The Structure of N‐(1‐Deoxy‐β‐D‐fructopyranos‐1‐yl)‐L‐proline Monohydrate (“D‐Fructose‐L‐proline”) and N‐(1,6‐Dideoxy‐α‐L‐fructofuranos‐1‐yl)‐L‐proline (“L‐Rhamnulose‐L‐proline”)

Nano n-propylsulfonated γ-Fe₂O₃ was found to be a highly efficient, reusable heterogeneous catalyst for the conversion of a range of monosaccharides and some of their derivatives to the corresponding O-isopropylidene derivatives in good to excellent yields by refluxing the reaction mixture in dry acetone. The magnetic property of the catalyst enabled its separation from the reaction mixture by a simple process of filtration along with the aid of an external magnet. The efficiency of the catalyst was found to be largely unaffected for at least up to six cycles of reuse, thus proving the new methodology to be environmentally rewarding besides being simple and facile in operation.     

Synthesis of Analogues of (1 → 6)‐Branched (1 → 3)‐Glucohexaose

Abstract

β‐D‐Galp‐(1 → 3)‐[β‐D‐Galp‐(1 → 6)‐]α‐D‐Glcp‐(1 → 3)‐β‐D‐Glcp‐(1 → 3)‐[α‐D‐Manp‐(1 → 6)‐]D‐Glcp 16 and β‐D‐Galp‐(1 → 3)‐[β‐D‐Glcp‐(1 → 6)‐]α‐D‐Glcp‐(1 → 3)‐β‐D‐Glcp‐(1 → 3)‐[α‐D‐Manp‐(1 → 6)‐]D‐Glcp 18 were synthesized as the analogues of the immunomodulator β‐D‐Glcp‐(1 → 3)‐[β‐D‐Glcp‐(1 → 6)‐]α‐D‐Glcp‐(1 → 3)‐β‐D‐Glcp‐(1 → 3)‐[β‐D‐Glcp‐(1 → 6)‐]D‐Glcp through coupling of trisaccharide donors 8 and 13 with trisaccharide acceptor 14 followed by deprotection, respectively.     

Studies Towards the Synthesis of the β‐D‐Xyl‐(1 → 3)‐L‐ara Disaccharide Moiety of OSW‐1 from Ornithogalum saundersiae

Abstract

The OSW‐1 disaccharide having 2‐O‐p‐methoxybenzoyl‐β‐D‐xylopyranosyl‐(1 → 3)‐L‐arabinopyranoside structure was obtained as the benzylated 4‐O‐acetyl derivative 19. Also, the 4,2′‐di‐O‐acetate 18 was synthesized by a short synthetic approach. The arabinose acceptor 15 was obtained in a three step‐one pot sequence from easily available benzyl β‐L‐arabinopyranoside.     

Synthesis of Acylated Methyl 2‐Acetamido‐2‐Deoxy‐α‐D‐Mannopyranosides

Abstract

2‐Acetamido‐2‐deoxy‐β‐D‐mannopyranose (1) was glycosylated by the Fischer method using an acidic ion‐exchange resin as the catalyst to give α‐methyl glycoside 2. Selective pivaloylations of methyl 2‐acetamido‐2‐deoxy‐α‐D‐mannopyranoside (2) have been studied under various reaction conditions. Two partially pivaloylated products were submitted to additional acetylations. All structures were established by NMR spectroscopy. Structure of the methyl 2‐acetamido‐2‐deoxy‐3,6‐di‐O‐pivaloyl‐α‐D‐mannopyranoside (4) was determined by X‐ray analysis.     

