Synthesis of (±)-4-Demtthoxy-7 11-Dideoxydaungmy-Cinone

Our continued interest in the total synthesis of natural and unnatural antitumor anthracyclines¹ especially the aglycones such as daunomycinone (1)² and 4-demethoxydaunomycinone (2),³ 11-deoxydaunomycinone(3)⁴ and 4-demethoxy-11-deoxydau-nomycinone (4)⁵ led us to investigate various methods for obtaining these products. Recently we have reported the synthesis of 4-demethoxy-7, 11-dideoxydaunomycinone (5) from 5-methoxy-1-tetralone. Now we wish to report the synthesis of 5 starting from 5-methoxy-1-tetralone (9) which was prepared from 1,6-dimethoxy-naphthalene(8). Umezawa⁷ et al. have reported the total synthesis of 4-demethoxy-ll-deoxydaunomycin(6) and 4-demethoxy-11-deoxy-adriamycin (7) from 5-methoxy-2-tetralone.     

Synthesis of peptide alkaloids-III. Amino acids and peptides-XXXII. Synthesis of dihydro-zizyphine A and B

Recently we described² a new cyclisation method for the synthesis of ansa peptides by hydrogenolysis of Z-pentafluorophenyl ester and ring closure on the surface of the palladium catalyst. We applied this reaction to the synthesis of the 14-membered ansa peptide dihydro-zizyphine G¹. Here we wish to report the synthesis of the 13-membered ansa peptides dihydro-zizyphine A ($\text{8a}$) and B ($\text{9a}$)³.     

Glycosylation Using Methylthioglycosides of N-Acetylneuraminic Acid and Dimethyl(Methylthio)Sulfonium Triflate

Abstract

Recently, great interest has been focussed on the synthesis of oligosaccharides containing N-acetylneuraminic acid (Neu5Ac) because of its important roles in a variety of biological recognitions.² However, many difficulties in the synthesis of naturally occurring α-glycosides still remained.³ We have recently reported the stereo-selective synthesis of a series of α- and β-2-thio-neuraminyl glycosides.^1-4

In the meantime, the utility of thioglycosides in oligosaccharide synthesis has been widely developed.⁵ Particularly noteworthy is the dimethyl(methylthio)sulfonium triflate (DMTST) promoted glyco-sylation method^5k.1 because excellent yields are achieved due to the high thiophilicity of this reagent.     

An Alternative Route to Yomogi Alcohol

On the basis of spectral data plus results of selective partial hydrogenation, yomogi alcohol, a new artemisia-type monoterpene originally considered to have structure I,¹ was reformulated as II.² Meanwhile, Willhalm and Thomas³ and later Thomas and Pawlak⁴ reported a nonselective synthesis of II along with a study of its chemistry. Independently, Sucrow⁵ developed a specific route to II and also a synthesis of I. Here we report an efficient, alternative two-step synthesis of II starting from 3,3-dimethylpent-1-en-4-yne (III).⁶     

Heterocycles in Organic Synthesis. III A Facile Synthesis of Isoquinolinyl Vinyl Sulphides

Vinyl sulphides find a substantial application in organic synthesis.² The synthetic utility of heter cyclic vinyl sulphides due to the ease in extension of heterocyclic ring³ should be more versatile, Here, we report the synthesis of isoquinolinyl vinyl sulphides from dihydrothiazolo [2, 3-a] isoquinolinium cations, depicting another use of heterocycles in organic synthesis.⁴     

A novel methodology for the synthesis of 1-desoxy-Δ-tetrahydrocannabinol (THC) analogues

A versatile and efficient sequence was developed for the synthesis of 1-desoxy-Δ⁸-THC analogues and is demonstrated by the synthesis of sulfonamide analogues with an acetylene group at the C-2^′ position in the side chain. In this procedure the 1-desoxy-Δ⁸- THC ring structure is built first and the synthesis of the side chain is then developed.     

Copper(II) Complexes of N-(Hydroxyethyl)Salicylideneimines

Abstract

Two groups of workers^1,2 have described the synthesis of Cu(sal:propanolamine). The compound is a dimer in chloroform and has a magnetic moment of 0.49 BM at room temperature.² There is no report in the literature on the synthesis of Cu(sal:ethanolamine). Apparently several groups have tried to synthesize the compound without success.^2,3 This communication describes the successful synthesis and characterization of Cu(sal:ethanolamine) and Cu(5-Br-sal:ethanolamine).     

