5,8-isoquinolinediones. II. Chemical and electrochemical behavior of the 5,8-isoquinolinedione system

We have devised two general synthetic schemes to 5,8-isoquinolinediones and have investigated the chemical and electrochemical behavior of these compounds. The 1,4-addition reactions of these quinones with amines was shown to occur at the 7-position and a number of 7-amino-5,8-isoquinolinediones. were synthesized. The 1,4-addition of hydrogen bromide was also studied. The ethylenic double bond of the 5,8-quinone system underwent Diels-Alder additions to yield the oxidized forms of the adducts. The nucleophilic displacement of the methoxy group in 7-methoxy-5,8-isoquinoline was accomplished with both potassium hydroxide and morpholine. A Polarographic study of the half-wave potentials of substituted 5,8-isoquinolinediones showed a linear correlation between the change in the half-wave potential of the quinone system (ΔE° 1/2) resulting from the introduction of different substituents, and the substituent constants (σ_p-x).     

Crystal and molecular structure of aN(2)-benzyl-1,3-disubstituted-1,2,3,4-tetrahydro-β-carboline

(1R,3S)-2-Benzyl-3-methoxycarbonyl-1-methylcarboxymethyl-1,2,3,4-tetrahydro-9H-pyrido [3,4-b] indole, C₂₃H₂₄N₂O₄, was synthesized by a modified Pictet-Spengler reaction, and its crystal and molecular structure determined by single crystal X-ray diffraction methods. The crystals are monoclinic:P2₁ (No. 4),a=11.336(1),b=8.919(1),c=10.314(1)Å,=100.81(1)°,Z=2. The structure has been solved by direct methods, and refined toR=0.041 for 2203 observed reflections. The six-membered heterocyclic ring is in a half-chair conformation, and the substituents at C(3) and C(5) occupy axial and equatorial positions respectively. The CH₂Ph group attached to N(4) is in the generally less favoured axial position. The nitrogen atom of the indole system forms an intermolecular hydrogen bond with the carbonyl oxygen of the CH₂CO₂ Me group, the NO distance being 2.995(3)Å.     

Hetero-Diels-Alder and pyroglutamate approaches to (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid

The stereoselective syntheses of fully protected (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid, a non-coded amino acid of cyclomarin A, and its diastereomer are reported. A pyroglutamate template was employed in the key diastereoselective alkylation used for introducing the 4-methyl stereochemistry. In addition, the first diastereoselective intramolecular hetero-Diels-Alder of a 2-cyano-1-azadiene with an electron deficient dienophile is described.     

Stokes flow inside and around a fluid drop distorted by the presence of a tube wall

Using a quadratic optimisation process to satisfy the boundary conditions, the drag coefficient and the flow patterns inside and outside a fluid drop translating axially in a tube have been determined accurately even when the drop is clearly elongated. Convincing comparisons with experimental results (flow visualizations, velocity and drag measurements) are presented. The effects of the viscosity and density ratios are examined.     

Shape preserving polynomial curves

We introduce particular systems of functions and study the properties of the associated Bézier-type curve for families of data points in the real affine space. The systems of functions are defined with the help of some linear and positive operators, which have specific properties: total positivity, nullity diminishing property and which are similar to the Bernstein polynomial operator. When the operators are polynomial, the curves are polynomial and their degrees are independent of the number of data points. Examples built with classical polynomial operators give algebraic curves written with the Jacobi polynomials, and trigonometric curves if the first and the last data points are identical.     

Total synthesis of milbemycins: a synthesis of (6R)-6-hydroxy-3,4-dihydromilbemycin E

Following studies using benzyloxymethyl isopropenyl ketone 5 and ethyl 3-(3-furyl)-3-oxopropanoate 6, Robinson reactions between aryloxymethyl isopropenyl ketones 19 and 5 and ethyl 3-(2-trimethylsilyl-3-furyl)-3-oxopropanoate 20 were found to be stereoselective giving cyclohexanones 21 and 41, in which the 3-(arylmethoxy) substituents were cis to the 2-hydroxyl groups, as the major products. After reduction and protection of ketone 21, selective PMB-deprotection, oxidation and stereoselective reduction inverted the configuration at C3 to give the diol 30. Protection of the secondary 3-hydroxyl group followed by modification of the protected 4-alcohol then gave the hydroxybutenolides 36 and 37 after oxidation of the silylated furan using singlet oxygen. The 3-benzyloxycyclohexanone 41 was also converted into the hydroxybutenolide 37 via the (2-trimethylsilylethoxy)methyl (SEM) ether 35. The Wittig reaction between the ylid generated from 2-methylpropyl(triphenyl)phosphonium salt and hydroxybutenolide 36 gave predominantly the (2Z,4Z)-dienyl acid 38 which was taken through to the butenolide 40. Similarly, the racemic hydroxybutenolide 37 was condensed with the racemic ylid derived from phosphonium salt 53 to give, after SEM-deprotection and 5-membered lactone formation, a mixture of the (9Z,2'Z)-dienyl lactones 58 and 59 containing ca. 10% of the corresponding (9Z,2'E)-isomers 60 and 61. (2'Z)/(2'E)-Isomerisation of the dienes 58 and 59 using iodine followed by deprotection gave a mixture of the seco-acids 62 and 63. Selective macrocyclisation of the seco-acid 62 in which the relative configuration of the C1-C7 and C17-C19 fragments (milbemycin numbering) corresponded to that present in the natural milbemycins, gave the beta-milbemycin analogue 65 after butenolide reduction. The hydroxybutenolide 37 was also condensed with the ylid derived from the phosphonium salt 1 and the product taken through to (6R)-6-hydroxy-3,4-dihydromilbemycin E 77. Preliminary attempts to convert the beta-milbemycin analogues 65 and 77 into tetrahydrofurans corresponding to analogues of alpha-milbemycins by treatment with toluene p-sulfonyl chloride under basic conditions gave the primary allylic chlorides 78 and 79.     

A convergent total synthesis of ustiloxin D via an unprecedented copper-catalyzed ethynyl aziridine ring-opening by phenol derivatives

[reaction: see text] The ustiloxins are a family of heterodetic cyclopeptides that have been isolated from the water extracts of false smut balls on the panicles of rice plants caused by the fungus Ustilaginoidea virens. A concise total synthesis of ustiloxin D has been achieved via an unprecedented ethynyl aziridine ring-opening of phenol derivatives. The longest linear sequence of the synthesis is 15 steps from commercially available compounds.