Synthetic methods for azaheterocyclic phosphonates and their biological activity.

We thank the Spanish Ministerio de Ciencia e Innovacion (Grant Nos. CTQ2007-65218 and Consolider Ingenio 2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER), and the University of Alicante for generous and continuous financial support.

/pdf/diastereoselective-allylation-of-carbonyl-compounds-and-2yzd9tlqi5.pdf

Diastereoselective allylation of carbonyl compounds and imines: application to the synthesis of natural products.

Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quaternary carbon atoms in their intricate structures are reviewed with 12 representative examples. Emphasis has been put on methods to create quaternary carbon stereocenters, including syntheses of the same natural product by different groups, thereby showcasing the diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quaternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information.

/pdf/synthetic-strategies-toward-natural-products-containing-20bttg89an.pdf

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms.

Propellanes are a unique class of compounds currently consisting of well over 10 000 representatives, all featuring two more or less inverted tetrahedral carbon atoms that are common to three bridging rings. The central single bond between the two bridgeheads is significantly weakened in the smaller entities, which leads to unusual reactivities of these structurally interesting propeller-like molecules. This Review highlights the synthesis of such propellanes and their occurrence in material sciences, natural products, and medicinal chemistry. The conversion of [1.1.1]propellane into bridgehead derivatives of bicyclo[1.1.1]pentane, including oligomers and polymers with bicyclo[1.1.1]penta-1,3-diyl repeat units, is also featured. A selection of natural products with larger propellane subunits are discussed in detail. Heteropropellanes and inorganic propellanes are also addressed. The historical background is touched in brief to show the pioneering work of David Ginsburg, Gunther Snatzke, Kenneth B. Wiberg, Gunter Szeimies, and others.

Propellanes-From a Chemical Curiosity to "Explosive" Materials and Natural Products.

Chlorine-containing natural compounds in higher plants

Structures of acutumine (XXXVIIa) and acutumidine (XXXVIIb), isolated from Menispermum dauricum DC. and Sinomenium acutum REHD. et WILS. (Menispermaceae), were investigated. On the basis of a series of degradative and spectroscopic evidences, their structures including absolute stereochemistry are assigned to the formula XXXVIIa and XXXVIIb, respectively, which are in good agreement with the result obtained from the X-ray analyses of acutumine and acetylacutumine. Apparently, these alkaloids represent a new class of alkaloids with a novel skeleton and also provide rare examples of chlorine-containing alkaloids.

Studies on the Alkaloids of Menispermaceous Plants. CCLIX. Alkaloids of Menispermum dauricum DC. (Suppl. 7). Structures of Acutumine and Acutumidine, Chlorine-Containing Alkaloids with a Novel Skeleton

To develop antagonists which show selectivity in blocking neurotransmitters, several aminophosphonoic acids, 2-amino-5-phosphonopentanoic acid (IVb), 2-amino-4-(2-phosphonomethylphenyl) butyric acid (VIII), 2-(2-amino-2-carboxy) ethylphenylphosphonic acid (XIc), and N-benzylproline-4-phosphonic acid (XIX), were synthesized. Compounds IVb, VIII, and XIc were prepared from the corresponding halides (V, Xa, and XIa, respectively) by treatment with sodium diethyl acetamidomalonate (VI). Compound XIX was synthesized via 1, 3-dipolar cycloaddition of ethyl N-benzyl-N-phenylthiomethylglycinate (XV) to diethyl vinylphosphonate (XVI).

Structural Modification of Bioactive Compounds. II. Syntheses of Aminophosphonoic Acids

1-Cinnamoylisoquinoline (I) was treated with perchloric acid in ethanol to give 2, 5-dihydro-1-oxo-3-phenyl-[1H] pyrrolo [2, 1-α] isoquinolinium perchlorate (V) in the yield of 48.1%. V was derived to 1-(4-nitrobenzoyloxy)-3-phenyl-[1H] pyrrolo [2, 1-α] isoquinoline (VI) by means of the Shotten-Baumann reaction. 3-Methylquinoxalin-2-yl 4-phenyl-1, 3-butadienyl ketone (VIIa) was treated with acid to give 3-hydroxy-4-methyl-1-styrylpyrrolo [1, 2-α] quinoxalinium perchlorate (VIIIa) in quantitative yield. VIIIa was treated with diazomethane to give 3-methoxy-4, 5-dimethyl-1-styrylpyrrolo [1, 2-α] quinoxalinium perchlorate (XI). VIIIa gave a monobromide (XIIa) on treatment with bromine in carbon tetrachloride. The rate of acid-catalyzed cyclization of 3-methylquinoxalin-2-yl 4-(4-nitrophenyl)-1, 3-butadienyl ketone (VIIb) was slower than that of VIIa. Attempts to cyclize XIV intramolecularly to 2, 5-dihydro-1-phenylpyrrolizin-3 [1H]-one (XVI) were unsuccessful under various conditions.

Acid-catalyzed Cyclization of Chalcones derived from Various Nitrogenous Heteroaromatic Compounds

Reactions of 2-acetyl-3-methylquinoxaline 1,4-dioxide and its derivatives

2-Methoxy-4, 4-dimethyl-2-cyclohexenone (II) afforded 5, 6-epoxy-6-methoxy-4, 4-dimethyl-6-hexanolide (III) upon reaction with m-chloroperbenzoic acid in 1, 1, 1-trichloroethane. On the other hand, the treatment of II with the same reagent in an aqueous disodium orthophosphate-methylene chloride system at 4°C gave 2, 3-epoxy-2-methoxy-4, 4-dimethylcyclohexanone (V), which could be converted to methyl 2-hydroxy-1-methoxy-3, 3-dimethylcyclopentanecarboxylate (VI). 2-Methoxy-4, 4-dimethyl-2, 5-cyclohexadienone (I) afforded 5, 6-epoxy-2-methoxy-4, 4-dimethyl-2-cyclohexenone (VIII) upon reaction with hydrogen peroxide in a basic medium. The reaction of I with m-chloroperbenzoic acid at room temperature gave 5, 6-epoxy-6-methoxy-4, 4-dimethyl-2-cyclohexenone (X). Neither VIII nor X gave the expected 2, 3, 5, 6-diepoxy-2-methoxy-4, 4-dimethylcyclohexanone (VII), but afforded 2, 3, 5, 6-diepoxy-6-methoxy-4, 4-dimethyl-6-hexanolide (IX).

Katsuhide Matoba

Papers

Studies on the Alkaloids of Menispermaceous Plants. CCLIX. Alkaloids of Menispermum dauricum DC. (Suppl. 7). Structures of Acutumine and Acutumidine, Chlorine-Containing Alkaloids with a Novel Skeleton

Structural Modification of Bioactive Compounds. II. Syntheses of Aminophosphonoic Acids

Acid-catalyzed Cyclization of Chalcones derived from Various Nitrogenous Heteroaromatic Compounds

Reactions of 2-acetyl-3-methylquinoxaline 1,4-dioxide and its derivatives

Chemistry of 2-Methoxy-2, 5-cyclohexadienones. II. Oxidation of 2-Methoxy-4, 4-dimethyl-2, 5-cyclohexadienone