Oligomannoside mimetics by glycosylation of 'octopus glycosides' and their investigation as inhibitors of type 1 fimbriae-mediated adhesion of Escherichia coli

The glycocalyx of eukaryotic cells is composed of glycoconjugates, which carry highly complex oligosaccharide portions. To elucidate the biological role and function of the glycocalyx in cell-cell communication and cellular adhesion processes, glycomimetics have become targets of glycosciences, which resemble the composition and structural complexity of the glycocalyx constituents. Here, we report about the synthesis of a class of oligosaccharide mimetics of a high-mannose type, which were obtained by mannosylation of spacered mono- and oligosaccharide cores. These carbohydrate-centered cluster mannosides have been targeted as inhibitors of mannose-specific bacterial adhesion, which is mediated by so-called type 1 fimbriae. Their inhibitory potencies were measured by ELISA and compared to methyl mannoside as well as to a series of mannobiosides, and finally to the polysaccharide mannan. The obtained results suggest a new interpretation of the mechanisms of bacterial adhesion according to a macromolecular rather than a multivalency effect.     

Synthesis in the Emetine Series XV1) Friedel-Crafts Acylation of N-Acetylhomoveratrylamine: A Facile Synthesis of 9,10-Dimethoxybenzo[a]Quinolizidine

Benzo[a] quinolizidines are important intermediates in the synthesis of Ipecac alkaloids³ and several representatives of this class are useful therapeutic agents.^4,5,6,7,8 We would like to report a new and versatile synthesis of the known quinolizidine derivative 8 ⁹ by a procedure which can easily be extended to the preparation of analogs and homologs.¹⁰     

Syntheses and CD‐Spectroscopic Investigations of Longer‐Chain β‐Peptides: Preparation by Solid‐Phase Couplings of Single Amino Acids,Dipeptides, and Tripeptides

The synthesis and CD‐spectroscopic analysis of eleven water‐soluble β‐peptides composed of all‐β³ or alternating β²‐ and β³‐amino acids is described. Different approaches for the efficient syntheses of longer‐chain β‐peptides (>9 residues) were investigated. They were synthesized on solid phase with Fmoc‐protected amino acids or Fmoc‐protected di‐ or tripeptide fragments (assembled using solution‐phase synthesis). The use of preformed fragments significantly increased the purity of the crude peptides and facilitated purification. Especially, the use of Fmoc‐protected β²/β³‐dipeptides for the synthesis of a ‘mixed' β²/β³‐nonapeptide proved to be remarkably effective, yielding the crude peptide in 95% purity and without detectable epimerization of the β²‐amino acid residues. This is a significant improvement over previously reported procedures for the solid‐phase synthesis of β‐peptides, and foreshadows that the field of β‐peptide research will now switch from synthesis to the design and study of complex functional ‘β‐proteins'.     

A highly efficient synthesis of [1-C, O]- and [1-C, H2]-glycerol for the elucidation of biosynthetic pathways

Labeled glycerol is a widely used biochemical probe to investigate biosynthetic pathways. A highly efficient synthesis of [1-¹³C, ¹⁸O]- and [1-¹³C, ²H₂]-glycerol is described in which the ¹³C label is introduced using cyanide. The ¹⁸O label was introduced by a Pinner synthesis and reduction of the ester 5 allowed incorporation of the ²H labels.     

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).     

The synthesis of 2,6-dimethylenetricyclo[3.3.0.03,7]octane

The synthesis of the title compound is reported together with that of 2-methyl-6-methylenetricyclo[3.3.0.0^3,7]octane. During the synthesis a rearrangement of the tricyclo[3.3.0.0^3,7]octane skeleton to the tricyclo[3.2.1.0^3,6]octane system has been observed.     

