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.     

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.     

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 Dimethoxyfuranonaftoquinones

Recently some furanonaphthoquinones were isolated from Tabebuia species^2,3,4. The structures la, lb2, and li4 were assigned to three of these compounds (those of la and lb being later confirmed by synthesis^3,5,6). However, for the three other isolated compounds the spectroscopic data did not permit a decision to be made between the 2,3,4 - - - 4 isomeric pairs of structure lc and Id, le and lf ³, and lg and lh ⁴. Compounds la, lb, and le (or If), were tested in the KB cell culture assay and shown to be more active cytotoxic agents than lapachol^2,3, the probable biogenetic precursor of all of them.     

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.     

Useful Synthesis of Coumestans

A convenient synthesis of coumestans involving a combination of lithiation and Wittig reactions is described. Compounds 1a and 1b on reaction with n-butyllithium followed by treatment with diethyloxalate provide ketoesters 3a and 3b. Reaction of 3(a-b) with phosphorane generated from salt 4 gives 5(a-b) which on reaction with pyridine hydrochloride yield 7(a-b). DDQ oxidation of 7(a-b) gives coumestans 8(a-b).     

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.     

Synthesis and Structure Elucidation of 8-Methyl- and 9-Methyl-exo-2-carbomethoxy-endo-tricyclo[5.2.1.02,6]deca-3,8-dien-5-ones

A mixture of 1-methyl- and 2-methyl-1,4,4a,8a,-tetrahydro-endo-1,4-methano-naphthalene-5,8-diones ( 2 & 3 ) was chemically transformed into separable methyl substituted tricyclo[5.2.1.0^2,6]decadienones 7 , 8 & 9 . The structure of 8 & 9 were elucidated via Cope rearrangement of their corresponding allylic alcohols ( 10 & 11 ) to furnish 12 & 13 respectively.     

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.     

Diborane Reduction of O-(Tert-Butyldimethylsilyi.)galactaramides. A Model Study for Aminoalditol Synthesis

Tert-butyldimethylsilylation of dimethyl galactarate (1) with tert-butylchlorodimethylsilane/imidazole/N,N-dimethylformamide at 25 [ddot]C dimethyl 2,5-bis-O-(tert-butyldimethylsilyl)galactarate (2) as the principal product, with methyl 2,3,5-tris-O-(tert-butyldimethylsilyl)-D,L-galactarate-l,4-lactone (3) and methyl 2,3-bis-O-(tert-butyldimethyl)-D,L-galactarate-l,5-lactone (4) as minor products. When the reaction was carried out at 65 [ddot]C, the only product was the 1,4-lactone, 3 Ammonolysis of 2 in methanol gave 2,5-bis-O-(tert-butyldimethyl)-galactaramide (5, 94%), which was conveniently reduced with borane- THF to 1,6-diamino-1,6-dideoxygalactitol, isolated as its dihydrochloride 9. Ammonolysis of 3 in methanol gave a mixture of 5; 2,3,4-tris-O-(tert-butyldimethylsilyl)-D,L-galactaramide (6), 2,3,5-tris-O-(tert-butyldimethylsilyl)-D,L-galactaramide (7), and 2,3,5-tris-Q-(tert-butyldimethylsilyl)-D,L-1,4-lactonogalactaramide (8). Borane-THF reduction of a mixture of 6 and 7 also yielded 9. This study served as a model for the use of O-silylated carbohydrate amides in the preparation of aminodeoxyalditols.     

Synthesis of Glycosyl Cyanides and C-Allyl Glycosides by the use of Glycosyl Fluoride Derivatives

A treatment of 2,3,5-tri-O-benzyl-B-D-ribofuranosyl fluoride (1) with cyanotrimethylsilane in the presence of boron trifluoride diethyl etherate gave 2,3,5-tri-O-benzyl-α- (2α) and -β-D-ribofuranosyl (2β) cyanide in 46.2% and 46.6% yields, respectively. Confirmation of the corresponding isocyano isomer (3) formation and its conversion into 2 under boron trifluoride catalysis at -78°C made it possible to deduce that both 2α and 2β were produced by way of 3 which was formed preponderantly in the initial stage of the reaction. On the other hand, the reaction of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride (4) with cyanotrimethylsilane in diethyl ether by the use of boron trifluoride diethyl etherate (0.05 mol. equiv.) gave 2,3,4,6-tetra-O-benzyl-α -D-glucopyranosyl cyanide (5α), 2,3,4,6-tetra-O-benzyl-α- (6α), and -β-D-glucopyranosyl isocyanide (6β) as a 30:61:9 mixture (94% yield) but that in dichloromethane by the use of the catalyst (1.0 mol. equiv.) gave 5α (85% yield) as a sole product.