Novel C‐Thionucleosides: Synthesis and Reactions of 1,5‐ and 1,3‐Dialkyl Derivatives of (1,5‐Dithio‐1‐thiomethyl‐α‐D,L‐arabinopentulo‐pyranos‐1‐yl)‐1H‐1,2,4‐triazole Nucleosides

Abstract

A series of novel C‐thionucleosides: 1,5‐ and 1,3‐dialkyl derivatives of (2,3,4,5‐tetra‐O‐acetyl‐1,5‐dithio‐1‐methylthio‐α‐D,L‐arabinopentulopyranos‐1‐yl)‐1H‐1,2,4‐triazole nucleosides 10a–d and 17a–c were synthesized, after spontaneous rearrangements, from concerted 1,3‐cycloaddition of the sugar nitrile 5 with the reactive 1‐(chloroalkyl)‐1‐aza‐2‐azoniaallenes 6 and 13 in the presence of a Lewis acid. Deblocking of the acylated nucleosides afforded the free nucleosides 11a–d and 18a–c. The structures of the synthesized compounds were confirmed by ¹H NMR and mass spectra.     

Synthesis of Tetra‐O‐acetyl‐1‐thio‐α‐d‐glucopyranose by Reaction of Tetra‐O‐acetyl‐α‐d‐glucopyranosyl Bromide with N,N‐Dimethylthioformamide

A reaction system was found to prepare tetra‐O‐acetyl‐1‐thio‐d‐glycopyranose in both α and β‐forms. Methanolysis of the adduct prepared from the reaction of tetra‐O‐acetyl‐α‐d‐glucopyranosyl bromide with N,N‐dimethylthioformamide afforded the corresponding tetra‐O‐acetyl‐1‐thio‐d‐glucopyranose with an anomer ratio α/β of 52:48 in 98% yield. The anomer mixture was easily separated by column chromatography to obtain the product of α‐form. This synthetic method is very convenient to proceed by one‐pot reaction under ordinary conditions.     

Alternative Route for the Synthesis of 6‐Methoxy‐5‐methyl‐α‐tetralone and 6‐Methoxy‐2,5‐dimethyl‐α‐tetralone

The ketoesters 3 and 4, obtained by the condensation of 2‐cyclohexanone carboxylate and 1‐chloro‐3‐pentanone, were heated with 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ) to yield the dienones 5 and 6, which on hydrolysis with potassium t‐butoxide and dimethyl sulfoxide afforded tetralin 8. These were converted to tetralone 10 by methylation and oxidation respectively. Further methylation of 10 yielded tetralone 11.     

Synthesis of the C‐Glycoside of Methyl α‐d‐Altropyranosyl‐(1→4)‐α‐d‐glucopyranoside

The C‐glycoside of methyl α‐d‐altropyranosyl‐(1→4)‐α‐d‐glucopyranoside 2 was prepared in a convergent fashion, from readily available precursors, 4‐O‐tert‐butyldiphenylsilyl‐1,2‐O‐isopropylidene‐d‐erythro‐S‐phenyl monothiohemiacetal 13 (five steps from D‐ribose) and the known acid, methyl 2,3,6‐tri‐O‐benzyl‐4‐C‐(carboxymethyl)‐4‐deoxy‐α‐d‐glucopyranoside 17 (seven steps from methyl α‐d‐glucopyranoside). The key reactions in the synthesis are the oxocarbenium ion cyclization of thioacetal‐enol ether 19 to a C1 substituted glycal 20, and the stereoselective hydroboration of 20 to the α‐C‐altroside 21.     

Practical Preparation of Z‐α‐(N‐Acetylamino)‐ and Z‐α‐(N‐Benzoylamino)‐α,β‐unsaturated Acids

An efficient two‐step synthetic procedure for the preparation of numerous variations of N‐protected α,β‐unsaturated α‐amino acids and their corresponding esters from N‐protected glycine and either aliphatic or aromatic aldehydes was developed. The reaction involved cyclization of the N‐protected glycine into oxazolone, condensation with the aldehyde, and ring opening with a base.     

Cesium Carbonate–Promoted Michael‐Type Addition of Thiols to Hex‐1‐en‐3‐ulose: A Practical Synthesis of 2‐Deoxy‐1‐thio‐α‐hexopyranosid‐3‐ulose Template

The template 2‐deoxy‐1‐thio‐α‐hexopyranosid‐3‐ulose was synthesized in quantitative yield and high diastereoselectivity by 1,4‐addition of aryl and alkyl thiols to hex‐1‐en‐3‐ulose promoted by cesium carbonate in THF.     

