Aleksander Zamojski

Synthesis of methyl 2,3-dideoxy-DL-alk-2-enopyranosides from furan compounds : A general approach to the total synthesis of monosaccharides

Abstract A method of converting furan derivatives via 2,3-dideoxy- DL -alk-2-enopyranos-4-uloses, a new class of sugar compounds, into methyl 2,3-dideoxy- DL -alk-2-enopyranosides is described. Furfuryl alcohol, 2(1,2-O-isopropylidene-1,2-dihydroxyethyl)furan, 1(2-furyl)ethanol and 2(2-furyl)glycerol 1,3-diacetate treated with bromine in methanol gave corresponding 2,5-dimethoxy-2,5-dihydrofuran derivatives, which hydrolyzed with diluted sulphuric acid afforded 2,3-dideoxy- DL -pent-2-enopyranos-4-ulose, 2,3-dideoxy- DL -hex-2-enopyranos-4-ulose, 2,3,6-trideoxy- DL -hex-2-enopyranos-4-ulose and 6-O-acetyl-5C-acetoxymethyl-2,3-dideoxy- DL -hex-2-enopyranos-4-ulose, respectively. The latter treated with methyl orthoformate in the presence of Lewis acids yielded corresponding methyl glycosides, which were reduced with sodium borohydride to give appropriate pairs of stereoisomeric methyl 2,3-dideoxy- DL -alk-2-enopyranosides. All stereoisomers were separated and their configuration was established by PMR spectra. 1-O-Acetyl derivatives of 2,3-dideoxy- DL -alk-2-enopyranos-4-uloses were obtained.

Synthesis of alkyl 4,6-di-o-acetyl-2,3-dideoxy-α-d-threo-hex-2- enopyranosides from 3,4,6-tri-o-acetyl-1,5-anhydro-2-deoxy- d-lyxo-hex-1-enitol (3,4,6-tri-o-acetyl-d-galactal)

Abstract 3,4,6-Tri- O -acetyl- d -galactal, on treatment in 1,2-dichloroethane with alcohols and stannic chloride as catalyst, readily undergoes allylic rearrangement-substitution, forming alkyl 4,6-di- O -acetyl-2,3-dideoxy-α- d - threo -hex-2-enopyranosides in yields of 43-92%. Alkyl 3,4,6-tri- O -acetyl-2-deoxy-αβ- d - lyxo -hexopyranosides are formed as side-products in yields of 2-14 %. Stannic chloride-catalysis is also useful in allylic rearrangement of 3,4,6-tri- O -acetyl-1,5-anhydro-2-deoxy- d - arabino - hex-l-enitol (3,4,6-tri- O -acetyl- d -glucal) which, with methanol or ethanol, affords the corresponding alkyl 4,6-di- O -acetyl-2,3-dideoxy-α- d - erythro -hex-2-enopyranosides in yields of 83 and 94%.

The Synthesis of Sugars from Non-Carbohydrate Substrates

Publisher Summary This chapter describes the syntheses of sugar-type compounds containing four or more carbon atoms, an aldehyde or a ketone group, and a minimum of two hydroxyl groups (or their equivalents, such as amino or thiol groups) with at least one of them being bound to a center of chirality. Among the variety of noncarbohydrate precursors, acetylenes and alkenes have found wide application as substrates for the synthesis of monosaccharides. The parent compounds of all pyranoses—the 2H - and 4H -pyrans—and their derivatives are impractical as substrates for the synthesis of sugars. The formation of furan derivatives in acid-catalyzed dehydrations of carbohydrate substrates is a well known reaction. 1,2-Ethenediyl carbonate (1,3-dioxol-2-one; vinylene carbonate) is a readily available, versatile synthon having pronounced dienophilic properties. For the synthesis of optically active sugars, a number of natural compounds have been successfully employed. The syntheses of sugars described in this chapter demonstrate the general utility of starting materials employed as the precursors of various sugars of desired structure.

New syntheses of d- and l-glycero-d-manno-heptoses

Abstract Three methods for the synthesis of the title compounds starting from benzyl 2,3,4-tri-O-benzyl-α- d -manno-hexodialdo-1,5-pyranoside (7 have been elaborated. Conversion of 7 into the cyanohydrin followed by reduction to give the amine and then deamination gave a derivative of l -glycero- d -manno-heptose in low yield. Condensation of 7 with 2-methylfuran gave two stereoisomeric 6-C-(2-methyl-5-furyl) derivatives. The preponderant stereoisomer was ozonised and then reduced to give a derivative of d -glycero- d -manno-heptose. Condensation of 7 with allyloxymethylmagnesium chloride gave derivatives of both heptoses in good yield and with an l -glycero d -glycero ratio of 3.2:1. Deprotection of these derivatives gave the heptoses in high yield.

