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.     

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     

A Total Synthesis of (±)-Trichodiene

Trichodiene (1), a sesquiterpene hydrocarbon, was isolated from the extract of mycelium of Trichothecium roseum. The structure of trichodiene (1) was elucidated by Nozoe and Machida in 1970 via degradation and spectroscopy.¹ Trichodiene (1) has been shown to be the biogenetic precursor of the trichothecane family of sesquiterpenoids as characterized by the cytotoxic fungal metabolite (-)-trichodermin (2).^2,3 The structure and absolute stereochemistry of (-)-trichodermin (2) were determined by X-ray diffraction and, therefore, the structure and absolute stereochemistry of trichodiene (1) are now firmly established.⁴ We wish to report a total synthesis of (±)-trichodiene (1) via previously reported lactone 3.^5,6     

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 N-Alkyl-N'-cyano-N″-4-pyridylguanidines from 4-Pyridyldithiocarbamic Acid via N-Alkyl-N′-4-Pyridylthioureas,or via 4-Pyridylcyaniminothiocarbamic Acid

Several years ago a number of antihypertensive N-alkyl-N′-cyano-N″-pyridylguanidines was prepared by addition of cyanamide to N-alkyl-N′-pyridylcarbodiimides which were obtained from the respective thioureas and phosgene or triphenylphosphine/carbon tetrachloride¹. Recently we have described some attractive synthetic methods for N-alkyl-N′-4-pyridylthioureas², based on 4-pyridyldithiocarbamic acid (1) (Scheme 1). We now report on the synthesis of N-alkyl-N′-cyano-N″-4-pyridylguanidines (4) from (1) by two different routes which ultimately may pass through a common intermediate (3) (Scheme 1).     

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.     

A Convenient Synthesis of (Z)-7-Nonadecen-Ll-One and (Z)-7-Eicosen-Ll-Cne -the Pheromones of Peach Fruit Moth

In 1977 Tamaki¹ et al have isolated and synthesized² (Z)-7-nonadecen-ll-one (la) and (Z)-7-eicosen-l1-one (1b) which are active components of the female sex pheromones of the peach fruit moth Carposina niponensis Walsingham, a major economic pest of apple, peach and other fruits of Japan. We report in this communication a practical, convenient and stereospecific route to 1a and 1b.     

The Reaction of N-Phenyliminoketenylidenetriphenyl-phosphorane with α,β-Unsaturated Carbonyl Compounds. Synthesis of New Pyran Derivatives

Abstract

The reaction of N-phenyliminoketenylidenetriphenylphosphorane [a] (1), with 2-benzylidene-1, 3-indandione (2), 1,2-diphenyl-3,4-pyrazolidenedione (3)and/or 5-benzylidene barbituric acid (4) has been investigated. When ylide 1 was allowed to react with compounds 2, 3 or 4 in THF at ambient temp. the corresponding new pyrano-phosphoranylidenes 5, 6 or 7 were obtained. The elemental microanalyses, IR, ¹H NMR, ³¹P NMR and MS data agree with the structure of the cyclic iminophosphoranes by [4+2]-cycloaddition and exclude 4-membered ring structure by [2+2]-cycloaddition. When the Wittig reaction was carried on the pyrano-phosphoranes 5, 6 or 7 using p-nitrobenzaldehyde, the exocyclic olefins together with triphenylphosphine oxide were isolated.     

Synthesis of Coleon U

The recent publication by Matsumoto¹ of a synthesis of Coleon U²(1) prompts us to present our own preparation of this poly-hydroxy diterpene as the tri-O-methyl (12a) and tetra-O-methyl ethers (12b). In a previous communication³ we outlined our approach which is aimed at several similar natural products such as Coleon C⁴ (1b), Lycoxanthol⁵ (2), etc. and differs considerably from that of the Japanese group. Formally at least, the two syntheses start with the same material, (+) ferruginol methyl ether 5a. In our case the latter was prepared by recorded methods from methyl O-methyl podocarpate after introducing the iso-propyl sidechain⁶ (→4), transforming the C.4 methoxycarbonyl residue to a methyl⁷ (→5a, ferruginol methyl ether) which was oxidised at the benzylic position of the B ring to give sugiol methyl ether 5b.     

