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.     

An Efficient,General Synthesis of Alkylsulfinyltoluidides

Corey and Durst¹ have demonstrated the utility of N,α-dilithioalkyl-sulfinamides (1) as reagents for the quasi-Wittig reaction with aldehydes and ketones, and a one-step preparation of ketones from esters. Despite this promise, these reagents have seen few applications, due in large part to the inconvenience of preparing the precursor sulfinamide (2) via the corresponding sulfinyl chloride.^1,2     

New and Stereospecific Synthesis of α-Ethylenic Ketones

Abstract

H. Kise et al¹ have shown that the reaction of β-propiolactones 1 with ylides 2 give phosphonium carboxylate betaïne 3. We now report that, carried out under different conditions, reaction of lactones 1 with the same ylides proceeds through pathway (b). Thermolysis of 4 affords α-ethylenic ketones 5. The mecanism of this new extrusion reaction of triphenylphosphine oxyde probably involves the generation of an oxaphosphene as an intermediate.     

Hypochlorous Acid. A Synthesis of α-Chloro-β-Lactones

Herein we report that the reaction of hypochlorous acid with certain α,β-unsaturated acids in a two phase system^1,2 affords α-chloro-β-lactones^3,4 in poor to fair yield. Thus, β-lactones 4, 5, and 6 are obtained from acids 1, 2 and 3, respectively, where the β-carbon of the acid is disubstituted.     

Azlactone Synthesis. 2-Phenyl-2-Oxazolin-5-One

Abstract

2-Phenyl-2-oxazolin-5-one (3) has been used as an intermediate in the synthesis of α-amino acids¹, derivatives of α-amino acids,² and peptides.³ Procedures for the dehydration/cyclization of hippuric acid (1) leading to the isolation of azlactone 3, have been reported using acetic anhydride,⁴ phosphorus trihalides⁵, and N, N′-dicyclohexylcarbodiimide.⁶ We report herein an alternative, high yield procedure utilizing a water soluble carbodiimide.     

A Convenient Synthesis of 5-Bromo-2-Pentanone

During a series of studies aimed at the total synthesis of pentacyclic triterpenes¹ we have examined the reaction of enollactones of type 1 with a variety of Grignard reagents. ^1c,2 In one of our problems we required the organometallic reagent 2a derived from the title compound 2b. A previous literature report for the preparation of this compound involved the reaction of α-acetylbutyrolactone 3 with aqueous HBr followed by steam distillation.³ In our hands the yields of 2b via this route were non-reproducible and at best, less than 15%.     

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.     

First Stereqselective Synthesis of Nitrophenyl 2-Deoxy- β-D-glycosides

α-Dithiophosphates of peracetylated 2-deoxyhexc-pyranoses, 1a, 1b and 2, uhich are easily prepared by addition of organic phosphorodithioic acids to glycais react smoothly with resin-bound 2- and 4-nitrophenoxides to give stereoselectively the respective nitrophenyl 2-deoxy-β-D-hexopyranosides (3, 4, 5 and 6) in high yields. Glycosylation of the 2, 4-dinitro'phenoxide, however, leads with comparable stereoselectivity to 2,4-dinitrophenyl 2-deoxy- α-D-hexopyranosides (7 and 8).

Glycosides 3 - 6 are quantitatively deacetylatec by Amberlyst A-26 (OH^-), whereas glycosides 7 and 8, under the same reaction conditions undergo splitting of the O-glycosidic bond.     

Synthesis of Heterobicycles of δ-Lactam Fused with 1,3-Diazaheterocycles by the Reaction of Heterocyclic Ketene Aminals with α,β-Unsaturated Carboxylic Esters

Heterobicycles of δ-lactam fused with imidazolidine (4, 7), hexahydropyrimidine (5, 8), or hexahydro-1, 3-diazepine (6, 9) were synthesized by the reaction of heterocyclic ketene aminals 1, 2 or 3 with ester of α,β-unsaturated carboxylic acids.     

Synthesis of C-Sulfonylcarbohydroximoyl Chlorides from α-Diazosulfones and Nitrosyl Chloride1

Previous investigations in this laboratory have been concerned with reactions of α-diazosulfones² (1) with electrophilic reagents, such as sulfenyl chlorides², t-butyl hypochlorite^2,3 and halogens⁴, which lead to threefold electronegatively substituted methanes (2). As was anticipated, α-diazosulfones closely resemble α-diazoketones in these reactions.⁵     

Synthesis of Acylacetylenes from α-Diazo-β-Hydroxylcarbonyl Compounds

A facile synthesis of α-diazo-β-hydroxy ketones and esters by the condensation of aldehydes or ketones with acyldiazomethanes was reported recently.² Exposure of the trifunctional compounds to boron trifluoride in ether-acetonitrile solution leads to acylacetylenes. Thus substances 1 and 3 were converted readily into acetylenes 2 and 4 respectively.³ This makes available a simple two-step procedure for the synthesis of conjugated acetylenic carbonyl compounds.     

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.     

1,1-DIANIONS OF ALKYL PHENYL SULPHONES AS SYNTHETIC INTERMEDIATES IN CYCLIZATION REACTIONS

Abstract

α-Sulphonyl carbanions are known to be good nucleophiles both in intermolecular and in intramolecular reactions¹. In the same way gem-dimetalloderivatives of alkyl phenyl sulphones I a,b readily add to aldehydes and ketones to give the (β-hydroxy compounds II in the case of dilithioderivatives Ia, while from dimagnesioderivatives Ib α, β-unsaturated sulphones III are also obtained².     

