Synthesis of Four Orthogonally Protected Rare l-Hexose Thioglycosides from d-Mannose by C-5 and C-4 Epimerization

l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of the cheapest d-hexoses, d-mannose, using inexpensive and readily available chemicals, we developed a reaction pathway to obtain two orthogonally protected l-hexose thioglycoside derivatives, l-gulose and l-galactose, through the corresponding 5,6-unsaturated thioglycosides by C-5 epimerization. From these derivatives, the orthogonally protected thioglycosides of further two l-hexoses (l-allose and l-glucose) were synthesized by C-4 epimerization. The preparation of the key intermediates, the 5,6-unsaturated derivatives, was systematically studied using various protecting groups. By the method developed, we are able to produce highly functionalized l-gulose derivatives in 9 steps (total yields: 21–23%) and l-galactose derivatives in 12 steps (total yields: 6–8%) starting from d-mannose.     

Epimerization at C-2 of 2-substituted thiazolidine-4-carboxylic acids

2(R,S)-5,5-Trimethylthiazolidine-4-(S)-carboxylic acid ( 1a ), with a 3.3 to 1 predominance of the 2S (cis) isomer, was shown to epimerize at the C-2 position in neutral, protic solvents. This was manifested by mutarotation concomitant to changes in the ratios of the C-4 methine proton resonances in the nmr spectrum. Compound 1a was stable in dilute sodium carbonate solution, but underwent rapid equilibration in 1N hydrochloric acid. Acetylation of 1a gave an acetyl derivative ( 2a ) with exclusively 2S,4S stereochemistry. Chiral integrity at C-2 was proved by conversion of both 2a and its enantiomer 2b via their munchnone derivatives to enantiomeric dimethyl 1,1,3,5-tetramethyl-1H,2H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylates ( 4a and 4b ). Acetylation of 2-(R,S)-phenyl-5,5-dimethylthiazolidine-4(S)-carboxylic acid, afforded both the 2 S ,4S ( 6a ) and 2R,4S ( 6b ) epimers. Epimerization of 6a at C-4 gave the 2S,4R isomer ( 6c ) which was enantiomeric with 6b .     

C-2 Epimerization of N-Acetylglucosamine in an Oligosaccharide Derived From Heparan Sulfate

Abstract

The isolation of a heparan sulfate derived tetrasaccharide containing N-acetylmannosamine is described. The N-acetylmannosamine residue at the reducing terminus of heparin lyase derived tetrasaccharide is formed by base catalyzed C-2 epimerization of N-acetylglucosamine. This C-2 epimerization takes place under very mild conditions suggesting that this residue may be formed in small amounts under physiologic conditions.     

Reinvestigation to the C-7 Epimerization of Paclitaxel and Related Taxoids Under Basic Conditions

Base-promoted C-7 epimerizations of paclitaxel, 10-deacetylbaccatin III were investigated. It has been found that 13α-OH may play an important role in the equilibrium of C-7 epimers of paclitaxel and related taxoids.     

The First Synthesis of a Ribo-Hexos-5-Ulose: the L-Enantiomer

ABSTRACT

The title compound, previously unreported in either enantioform, and its 2,6-di-O-benzyl derivative have been synthesized through a stereocontrolled epimerization at C-2 of 6-O-protected methyl 3,4-O-isopropylidene-5-C-methoxy-β-D-galactopyranosides. The epimerization, performed through a high yielding sequence of oxidation-reduction owing to the cooperative role of the equatorial C-1 aglycon and the steric hindrance of the isopropylidene group, turned out to be completely diastereoselective. Whereas the unprotected L-ribo-hexos-5-ulose exists, as proved by NMR in D₂O, in five main tautomeric forms in a ratio of about 4:2:2:1:1, only two anomeric 1,4-furanosic forms are present at equilibrium in its 2,6-di-O-benzyl derivative, in ratios ranging from 10:1 to 7:3, depending on the prevalence of D₂O or CD₃CN in the solvent mixture.     