Synthesis of Retro-γ-Ionols and the Corresponding-Ionones1

Both the direct² and the sensitized^3,4 photolyses of (E)-β-ionol (2) have been studied in some detail. In a preliminary publication⁵ we have indicated that direct photolyses of (E)-β-ionol (2) with λ = 254 nm yields (Z)-retro-γ-ionol (3) as the primary product; upon further irradiation 3 is converted into the corresponding (E)-isomer (4) which rapidly yields the bicyclic alcohol 5. A quantitative study revealed that the photoconversion of (E)-β-ionol with λ = 254 nm to 3 is about 10 times faster than the conversion of 3 into (E)-retro-γ-ionol.⁶ This rate difference thus allows the photosynthesis of 3.     

Synthetic Mucin Fragments: Methyl-3-O-(2-Acetamido-2-Deoxy-4-O- and 6-O-β-D-Galactopyranosyl-β-D-Glucopyranosyl)-β-D-Galactopyranoside and Methyl 3-O-(2-Acetamido-2-Deoxy-4-O- and 3-O-Methyl-β-D-Glucopyranosyl-3-D-Galactopyranoside

Abstract

Glycosylation of methyl 3-O-(2-acetamido-3, 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (1), catalyzed by mercuric cyanide, afforded a trisaccharide derivative, which was not separated, but directly O-deacetylated to give methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-giucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (8). Hydrogenolysls of the benzyl groups of 8 then furnished the title trisaccharide (9). A similar pflyccsylation of methyl 3-O-(2-acetamido-3-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl- β-D-galactopyranoside (obtained by acetylation of 4, followed by hydrolysis of the benzylidene acetal group) with bromide 1 gave a tribenzyl trisaccharide, which, on catalytic hydrogenolysls, furnished the isomeric trisaccharide (12). Methylation of 4 and 2 with methyl iodide-silver oxide in 1:1 dichloro-methane-N, N-dimethylformamide gave the 3-O- and 4-O-monomethyl ethers (13) and (15), respectively. Hydrogenolysis of the benzyl groups of 13 and 15 then provided the title monomethylated disaechartdes (15) and (16), respectively. The structures of trisacchacides 9 and 12, and disaccharides 14 and 16 were all established by ¹³C MMR spectroscopy.     

Synthesis of Bioactive Pyrethroid, 3-Phenoxybenzyl 1R-trans-2, 2-Dimethyl-3-(2-chloro-1-propenyl) Cyclopropanecarboxylate

The title compound 1 has been prepared from (+)-3-carene (2) and found to have the same order of activity as its IR-cis isomer 3 reported by us earlier¹ The key intermediate methyl IR-trans-2, 2-dimethyl-3-(2-oxopropyl)cyclopropanecarboxylate (4) has been characterised.     

The structure of cis and trans lsomers of 1-(p-Bromobenzylidene)-2-indanone

Abstract

In this communication we wish to report an interesting case of the isolation and characterization of the cis and trans isomers of 1-(p-bromobenzylidene)-2-indanone and their ketals. Prior to this work, Hoogstreen and Trenner² had reported on the cis and trans isomers of 1-(p-chlorobenzylidene)-2-methyl-5-methoxyindenylacetic acid. The condensation of 2-(N-morpholinyl)-indene (1, prepared by the reaction of 2-indanone³ and morpholine) with P-bromobenzaldehyde was conducted by refluxing them in the presence of acetic acid for 4 hours. Acid hydrolysis of the reaction mixture followed by dry column chrcmatography over sillica gel using a fraction collector afforded two iscmeric monobenzylidenes, compounds 2(36.6%, mp 110–111°)and 3(1.3%, mp 115–116°) and a dibenylidene, compound 4 (8.7%, mp 205°). The relative rations of the mono- and dibenzylidenes seemed to depend on the reaction conditions. Higher yields of the monobenzylidenes 2 and 3 were obtained by conducting the reaction in the presence of UV light. The structures of these monobenzylidenes were established as cis and trans isomers of 1-(p-bromobenzylidenes)-2-indanone on the Basis of elemental analyses and ir and nmr spectroscopy. The ir spectra⁴ (CHCl₃)

of compounds 2 [1725 (c=0), 1620 (c=c)cm^?1] and 3[1710 (c=o), 1570, 1600 (c=c) cm^?1] were consistent with the structures. The molecular ion peaks as well as the fragmentation patterns in the mass spectra of both these compounds were consistent with the assigned structures. Before going into the omr discussion it should be pointed out that treatment of compound 2 with athylene glycol in the presence of p-toluene sulfonic acid produced two ketals, 5 (38.3% mp, 118–120°) and 6 (30.6% mp, 125–126°). As depicted; the ketals 5and 6 were also found (by omr) to be related to each other as cis and trans isomers. Furthermore, each of them could be hydrolyzed with acid to the corresponding monobenzylidenes 2 and 3 without any isomerization. However, UV irradiation of compounds 2 and 3 gave equilibrium mixtures containing both the isomers, indicating isomerization had occurred under photolytic conditions.     