Synthesis of C‐Nucleoside Analogues Starting from 1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one

Abstract

1‐(Methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐4‐phenyl‐but‐3‐yn‐2‐one (4) was synthesized by the reaction of (methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)ethanal (2) with lithium phenylethynide and following oxidation. Compound 4 and hydrazine hydrate provided the 3(5)‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl‐methyl)‐5(3)‐phenyl‐1H‐pyrazole (5). The reactions of 4 with amidinium salts and a S‐methyl‐isothiouronium salt, respectively, furnished the pyrimidine C‐nucleoside analogues 6a–6c. Treatment of 4 with 2‐aminobenzimidazole afforded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐ylmethyl)‐4‐phenyl‐benzo [4,5]imidazo[1,2‐a]pyrimidine (7a). Compound 4 and sodium azide yielded 2‐(methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐α‐D‐altropyranosid‐2‐yl)‐1‐[5(4)‐phenyl‐1H(2H)‐1,2,3‐triazole‐4(5)‐yl]ethanone (8).     

Reductive Ring‐Opening Reaction of 1,2‐O‐Benzylidene and 1,2‐O‐p‐Methoxybenzylidene‐α‐D‐glucopyranose Using Diisobutyl Aluminum Hydride

Abstract

Regioselectivity in the reductive ring‐opening reaction of 3,4,6‐tri‐O‐benzyl‐1,2‐O‐benzylidene and 3,4,6‐tri‐O‐benzyl‐1,2‐O‐p‐methoxybenzylidene‐α‐D‐glucopyranose using diisobutyl aluminum hydride (DIBAH) was examined. The ratio of the 1‐O‐ and 2‐O‐p‐methoxybenzyl ethers, which were generated from endo‐type 1,2‐O‐p‐methoxybenzylidene, was variable by the change of solvent.     

Sucrosyl‐(1 → 2)‐β‐Isomaltulose: Enzymatic Synthesis and Structure Determination

Abstract

By enzymatic reaction of sucrose (1) and isomelezitose (2) with the enzyme inulinase (NOVO, SP230) a novel tetrasaccharide (3) was synthesised,.the molecular weight of which was confirmed by electrospray‐ionisation mass spectrometry and gel permeation chromatography. Its structure was established by acid hydrolysis as well as ¹H and ¹³C NMR spectroscopy to be sucrosyl‐(1 → 2)‐β‐isomaltulose 3 (α‐D‐glucopyranosyl‐(1 → 2)‐β‐D‐fructofuranosyl‐(1 → 2)‐β‐D‐fructofuranosyl‐(6 → 1)‐α‐D‐glucopyranoside).     

Synthesis of C‐Glycosyl Phosphate and Phosphonate,Analogues of N‐Acetyl‐α‐d‐Glucosamine 1‐Phosphate

Synthesis of α‐C‐ethylene phosphate and phosphonate as well as α‐C‐methylene phosphate analogues of N‐acetyl‐α‐d‐glucosamine 1‐phosphate is reported starting from the common perbenzylated 2‐acetamido‐2‐deoxy‐α‐C‐allyl glucoside. Anomerisation of the corresponding amino α‐C‐glucosyl aldehyde to the β‐aldehyde was observed. Thus, both amino α‐ and β‐C‐glucosyl methanol were obtained after reduction.     

Synthesis of Substituted 1‐\C\‐Phenyl‐D‐Tetritols and 1‐C‐(1H‐Pyrazol‐4‐yl)‐D‐tetritols by Ring Transformation of 2‐Formylglycals

Abstract

2‐Formylglycals 1a,b reacted with dialkyl 3‐oxoglutarates in the presence of base to furnish the 5‐[(1R,2R(S),3R)‐1,2,4‐tris(benzyloxy)‐3‐hydroxy‐butyl]‐2‐hydroxy‐isophthalic acid dialkyl esters 2a–d. Treatment of 1a,b with hydrazine derivatives afforded the substituted 1,2,4‐tri‐O‐benzyl‐1C‐(1H‐pyrazol‐4‐yl)‐D‐tetritols 5a–d. Deprotection of 5a,b was achieved with Pd/H₂ to yield the 1C‐(1‐methyl‐1H‐pyrazol‐4‐yl)‐D‐tetritols 6a,b.     