Asymmetric Synthesis of Aryl 2-Piperidyl Methanols from a Chiral α-Aminonitrile Precursor

Synthesis of enantiomerically pure phenyl 2-piperidyl methanols from a convenient chiral α-aminonitrile 1 is described. Reaction with aldehydes of the anion generated from 1 leads to threo (αR, 2R) products, whereas treatment of 1 with organolithium reagents affords erythro (αR, 2S) compounds.     

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.     

Darstellung Von β-D-Olivosyl(1→3)-D-olivosiden Aus Mithramycin

Abstract

The benzyl glycoside 4 obtained from 2-bromo-2-deoxy-α-0-quinovosyl bromide 1, readily accessible by the dibromomethyl methyl ether reaction of 2, is deformylated to give the monohydroxy compound 5 which is used in glycosidation reactions. Treatment of 3 with dibromomethyl methyl ether results in the formation of the labile β-furanosyl bromide 7 and the cyrstalline pyranosyl bromide 8 in a ratio of 1:2, both of which are further characterized by their methyl glycosides 10 and 11, respectively. Action of dibromomethyl methyl ether at room temperature on the benzyl ether 6, conventionally prepared from 3, is shown to proceed initially to the glycosyl bromide 9. Compound 9 is cleaved to the 4-formyl-blocked pyranosyl bromide 12, and only after prolonged reaction time gives the pyranosyl halide 8. The glycosidation of the glycosyl bromide 1 with benzyl-4–0-benzyl-α-D-olivoside 13 in the presence of silver carbonate and silicate is a sluggish reaction and gives rather low yields of the β-and the α, l-3-linked disaccharides 15 and 16 in the ratio 3–4:1. With silver triflate the yield is improved to the 61% and the ratio 6:1 in favour of 15.

Further transformations lead to both the syrupy olivosyl olivosides 17. and 18. In a more favourable reaction sequence 1 is condensed with the alcohol component 5 and silver triflate as promoter and yields the crystalline β-(19) and the α, 1→3-linked disaccharides (20) in 92% and a ratio of 6.5: 1. By subsequent transformations the protected title tetradeoxy disaccharide 21 is obtained.     

Halogenotropy in Phosphorus-Carbon Diad

Abstract

NMR and chemical studies have shown that α-halogenoalkyl-phosphines 1 and P-halogenoylids 2 exist as halogenotropic tautoineric systems. The position of the equilibrium depends on the used solvent, temperatures and substituents at the α-carbon atom. For example, the equilibrium 1 2 shifts towards the phosphine from 1 if the substituents at the α-carbon atom are electron-donating (R = H, Me, Pr, i-Pr). These compunds, existing preferably in the phosphine form, undergo typical reactions both for tervalent phosphorus compounds and P-halogenoylids. Tervalent phosphorus compounds, α-halogenoalkylphosphines 1 add sulfur and react with anhydrous HCl to convert into the dichlorophosphines -4. Like the P-halogenoylids, they add alcohols and phenols forming the phosphonium salts 5, 6, react with primary amines and aniline to yield the iminophosphonates 7 They also form the 2-halogenoalkylphosphonates 8 in the reaction with aldehydes.     

Synthesis of Potential Antimicrobial Agents from Maltose. III. Introduction of an Amino Group Into the 3′-Position of 1,6-Anhydro-Disaccharides

Abstract

Regioselective cleavage of 1,6-anhydro-maltose (1) with periodate and the subsequent recyclization with nitromethane gave 1,6-anhydro-3′-deoxy-3′-nitro-disaccharides (3). Three diastereomers, prepared by benzylidenation of 3, were separated by column chromatography. Each of 4′,6′-O-benzylidene derivatives successively underwent debenzylidenation, reduction of the nitro group, and peracetylation to give 3′-acetamido-3′-deoxy-disaccharide derivatives (7, 8, and 9). The configurations of the 3-amino sugar moietres in 7 (D-gluco), 8 (D-manno) and 9 (D-galacto) were determined on the basis of the ¹H NMR data. The main product (7) was further modified to the 6-deoxy-6-nitro derivative.     

Umpolung of α-Allenic Ketones and Esters by Phosphorus Groups

Abstract

Change in the regioselectivity of the addition of nucleophilic compounds YH (ROH, RSH, RNH₂) on α -allenic ketones and esters can be achieved by using the triphenylphosphonio group as an umpolung agent¹⁾. In this way α, β-unsaturated ketones and esters 4 are obtained with heteroatomic substituents in the γ position. The Umpolung scheme of the activated allene 1 is charaterized by a functional vinylphosphonium salt 2 as a synthetic equivalent of the a⁴-synthon 3.     

1-Thioglycopyranosyl Esters of N-Acylamino Acids

Abstract

Fully protected 1-thioglycopyranosyl esters of N-acylamino acids (5, 6, and 7) were prepared by condensation of methyl 2, 3, 4-tri-O-acetyl-1-thio-β-d–glucopyranuronate (1), 2, 3, 4-tri-O-acetyl-1-thio-l–arabinopyranose (2), and 2, 3, 4-tri-O-acetyl-1-thio-D-arabinopyranose (3) with pentachlorophenyl esters of N-acylamino acids in the presence of imidazole. The ¹³C NMR chemical shifts of the starting 1-thio sugars and the 1-thiol ester products are reported.