenyl)oxazoline

Reaction of the laterally lithiated (S)-4-isopropyl-2-(2-methoxy-6-methylphenyl)oxazoline with p-tolualdehyde gave an inseparable mixture of the addition products in low diastereoselectivity. However, the (S,S)-product cyclized to the corresponding 3,4-dihydroisocoumarin faster than the (S,R)-product on silica gel, which allowed to be produced both enantiomers of 8-methoxy-3-(p-tolyl)-3,4-dihydroisocoumarin in moderate to good optical purity [S-enantiomer: 75% ee; R-enantiomer: 96% ee]. This procedure was applied to the short-step synthesis of optically active 3,4-dihydroisocoumarin natural products such as (R)-8-hydroxy-3-(1-tridecyl)-3,4-dihydroisocoumarin and (R)-phyllodulcin.     

6-Chloro-2(2H)-pyranone: a new 2(2H)-pyranone synthon

6-Chloro-2(2H)-pyranone, which can be prepared in high yield from commercially available trans-glutaconic acid, undergoes facile Pd/Cu-catalyzed reaction with various 1-alkynes to give rise to the corresponding 6-(1-alkynyl)-2(2H)-pyranones in moderate to good yields. These last hitherto unknown compounds have been used as direct precursors to 6-alkyl- and 6-[(Z)-1-alkenyl]-2(2H)-pyranones.     

Preparation of dimethyl (R)- and (S)-2-(2-aminophenyl)-2-hydroxyethylphosphonate from anthranilic acid

An efficient synthesis of both enantiomers of dimethyl δ-amino-β-hydroxyethylphosphonate 6 has been achieved starting from anthranilic acid, through the resolution of dimethyl (±)-2-(2-N,N-dibenzylaminophenyl)-2-hydroxyethylphosphonate 9 with (S)-O-methylmandelic acid. The absolute configuration of the enantiomers 9 was assigned by the Dale and Mosher approach using the extended Newman projections and molecular mechanics.     

Synthesis and characterisation of [OC-6-33][OsCl2(CO)2L2] (L=phosphine). Crystal structure of [OC-6-33][OsCl2(CO)2(PEt3)2]

A series of [OC-6-33][OsCl₂(CO)₂L₂] (L=phosphine) complexes have been prepared by cleavage of [OsCl(μ-Cl)(CO)₃]₂ with a variety of phosphines for a comparison of spectroscopic data with those for the related [OC-6-13][OsF₂(CO)₂L₂] (L=phosphine). The X-ray structural characterisation of [OC-6-33][OsCl₂(CO)₂(PEt₃)₂] represents the first structural characterisation for this class of complex.     

Chemoenzymatic synthesis of (2R,6R,10R)-6,10,14-trimethylpentadecan-2-ol, sex pheromone of rice moth (Corcyra cephalonica), and of its (2S,6R,10R)-diastereomer

Based on the catalyzed by lipase Amano PS kinetic separation of the two-component mixture of diastereomers of (2RS,6R,10R)-6,10,14-trimethylpentadecan-2-ol in the acylation with the succinic anhydride we obtained the (2R,6R,10R)-6,10,14-trimethylpentadecan-2-ol, the sex pheromone of rice moth (Corcyra cephalonica) and its (2S,6R,10R)-diastereomer.