Maillard Reaction: Investigation of the Chemical Structure of Melanoioins Synthesized from D-Xylose and Glycine Using 13C and 15N Specifically Labeled Reactants

Abstract

Melanoldins were Isolated 1n 36% yield w/w from molar solution of D-xylose and glydne-2-¹³C (A); D-xylose and glycine-l-¹³C (B); D-xylose-1-¹³C and glydne (C); D-xylose and glyclne (D); D-xylose and glycine-¹⁵N (E). Each solutTon was kept at 68[ddot]C until complete disappearance of xylose as evidenced by NMR. ¹³C and ¹⁵N solid state nuclear magnetic resonance and diffuse reflectance Infrared spectrometry were used in their structural elucidation before and after basic and add hydrolysis. Both C-1 and C-2 of glycine were Incorporated Into the polymers. In the ¹³C CP-MAS NMR spectra, C-1 gave a single peak in the polymer at 171.3 ppm, while C-2 gave three at 48.1, 31.2 and 22.5 ppm. Area measurements of the respective peaks Indicated that 50% of the Incorporated glycine had undergone decarboxylatlon. C-1 of xylose was Incorporated into the polymers mainly as two types of carbons at 68.8 ppm (CHOH, C-OH) and at 133.3 ppm (unsaturated C). Hydrolysis (6N HC1) led to a 20% reduction 1n weight of the melanoldlns, a decrease of 2% in C and 10% in N. ¹³C CP-MAS NMR revealed after hydrolysis of D, the disappearance of signals at 69, 110, 152, 172 and 200 ppm. Hydrolysis of A and B reduced all signals originating from C-1 and C-2 of glydne, while hydrolysis of C reduced only the signal of 68.8 ppm. ¹⁵N CP-MAS NMR of hydrolyzed E showed a greatly reduced amide resonance at 100 ppm, with more pyrrole or imino N. DR-IR showed a reduction 1n both the 1625 and 1550 cm^-1 bands with a concurrent appearance of a 1715 cm^-1 band.     

A Novel Oxazolidine Derivative from Xylose and Urea

Abstract

Reaction of equiraolecular amounts of xylose and urea in D₂O at 68 °C, monitored by ¹³C NMR, gave a six carbon xylofuranosyl derivative as the major product. No intermediate in the formation of this monomeric compound was detected. The xylofuranosyl derivative was subsequently isolated and purified from a six week 0.1 molar reaction of xylose and urea in H₂O. Its structure, α-d-xylo-furano[1,2-d]oxazolidin-2-one 1, was confirmed by elemental analysis, ¹H coupled and decoupled ¹³C NMR, ¹H NMR, IR and DCI-MS. The ¹H NMR and GC-MS (El, DCI) of the N-acetyl-di-O-acetyl derivative 2 were in agreement with structure 1.     

Synthesis of 2-Carbamoyl-2-Deoxy Glycosides

Abstract

Recently we have reported the addition of trichloracetyl isocuyanate to glycals 1 _1,2,3. The reaction led to the highly stereoselective formation of a mixture of unstable [2+2] and [4+2] cycloadducts 2 and 3. The isocyanate adds to the glycal moiety anti to the substituent at C-3. The addition of benzylamine to the reac6tion mixture led to N-deprotection of 2 and allowed us to isolate stable bicyclic β-lactams 4 _1-3. We have shown also that 2 (a mixture of α-L-gluco and β-L-manno isomers) obtained from L-rhamnal 1 (R¹[dbnd]Ac, R²[dbnd]CH₃ under high pressure, when treated with methanol, underwent a rapid trans opening of the four-membered ring to give respective glycosides 5(β-L-gluco and α-L-manno isomers). On the other hand 3 (R¹[dbnd]Ac, R²[dbnd]CH₃) under the same conditions added a molecule of methanol to the C[dbnd]N double bond affording 6.     

The Formation of Phosphacycloheptatrienes in Ring Enlargement Reaction

Abstract

The forrmation of substituted phosphacycloheptatrienes in ring expansion reaction(s) is describzd. From thc: reac-tion of 3,4-dimethyl-l-phenyl-3-phospholene-l-oxide(1,R¹ = c₆H₅, R₂=R₃ = CH₃) with dichlorocarbene under liquid-liquid phase transfer circumstances not the expected adduct but the appropriate phoshacycloheptatrisne (4, R_l, R₂,R₃ as above) was prepared. The formation of this product can be explained assuming two ring expansions effected by two series of dichlorocarbene addition and cyclopropane ring opening. In the similar reaction of the methoxy-phospholenc derivative (1, R¹=CH₃O, R² = R³ = CH3 four other products are also formed beside the phosphacyclohcptatriene. Again phosphacycloheptatrienes (4) are formed as the result of dichlorocarbene addition to the regioisoners of dihidrophosphorins (2) obtained from the phospholene-dichlorocarbene adducts by thermolysis. The same product can be derived from each regioisomeric pair.     