Preparation of O-1∼C-6 and O-7∼C-14 fragments of colletodiol

(5S,2E)-5-Tetrahydropyranyloxy-2-hexenoic acid and p-toluenesulfonylethyl (4R,5R,7R,2E)-7-hydroxy-4,5-dimethylmethylenedioxy-2-octenoate were prepared from ethyl acetoacetate and D-glucose, respectively.     

Mannuronolactone acetonide: easy access to C-3 OH and C-5 OH of mannose

The synthesis of d-mannuronolactone acetonide 1 is described from alginic acid and provides an efficient route for the manipulation at C-5 of mannose. Reduction gives a new acetonide of mannose, which, on further acetonation, gives [giving easy access to C-3 OH of mannose] together with a small amount of . Some silylated derivatives of mannuronolactone allow immediate access to the C-6 of mannose. Such intermediates are likely to be of value in the synthesis of derivatives of mannose.     

1H, 1 3C,and 1 5N Chemical shifts and 1H-1 5N and 1 3C-1 5N heteronuclear spin-spin coupling constants in the NMR spectra of 5-substituted furfural oximes

The ¹H, ¹³C, and ¹⁵N NMR spectra of ¹⁵N-enriched 5-substituted furfural oximes were investigated. It was shown that the chemical shifts of the ring atoms and the oxime group correlate satisfactorily with the F and R substituent constants, whereas their sensitivity to the effect of the substituents is lower than in monosubstituted furan derivatives. The constants of spin-spin coupling between the ring protons and the oxime group were determined. An analysis of the ¹H-¹H spin-spin coupling constants (SSCC) on the basis of their stereospecificity indicates that the E isomers have primarily an s-trans conformation in polar dimethyl sulfoxide, whereas the Z isomers, on the other hand, have an s-cis conformation. The signs of the direct and geminal ¹³C-¹⁵N SSCC were determined for 5-trimethylsilylfurfural oxime.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1172–1177, September, 1985.The authors thank N. O. Saldabol, L. M. Ignatovich, and N. P. Erchak for providing us with the investigated compounds.     

The Isomeric Composition of 6-Deoxy-D-XYLO-Hexos-5-Ulose in Aqueous Solution as Determined by 1H and 13C NMR

Abstract

Acid hydrolysis of 6-deoxy-1,2-O-isop ropylidene-α-d-xylo-hexo-furanos-5-ulose (4) yielded gummy 6-deoxy-d-xylo-hexos-5-ulose (1) as an isomeric mixture of two furanose forms, 6-deoxy-α-d-xylo-hexo-furanos-5-ulose and 6-deoxy-β-d-xylo-hexofuranos-5-ulose, and a pyranose structure 1R, 5R-6-deoxy-d-xylo-hexopyranos-5-ulose. The combined percentage (64%) of the furanoses represents an unusually large amount of free carbonyl form for a sugar when compared to simple hexoses and 2-hexuloses. Isomeric structures were determined in deuterium oxide solution by ¹H and ¹³C NMR.     

Preparation and comparative properties of antisera against glyco-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid linked to bovine serum albumin at the C-3, C-15 alpha, and C-24 positions

Anti glyco-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid antisera were prepared by immunizing rabbits with hapten-bovine serum albumin (BSA) conjugates coupled at the C-3, C-15 alpha, and C-24 positions on the bile acid molecule, and their properties were investigated by heterologous combination assay using 125I-labeled tracer. The antiserum raised against the C-3 BSA conjugate showed poor titer and specificity, while the antisera from the other two conjugates showed satisfactorily high affinity constants (Ka = 5.0 x 10(8) and 7.0 x 10(8) M-1) and reasonable specificity, exhibiting negligible cross-reactivities with other major human bile acids and cholesterol. Among the unsaturated bile acids tested, high reactivity was observed with tauro-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid, which suggested that bridge phenomena were significant in this assay system.     