Synthesis of 7‐Alkoxy/Hydroxy‐α‐methyltryptamines

Abstract

A simple method for the preparation of 7‐alkoxy/hydroxy‐α‐methyl‐DL‐tryptamines is reported. The key steps of the synthesis are the Japp–Klingemann coupling of 2‐piperidone‐3‐carboxylic acid 3 with diazonium salts 4, the Fischer‐type cyclization of hydrazones 5 to β‐carboline derivatives 6 and their hydrolysis to title compounds 8.     

Synthesis of an α‐Gal epitope α‐D‐Galp‐(1→3)‐β‐D‐Galp‐(1→4)‐β‐D‐Glcp NAc–lipid conjugate*

The synthesis of a neoglycoconjugate containing the Galili epitope trisaccharide connected to a spacer‐lipid entity is described. The α‐D‐Galp‐(1→3)‐β‐D‐Galp‐(1→4)‐β‐D‐GlcpNAc trisaccharide, equipped with a 3‐aminopropyl spacer, is efficiently assembled from easily accessible building blocks in a one‐pot procedure. Global deprotection of the trisaccharide and ensuing introduction of a bis(palmitamido)‐ propanamido moiety afforded title compound 1 as depicted in Scheme 1.     

Synthesis of Novel Anellated Pyranosides as Precursors of C‐Nucleoside Analogues Using Isopropyl 6‐O‐Acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose

Abstract

Isopropyl 6‐O‐acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose (3) was converted to the corresponding 3‐[bis(methylthio)methylene] derivative 4 with a push–pull activated C–C double bond. Treatment of 4 with hydrazine and methylhydrazine afforded the pyrano[3,4‐c]pyrazol‐5‐ylmethyl acetates 5a and 5b, respectively. Desulfurization of compound 4 with sodium boron hydride yielded the 3‐[(methylthio)methylene]hexopyranosid‐2‐ulose 7. Compound 7 was reacted with amines to furnish 3‐aminomethylene‐hexopyranosid‐2‐uloses 8, 9. Reaction of 7 with hydrazine hydrate, hydrazines, hydroxylamine, and benzamidine afforded the pyrazolo, isoxazalo, and pyrimido anellated pyranosides (10–13).     

Two Efficient Syntheses of Protected 4‐Deoxy‐D‐lyxo‐hexose (4‐Desoxy‐D‐mannose)

The formation of four differently protected 4‐deoxy‐D‐lyxo‐hexose derivatives 7, 8, 12, and 14 is described. In the first procedure, a nucleophilic displacement of the allylic mesylate 4 by hydride was combined with a highly stereoselective osmylation of olefin 6 to afford diol 7. In the second radical procedure, tributyl tin hydride was substituted by the cheap and environmentally friendly hypophosphorous acid as a hydrogen donor in the reduction of xanthate 13 to 4‐deoxy lyxo‐hexose 14.     

D,L‐α‐Tocopherol Synthesis Catalyzed by the Brønsted Acidic Ionic Liquids

Abstract

The synthesis of D,L‐α‐tocopherol from trimethylhydroquinone and isophytol using the Brønsted acidic SO₃H‐functionalized ionic liquids as catalysts was explored. The catalytic activities of the SO₃H‐functionalized ionic liquids were dependent on their anions. The yield of D,L‐α‐tocopherol also depended on the solvent, which was the reaction medium. A yield of 94.3% was obtained using the SO₃H‐functionalized ionic liquid with [BF₄ ^?] anion as catalyst in propylene carbonate/heptane. The reaction mixture exhibited good biphasic behaviors, so that the produced D,L‐α‐tocopherol could be separated by decantation. The SO₃H‐functionalized ionic liquids could be reused after the removal of water.