The Reaction of Diethanolamine with 2-Chloronitrobenzene-A Reinvestigation

In a report on the reaction of 2-chloronitrobenzene (1) with diethanolamine (2), Meltsner et al ¹ claim that the expected S_NAr product, N-(2-nitrophenyl)diethanolamine (3), is not formed; rather that the products are 2,2′-dichloroazobenzene (4), 2-nitrophenol (5), 2-chloroaniline (6) and 4-(2-aminophenyl)morpholine (7). Similar products in which the nitro function is reduced are also reported² for the corresponding reaction with ethanolamine. In this laboratory, in an attempted preparation of 2,2′-dichloroazobenzene (4) for reference purposes in photochemical studies on the antineoplastic agent 5-(3-azido-4-chlorophenyl)-6-ethyl-pyrimidin-2,4-diamine³, the expected S_NAr product (3) was obtained along with other products.     

A Conventient Synthesis of 3-Hydroxy-4-chromanone Using Iodobenzene Diacetate

A useful synthesis of 3-hydroxy-4-chromanone (6) is not currently available. Lead tetraacetate oxidation of 4-chromanone (4) yields the C(3) acetoxy derivative but this compound could not be deacetylated to 6.¹ Recently Donnelly and Maloney reported² that the Algar-Flynn-Oyamada reaction (H₂O₂/CH₃OH/NaOH), which is commonly used for the conversion of o-hydroxychalcones (1) into 3-hydroxyflavanone (2) and 3-hydroxyflavones (3), does not yield 6 when applied to o-hydroxya-crylophenone 1 (R = H). The authors found that under less basic conditions using K₂CO₃ some 6 is formed but the major product is catechol. These observations clearly indicate the necessity of developing a method for making 6. The present note describes a staightforward way of preparing 3-hydroxy-4-chromanone (6) in good yield.     

Reaktionen Mit Trimethylsilylhalogeniden an Derivaten Der Digitoxose

Abstract

Treatment of methyl 3,4-di-O-acyl-2,6-dideoxy-α-D-ribo-hexo-pyranoside 1 or 2 with trimethylsilyl halide leads to the formation of a complex mixture of α-D-ribo-hexopyranosyl halides 3 or 5 together with the educts 1 or 2 as well as their β-anomers 8 or 9. The bromides 3 and 5, suitable for glycosidations, are preferably obtained by reaction of the digitoxose acetate derivatives 6 and 7, respectively, which in turn are prepared from 1 and 2 by mild acetolysis. Further reaction of the halides 3 to 5 with trimethylsilyl halides gives rise to a quantitative formation of the 2,3,6-trideoxy-4-0-acyl-3-halo-α-D -arabino-hexopyranosyl halides 10 to 12. In another reaction sequence starting with the olivose triacetate 20 the formation of 10 via the halide 13 is demonstrated. Structural evidence for the halides 10 to 12 is given by ¹H NMR data as well as by analyses of their glycosides 14 to 19. The results support a mechanistic interpretation for the formation of 10 to 12 via a 3,4-acetoxonium ion as the key intermediate obtained from 3 by an S_Nfi and from 13 and S_N2i step. Final conversion into the terminal halodeoxy compounds 10 to 12 proceeds by and S_N2 reaction with the halide ion.     

N-(Chlorosulfinyl)-Imidazole as a New Imidazole Transfer Reagent1

The usefulness of diimidazoles² such as N, N′-carbonyldi-imidazole (1), and N, N′-thionyldiimidazole (2) in organic synthesis has been accumulated recently. In connection with the continuing our studies on the reaction using 1 or 2 ³ (carbonyl, thionyl, and imidazole transfer reactions), our particular interest was focused on the synthesis of N-(chlorosulfinyl)-imidazole (3) in which one imidazole group in 2 was replaced by the other leaving group (Cl). Also, 3 was interesting for preparative purposes as a chlorine atom could be introduced via the addition reaction of 3 to carbonyl compounds as known in the reaction of 1 or 2 with ketones.     