Synthesis of Some Non-Conjugated Dienones in the Retro-α-Ionone Series1

In the course of a study on the photochemical and thermal behaviour of β,γ-δ,ε-dienones^1-4, (E)-retro-α-ionone (2a) and a series of methylated (3, 4) and desmethyl analogues (2b-2e) have been synthesized by a simple deconjugative isomerization of the corresponding conjugated dienones in strong alkaline solution. 3-Methyl- (3) and 3,3-dimethyl-retro-α-ionone (4) have been prepared by addition of methyl chloride to a strongly alkaline solution of β-ionone (1a).⁵     

Oxidation of Cyclic Hemiacetals into Diketones: Final Steps in the Conversion of a Triterpenoid Ring a into a Steroidal Enone by a New Short Route

As a part of our studies in the conversion of triterpenoids into steroids we have reported¹ that the Jones oxidation of some triterpenoid hemiacetals (1) gives acyloxy acids (2) instead of the desired 1,5-diketones (3). We now report² the shortest route yet for the reconstruction of a triterpenoid ring A ketone (4) into a steroidal enone (7) involving as key steps the exhaustive Baeyer-Villiger oxidation³ of triterpenoid ketones (4) into δ-lactones (5) and mild chromium(VI) oxidation of cyclic hemiacetals (1) into diketones (3).     

(S)-(−)-2-Methyl-2-Phenylsuccinic Anhydride,a Novel Resolving Reagent and its Application to Resolution of CIS-5-Amino-4-Phenyl-1,3-DIOXANE

Abstract

A new resolving reagent, (S)-(?)-2-methyl-2-phenylsuccinic anhydride (5) for the resolution of amines via covalent bond formation and its application to the resolution of aminodioxane (±)-(1) is described. The d.e. of the amides (7) and (8) has been determined by studying ¹H-NMR spectra.     

An Efficient Stereoselective Synthesis of a Tricyclic Intermediate for the Synthesis of Derivatives of Abietic and Podocarpic Acids

For many years the synthesis of diterpene acids has attracted the attention of organic chemists. Kröniger and Wheeler¹ reported that the condensation of the dimethylate 1a with methyl malonate gave the cis compound 2a which on heating with palladised charcoal was converted into the trans isomer 3a. Compound 3a is a promising intermediate in the synthesis of derivatives of both abietic and podocarpic acids, while 2a could be a starting material for the synthesis of cis fused diterpene acids. However, the route to 2a and 3a was inefficient; 1a was only available as the minor component of a mixture with its epimer 1b; and the yield for the stage 2a + 3a was poor.     

A Stereoselective and Regioselective Total Synthesis of (π)-Trichodiene

Trichodiene (1), a sesquiterpene hydrocarbon, was isolated and characterized by Nozoe and Machida in 1970.¹ Trichodiene (1) has been shown to be the biogenetic precursor of the trichothecane family of sesquiterpenoids characterized by the cytotoxic fungal metabolite (–)-trichodermin (2).^2,3 We recently reported a total synthesis of (±)-trichodiene (1) via lactone 3.⁴ Now, we wish to report another stereoselective total synthesis of (±)-trichodiene (1) via lactone 3 which is highly regioselective.     

Monomeric and Dimeric (Aminomethylidene)phosphines and -Arsines

Abstract

In (dimethylaminomethylidene)phosphines (1) [1] and -arsines (2) the internal rotation of the dimethylamino group is hindered by a barrier of 50 to 55 kJmol^?1? analogous to the corresponding amidines. In order to evaluate the influence of this conjugative effect upon the P=C and (P)-C-N bond lengths, single crystal x-ray structure determinations of 1a and 2a have been carried out. For comparison, the cyclic (aminomethylidene)phosphine 1H-1,3-benzazaphosphole 5 [2] as well as the dimeric compounds 3a, 3b, and 3c [3] have been analyzed, too, while the arsenic derivative 6 was studied by others [4]. The diarsetanes 4 could not yet be isolated. The structural results indicate the E=C bonds in 1a, 2a, 5, and 6 to be scarcely elongated, the (E)-C-N bonds, however, to be shortened considerably with respect to the dimers.     

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.