Preparation of CaZrO3 Powder Through Oxalate Precipitation Route

ＰｒｅｐａｒａｔｉｏｎｏｆＣａＺｒＯ＿３ＰｏｗｄｅｒＴｈｒｏｕｇｈＯｘａｌａｔｅＰｒｅｃｉｐｉｔａｔｉｏｎＲｏｕｔｅＺＨＥＮＧＷｅｎ－ｊｕｎ;ＬＩＵＣｈｕａｎａｎｄＰＡＮＧＷｅｎ－ｑｉｎ（ＫｅｙＬａｂｏｒａｔｏｒｙｏｆＩｎｏｒｇａｎｉｃＨｙｄｒｏｔｈ...     

Synthesis of Sialic Acid Analogues with the Oxime Group at C-4 Or C-5 of KDN 1

Abstract

The readily available methyl (methyl 3-deoxy-5,8:7,9-di-O-isopropylidene-β-D-glycero-D-galacto-2-nonulopyranosid)onate (7) was converted in five synthetic steps into methyl (methyl 4-acetamido-3,4-dideoxy-β-D-glycero-D-talo-2-nonulopyranosid)onate (11). Selective protection of the C-4, C-7, C-8 and C-9 hydroxy groups of methyl (methyl 3-deoxy-8,9-O-isopropylidene-β-D-glycero-D-galacto-2-nonulpyranosid)onate (2) followed by oxidation of the C-5 hydroxy group and then its oximination gave 5-hydroxyimino derivatives (15 and 16).

     

Palladium-catalyzed enantioselective C-3 allylation of 3-substituted-1H-indoles using trialkylboranes

We have developed a new enantioselective C-3 allylation of 3-substituted indoles using allyl alcohol and trialkylboranes. Asymmetric syntheses of 3,3-disubstituted indolines and indolenines in enantiomeric excesses up to 90% have been achieved using the bulky borane 9-BBN-C6H13 as the promoter of the reaction. The dependence of the selectivity on the nature of the borane suggests that the boron reagent has a role beyond promoting ionization of the allyl alcohol. A protocol for oxidation of indolenines to oxindoles has also been developed and led to a formal synthesis of (-)-phenserine.     

Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation

Pyridines are ubiquitous aromatic rings used in organic chemistry and are crucial elements of the drug discovery process. Herein we describe a new catalytic method that directly introduces a methyl group onto the aromatic ring; this new reaction is related to hydrogen borrowing, and is notable for its use of the feedstock chemicals methanol and formaldehyde as the key reagents. Conceptually, the C-3/5 methylation of pyridines was accomplished by exploiting the interface between aromatic and non-aromatic compounds, and this allows an oscillating reactivity pattern to emerge whereby normally electrophilic aromatic compounds become nucleophilic in the reaction after activation by reduction. Thus, a set of C-4 functionalised pyridines can be mono or doubly methylated at the C-3/5 positions.

Electron poor pyridines can be activated by reduction and then methylated at C3/5 using formaldehyde.     

Dimerization by Hetero Diels-Alder Reaction of Methyl 4,6-O-Benzylidene-3-Deoxy-3-C-Methylene-α-D-Erythro-Hexopyranosid-2-Ulose

Abstract

The dimerization by hetero Diels-Alder reaction of methyl 4,6-O-benzylidene-3-deoxy-3-C-methylene-α-D-erythro-hexopyranosid-2-ulose was found to be regio and stereospecific. The structure of the cycloadduct was assigned from NMR spectrographic and X-ray crystallographic results. These results indicated that this cycloaddition occurred by a concerted hetero Diels-Alder reaction with inverse electron demand.     

Preparation of 3(5)-phenyl-1-hydroxypyrazole 2-oxide and 4-methyl-3(5)-phenyl-1-hydroxypyrazole 2-oxide

Nitrosation of acrylophenone oxime or of methacrylophenone oxime with n-butyl nitrite in the presence of pyridine and copper(II) sulfate gives the copper complexes of the title compounds. The free 1-hydroxypyrazole 2 -oxides are isolated by treating the copper complexes with dilute sodium hydroxide, filtration, and acidification of the basic filtrates. The title compounds are the first examples of 1-hydroxypyrazole 2 -oxides in which the C3(5) ring position is unsubstituted.