The “Speedy” Synthesis of Atom‐Specific 15N Imino/Amido‐Labeled RNA

Although numerous reports on the synthesis of atom‐specific ¹⁵N‐labeled nucleosides exist, fast and facile access to the corresponding phosphoramidites for RNA solid‐phase synthesis is still lacking. This situation represents a severe bottleneck for NMR spectroscopic investigations on functional RNAs. Here, we present optimized procedures to speed up the synthesis of ¹⁵N(1) adenosine and ¹⁵N(1) guanosine amidites, which are the much needed counterparts of the more straightforward‐to‐achieve ¹⁵N(3) uridine and ¹⁵N(3) cytidine amidites in order to tap full potential of ¹H/¹⁵N/¹⁵N‐COSY experiments for directly monitoring individual Watson–Crick base pairs in RNA. Demonstrated for two preQ₁ riboswitch systems, we exemplify a versatile concept for individual base‐pair labeling in the analysis of conformationally flexible RNAs when competing structures and conformational dynamics are encountered.     

A Convenient Preparation of 2-Ethyl-4-Carboxycyclohexanone

Several years ago in the course of work directed toward the total synthesis of the iboga alkaloids¹, we required relatively large quantities of 2-ethyl-4-carboxycyclonhexanone (1) and its methyl ester as precursors to 3-ethyl-5-carbomethoxycyclohexene. Although it was possible to prepare keto acid 2 from 1,3,5-tricarbomethoxypentane (3) following the published synthesis of 2-methyl-4-carboxycyclohexanone², the overall yield was only 52%. ³ In addition, the isolation and purification of intermediates 4 renders the synthesis rather tedious.     

Synthesis and properties of magnetic fluids produced on the basis of magnetite particles

Magnetic fluids based on magnetite synthesized by the chemical condensation method at temperatures of 25, 40, 60, and 80°C were obtained and studied. Magnetite particles were examined by X-ray phase and X-ray fluorescence analyses and electron microscopy. The average size of the coherent scattering region of magnetite particles was 13–17 nm, depending on the synthesis temperature. Magnetic fluids were synthesized from magnetite particles obtained at 25 and 80°C, with water and octane serving as carrier fluids. The NMR method was used to determine the saturation magnetization and average magnetic moment of the particles: for water-based magnetic fluids, 2100 A m^–1 and 5.7 × 10^–19 A m² at magnetite particle synthesis temperature of 25°C and 3670 A m^–1 and 4.6 × 10^–19 A m² at magnetite particle synthesis temperature of 80°C; for octane-based magnetic fluids, 2250 A m^–1 and 4.1 × 10^–19 A m² at magnetite particle synthesis temperature of 25°C.     

Synthesis of 1-TRiacontanol

Several studies describing the synthesis of 1-triacontanol have appeared¹ following the report² that application of 1-triacontanol (1), an active constituent of alfalfa (Medicago sativa L.), increased the yields of tomatoes, cucumber, lettuce, rice, corn and several other crop species. We detail here a convenient synthesis of 1-triacontanol, and the salient feature of this synthesis is that these reactions are inexpensive, simple and amenable to multigram synthesis.     

A Novel Synthesis of the Yohimbane Skeleton-Course of the Synthesis of 15,16,17,18,19,20-Hexadehydroyohimbane by Use of Palladium Catalyzed Insertion of Carbon Monoxide

In the course of our continuing synthetic experiments on benzoquinolizidine² and indoloquinolizidine alkaloids³, we have recently utilized palladium catalyzed amidation⁴ for the synthesis of the berbine alkaloids⁵. In this present paper we wish to report, what we believe is the first successful utilization of the palladium catalyzed amidation for the synthesis of the hexadehydroyohimbane skeleton.     

A General Synthesis of α-Substituted Acrylic Esters

During a study of synthetic approaches to various naturally-occurring sesquiterpenes lactones, we developed a new synthesis of the α-methylene-γ-butyrolactone group.¹ This new sequence suggested that it might be applicable to the general synthesis of α-methylenecarbonyl compounds.² This report describes the application to a general synthesis of α-substituted acrylic esters.     

The Synthesis of 4,5-Acetylenic Prostaglandins

The synthesis of cis-Δ⁴ prostaglandins has been reported.¹ The conversion of these Δ⁴ analogs to 4,5-acetylenic prostaglandins can be accomplished via the bromination-dehydrobromination procedure reported earlier.² A new approach to the synthesis of 4,5-acetylenic prostaglandins via readily available intermediate has been developed. We wish to report herein this general approach.³