Isothiocyanatochloromethylphosphonates and Phosphinates – Versatile Synthones for Obtaining of S (Se), N,P–Containing Heterocycles

Abstract

Isothiocyanatochloromethyl(thio)phosphonates and (thio)-phosphinates 1 (X=O, S; R¹ = OPh, CH₂Cl, NCS; R² = H, Cl have been found to be convenient starting material for synthesis of a variety of S (Se), N, P-containing cyclic compounds. They react with different proton containing nucleophiles in the presence of a base with formation of saturated 2 and unsaturated 3 five membered phosphacyclanes. Diisothiocyanatodichloromethylphosphonates 1 (R¹ = NCS, R² =Cl) produce with amines and thiols appropriate bicyclic compounds 4.     

Stereoselective Synthesis of 3-C-Branched-Chain Sugars by Aldol Reaction of Furanos-3-Uloses with Acetone

Abstract

Aldol reaction of 1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-erythro-pentofuranos-3-ulose (1) with acetone in the presence of aqueous K₂CO₃ afforded 3-C-acetonyl-1,2-O-isopropylidene-5-O-tertbutyl-dimethylsilyl-α-D-ribofuranose(2). Similar reaction of 1,2:5, 6-di-o-isopropylidene- α-D-ribo-hexofuranos-3-ulose (3) afforded 3-C-acetonyl-1,2:5, 6-di-o-isopropylidene- α-D-allofuranose (4) and (1R, 3R, 7R, 8S, 10R)-perhydro-8-hydroxy-5,5,10-trimethyl-2,4,6,11,14-pentaoxatetracyclo[8,3,1,0^1,8,0^3,7] tetradecane. The stereochemistry of the new chiral centers were determined by ¹H NOE experiments.     

Synthesis of 2′,3′-Dideoxy-2′-Fluorokanamycin A

2′,3′-Dideoxy-2′-fluorokanamycin A (23) was prepared by condensation of 6-azido-4-0-benzoyl-2,3,6-trideoxy-2-fluoro-α-D-ribo-hexopyranosyl bromide (13) and a protected disaccharide (19). Methyl 4,6-0-benzylidene-3-deoxy-β-D-arabino-hexopyranoside (5) prepared from methyl 4,6-0-benzylidene-3-chloro-3-deoxy-β-D-allo-hexopyranoside (1) by oxidation with pyridinium chlorochromate followed by reduction with Na₂ S₂O₄ was fluorinated with the DAST reagent to give methyl 4,6-O-benzylidene-2,3-dideoxy-2-fluoro-β-D-ribo-hexopyranoside (7). Successive treatment of 7 with NBS, NaN₃ and SOBr₂ gave 13. The structure of the final product (23) was determined by the ¹H and ¹⁹F and shift-correlated 2D NMR spectra.     

REACTIONS OF DITHIOLETHIONES WITH N,N-DICHLOROAMIDES

Abstract

Dependent on the starting materials and the reaction conditions N,N-dichloroamides Cl₂N-X (X = COaryl, CO₂alkyl, SO₂aryl, SO₂N(alkyl)₂) react with dithiolethiones 1 and 5 to N-(dithiolyliden)amides 2, 6, S-(dithiolylidene)sulfimides 3, thionoxides 7 and dithiolones 4, 8. The mechanisms have been studied.     

On the Stereoselectivity of Fluorine and Acetylhypofluorite Additions to Glycals: The Synthesis of 2-Deoxy-2-Fldorohexoses

Electrophilic syn additions of fluorine and acetylhypofluorite across double bonds in 3,4,6-tri-0-acetyl-D-glucal (1a) and D-glucal (1b) followed by acid hydrolysis gave mixtures of 2-deoxy-2-fluoro-D-glucose (8) and 2-deoxy-2-fluoro-D-mannose (9). These addition reactions were conducted in various solvents with a view to investigating the reaction mechanism based on the product distribution analysis by ¹⁹F NMR. Tight ion pair intermediates (4 and 5) have been invoked to explain the stereospecific characteristics of the addition of fluorine or acetylhypofluorite to glycals. The relative stabilities of these intermediates control the product distributions and are governed by a) the anomeric effect (axial vs equatorial preference of C(1) electronegative substituents in pyranose rings), b) dipole-dipole interactions of the lone pairs of electrons on the ring oxygen and the electronegative substituents on C(2), and c) the gauche relationship that exists between the C(2) fluorine and polar groups in the molecule. The overall contribution of these three factors largely depends upon the polarity of the solvent. A rationale for the ¹⁹F NMR chemical shifts as well as the anomeric distributions of the α and β anomers of 2-FDG (8) and 2-FDM (9) has been proposed.     