The reactions of 1 and of 4 with allyltrirnethylsilane under the same catalysis afforded C-allyl 2,3,5-tri-O-benzyl-α-D-ribofuranoside (7)(93.5% yield), and C-allyl 2,3,4,6-tetra-O-benzyl-α- (8α)(71.8% yield) and -β-D-glucopyranoside (8β) (22.4% yield), respectively.     

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.     

Synthesis of Gentamine C1a from Neamine Using Ionic Displacement and Radical Elimination Methods

Abstract

The conversion of tetra-N-benzyloxycarbonyl-5,6-O-cyclohexylidene neamine (8) into the corresponding olefin 13 has been investigated by three methods. Application of the Tipson-Cohen procedure via the dimesylate 10 gave a low yield (22%), as did the reaction of the diol 8 with triphenylphosphine-iodine-imidazole reagent (42%). Contrastingly, reductive radical elimination via the dixanthate 11 gave a synthetically useful yield (64%) without any chromatographic purification.     

An Improved Synthesis of 1-Alkyloxycarbonyl 3-Ethyl-3-Hydroxy 1,2,3,6-Tetrahydropyridine. An Intermediate in the Synthesis of Aspidosperma Type Indole Alkaloids

Imanishi and co-workers¹ reported recently a procedure giving access to the title compound 5 (R=Et) which was used as a key intermediate for a formal synthesis of the Aspidosperma alkaloid tabersonine. As part of a broad synthetic programme of elaborating Aspidosperma and/or Iboga type indole alkaloids via cyclo-addition reactions^2,3 between indole-2-acrylates and suitably substituted di-and tetrahydropyridine we became interested in compounds analogous to 5. The present paper describes an alternative route to 5 (R=Et) as outlined in the following scheme.     

A Facile Synthesis of 2-Hydroxy-6-Methylacetophenone

Recently, we identified 2-hydroxy-6-methylacetophenone (3) and 2-acetoxy-6-methylacetophenone (4) as exocrine compounds in several neotropical species of ants in the dolichoderine genus Hypoclinea. Although 3 has been reported at least four times in the literature as a synthetic intermediate or as the object of a nuclear magnetic resonance study, neither 3 nor 4 had been reported as natural products, and 4 is a novel compound.^2,3,4,5     

A Convenient Synthesis of 3-Deoxy-D-gluco-2-octulosonate (D-gluco-KDO)

β-Lithiated acrylates have proven to be versatile pyruvate β-carbanion equivalents which are also useful in D-manno-KDO synthesis. The secondary amine adducts of acetylenedicarboxylate 4 display the same versatility, as demonstrated in this paper. However, on reaction with 2,3:4, 5-di-O-isopropylidene-D-arabinose 6, the diastereofacial selectivity is in favor of the gluco-isomer, thus leading with lithiated compounds 4A, preferentially to α-aminobutenolides 7-(g). The best results were obtained with the morpholine adduct of di-tert.-butyl acetylenedicarboxylate 4d which afforded the gluco-isomer 7d-(g) as an easily separable crystalline material. Its deamination and concomitant deisopropylidenation with trifluoroacetic acid provided the known α-hydroxy-butenolide 8b-(g), which was transformed via decarboxylation product 9-(g) to D-gluco-KDO 10-(g) thus concluding a convert four step synthesis of this compound via crystalline intermediates.     

A Convenient Synthesis of 3-Methoxyphthalic Anhydride

Many antibiotics of the anthracycline family¹ possess structures for which 3-methoxyphthalic anhydride (1) would be a suitable synthon² in a total synthesis. A classic synthesis of (1) has employed 3-nitrophthalic acid³ but, in our hands, proceeded in low overall yield. Recent syntheses have utilized the Diels Alder reaction of dimethyl acetylenedicarboxylate (2) with 1-methoxy-1,3-cyclohexadiene,⁴ 1,4-diacetoxybutadiene,⁵ 2-acetoxyfuran,⁶ 2-methoxyfuran⁷ or furan⁸ to obtain 3-hydroxyphthalic acid or a derivative. We now wish to report a convenient Diels-Alder synthesis of (1) from 3-methoxy-2-pyrone (3).     

A Comvewiemt Synthesis of 1-Aminopolycycloalkames and Their Tosylate Salts

Syntheses of oridgehead 4-amino-l-bromopentacy-clo[4.3.0.0^2.5 O^3,8.O^4,7]nonan-9-one ethyl ene acetal (6), 4-iodocubyl-l-ammonium tosylate (8) and 1-adamantane ammonium tosylate (10) are described.     

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.     

Aminohaloborane in Organic Synthesis. V.1 An Aldol-Type Condensation of Acetonitrile and Phenylacetonitrile with Benzaldehydes Using Secondary Aminodichloroborane

3-Phenyl-3-sec-aminopropionitriles (1) are not found in literature. We describe here a simple synthesis of 1 from acetonitriles (2) and benzaldehydes (3) using sec-aminodichloroboranes (4)² and triethylamine (5).