The acid-catalysed reaction of thiols with alkyl 2,3-dideoxy-glyc-2-enopyranosides or glycals

Abstract The acid-catalysed (HCl or SnCl 4 ) reaction of alkyl 2,3 dideoxy-glyc-2-enopyranosides or 3,4,6-tri-O-acetyl- D -glycals with thiols leads to mixtures of alkyl 2,3-dideoxy-1-thio-glyc-2-enopyranosides and 3-S-alkyl-3-thioglycals. Under equilibrium conditions the latter are the preponderant products of the reaction. Cross experiments have confirmed the intermediacy of the allylic carbocation in the reaction. A rationalization of the substitution reactions of 1,2- and 2,3-unsaturated sugars based on HSAB principle has been proposed.

Reaction of sugar thiocyanates with Grignard reagents. New synthesis of thioglycosides.

Abstract Glycosyl thiocyanates having hydroxyl groups protected with acetyl or benzoyl groups react readily at −40°C with Grignard reagents to afford the corresponding alkyl or aryl thioglycosides in good yields. Monosaccharide derivatives having the SCN grouping at other positions form under similar conditions thioethers. Axial thiocyanates do not react. Elevated temperatures induce side reactions leading to mercaptans.

Naphto- and anthraquinones of Streptomyces thermoviolaceusWR-141. Structures and model syntheses

Abstract In addition to previously identified antibiotic granaticin 1 Streptomyces thermoviotaceus WR-141 was shown to produce dihydrogranaticin 2, and anthraquinone pigments 5, and 6. Model synthesis of the chromophore and dihydropyran part of these antibiotic pigments are described.

Structural analysis of the heptose/hexose region of the lipopolysaccharide from escherichia coli K-12 strain W3100

The disaccharide L-glycero-D-manno-heptosyl-D-glucose was isolated from the lipopolysaccharide (LPS) of Escherichia coli K-12 strain W3100 after partial hydrolysis with acid, and the structure was determined by methylation analysis, n.m.r. spectroscopy, and comparison with a synthetic standard. In addition, the oligosaccharides L,D-Hep-D-Glc-D-Glc and L,D-Hep-D-Glc-D-Glc-D-Glc were isolated, and their structures were established by g.l.c.-m.s. and methylation analysis. The results indicated that L-glycero-D-manno-heptose, a characteristic constituent of the inner core region, may also occur in the outer core region which, in E. coli, is generally composed of hexoses. A revised structure of the carbohydrate backbone of the hexose/heptose region of the LPS is given.

Asymmetric photocycloaddition between furan and chiral alkyl glyoxylates

Abstract High-pressure mercury lamp irradiation of chiral alkyl glyoxylates [ R (−)-menthyl, R (−)- and S (+)-2-octyl, R (−)-and S (+)-2, 2-dimethyl-3-butyl] with furan led to alkyl 2,7-dioxabicyclo-[3.2.0] hept-3-ene-6-car☐ylates ( 13a–e ) exhibiting low (2.5–7.3%) optical purity. Compounds 13a–e were isomerized to alkyl 3-furylglycolates ( 14a–e ) in good yield. Configuration S was assigned to levorotary methyl 3-furlymethoxyacetate. Two interpretations of the results of asymmetric synthesis were proposed.

Asymmetric photocycloaddition between furan and optically active ketones

Abstract The photochemical reaction between 3β-acetoxyandrost-5-en-17-one 4 or (–)-methone 5 and furan was preceded by isomerization of the ketones to the corresponding γδ-unsaturated aldehydes which subsequently added to furan furnishing 6-substituted 2,7-dioxabicyclo-[3.2.0]hept-3-enes, 8 and 9 . Under the same conditions 1,2:5,6-di- O -isopropylidene α- d -ribo-hexofuranos-3-ulose 12 reacted with furan without any isomerization and afforded all four stereoisomeric bicyclic photoadducts 14–17 . The ratio of the products resulting from the approach of the furan molecule to 12 from the less hindered and from the more hindered sides was 3:1. This pointed at the decisive role of steric factors in controlling the course of photochemical cycloaddition.