New Preparation of Cyclic Acyloxyphosphorane by Reaction of Glyoxylic Acid with Phosphorus(III) Compounds

We have recently found that the reaction of α-keto acids (1) with phosphorus (III) compounds (3) yielded cyclic acyloxyphosphoranes(C-AOPs, 4), a new class of pentacovalent phosphorus species having a P-OC(O) group.^{1, 2)} The present paper deals with a new reaction of glyoxylic acid (2) with 3 to give C-AOPs (5) having no substituent at the C-3 position. 1 is an α-keto acid whereas 2 can be taken as an α-formyl acid. Although it is well known in the field of organic chemistry that the formyl group often behaves differently from a keto group, the reaction of 2 with 3 provides an example in which both groups behave in a similar manner.     

Synthesis of O-α-L-Fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D-glucopyranose. The H-Blood Group Specific Trisaccharide

Abstract

Different reaction conditions were investigated for the preparation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (5). Compound 5 on reaction with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide afforded the 4-O-substituted 2-acetamido-2-deoxy-β-D-glucopyranosyl derivative which, on O-deacetylation, gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-glucopyranoside (8). The trimethylsilyl (Me₃Si) derivative of 8, on treatment with pyridineacetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having an O-acetyl group selectively introduced at the primary position and Me₃Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol to afford benzyl 2-acetamido-4-O-(6-O-acetyl-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside, which on isopropylidenation gave the desired, key intermediate benzyl 2-acetamido-4-O-(6-O-acetyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (12). Reaction of 12 with 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide under catalysis by bromide ion afforded the trisaccharlde derivative from which the title trisaccharide was obtained by systematic removal of the protective groups. The structures of the final trisaccharide and of various intermediates were established by ¹H and ¹³C NMR spectroscopy.     

Selective α-D-Galactosylation of Benzyl 4,6-O-Benzyhdene-β-D-Galacto-Pyranoside with 2,3,4,6-Tetra-O-Benzyl-α-D-Galactopyranosyl Bromide Under Catalysis by Halide Ion

Abstract

Selective glycosylation of benzyl 4,6-O-benzylidene-β-D-galacto-pyranoside (1) with 1.5 mole equivalent of 2,3,4,6-tetra-O-binzyl-α-D-galactopyranosyl bromide (2) catalyzed by halide ion gave the (1→2)-α-(5) and (l→3)-α-D-linked disaccharide (7) derivatives in 22 and 40% yields, respectively. The D-galactose unit at the reducing end of 2-O-α-D-galactopyranosyl-D-galactose [11) at equilibrium in D₂O was shown By ¹³C NMR spectroscopy to exist in the pyranose and furanose forms in the ratio of ～2:1.     

Methylation of Dimedone

In connection with our synthetic approach to pentacyclic triterpenes,¹ we have required substantial amounts of 2,5,5-trimethyl-1,3-cyclohexanedione (methyldimedone, 2), which is available by methylation of dimedone (1).² However, methylation may also afford the 2,2-dimethyl product 3, the methyl ether 4, and the C, O-dimethyl product 5.     

Synthesis of 2-Aryl-1H-s-Triazolo[1, 5-a] Benzimidazoles

2-Aroylaminobenzimidazoles (2) have been converted into 1(2-benzimidazolyl)-5-aryl-1H-tetrazoles (4) by treatment with PCl₅ followed by azidation with NaN₃ in aqueous acetone solution. Pyrolysis of 4 in diphenylether yielded 2-aryl-1H-s-triazolo [1,5-a] benzimidazoles (6). The product of benzylation of 6a has been characterised. A reasonable pathway for the formation of 6 from 4 has been suggested.     

Oxygenation of Trimethylsilylallenes Readily Obtainable from Organoboranes. Syntheses of 1-Trimethylsilyl-1-alkyn-3-ones and 1-Trimethylsilyl-1-alkyn-3-ols

Abstract

Recently we have reported that the reaction of sodium methoxide with ate-complexes (1) readily prepared from trimethyl-silylpropargyl phenyl ether and organoboranes gives trimethyl-silylallenes (2) selectively (eq. 1).¹ In an attempt to find a new synthetic application of such silylallenes (2), the oxidation of 2 was examined. Although the usual oxidants such as m-chloro-perbenzoic acid were found to be unsuitable for the oxidation of the silylallenes, it was discovered that 2 was autoxidized at room temperature to propargylic hydroperoxide (3) (eq. 2). For example, the acidified starch-iodine test² strongly suggested the presence of the organic hydroperoxide in the reaction mixture obtained from 1,2-heptadienyltrimethylsilane (2, R=Bu) and oxygen. The hydroperoxide (3, R=Bu) was isolated in a 40% yield by distillation, 45–48 [ddot]C/0.1 mmHg. In the infrared spectrum, the OH stretching frequency appears at 3430 cm^?1 and the C°C at 2180 cm,^?1