Isoquinoline Unit Research Articles

Total Synthesis of Cortistatins A and J

This paper describes the details of our synthetic studies on the marine steroidal alkaloids cortistatins A and J. The key features of our strategy include (i) an efficient Knoevenagel/electrocyclic strategy to couple the diketone and the CD-ring fragment, (ii) a chemoselective radical cyclization to construct the oxabicyclo[3.2.1]octene B-ring system, (iii) a highly stereocontrolled installation of the isoquinoline unit, and (iv) a late-stage functionalization of the A-ring.

海洋生物からの医薬シーズの探索

In search of new pharmaceutically valuable substances from marine organisms, we have been engaged in chemical studies 1] structural elucidation; 2] asymmetric total synthesis; 3] elucidation of pharmacophore by analysis of structure–activity relationship; 4] action mechanism and search for target protein on the bioactive substances, which were isolated from marine invertebrates and marine microorganisms at Japanese coasts and Indonesian coral reefs on the guidance of new practical bioassay. a) Anti–angiogenic substance: selective growth–inhibitor against human umbilical vein endothelial cells (HUVECs) (e.g. cortistatin A: 9(10–19)–abeo–androstane–type steroidal alkaloid having isoquinoline unit) b) Hypoxia–selective growth inhibitor: growth inhibitor against tumor cells under hypoxic environment selectively (e.g. furospinosulin–1: furanosesterterpene) c) Anti–mycobacterial substances, which are effective to both active and non–replicating persistent (NRP) states of tuberculosis (e.g. halicyclamine A: macrocyclic alkaloid)

1-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-phenylisoquinoline

The mol­ecular conformation of the title compound, C20H17N3, is stabilized by an intramolecular C—H⋯N inter­action. The crystal structure shows inter­molecular C—H⋯π inter­actions. The dihedral angle between the isoquinoline unit and the phenyl ring is 11.42 (1)° whereas the isoquinoline unit and the pendent dimethyl pryrazole unit form a dihedral angle of 50.1 (4)°. Furthermore, the angle between the mean plane of the phenyl ring and the dimethyl pyrazole unit is 47.3 (6)°.

N-[3-(2-Methylphenyl)isoquinolin-1-yl]formamide

The title compound, C17H14N2O, crystallizes as a cis formamide isomer. The isoquinoline and benzene fragments are nearly perpendicular [dihedral angle = 81.79 (18)°], whereas the formamide group is virtually coplanar with the isoquinoline unit [dihedral angle = 1.66 (15)°]. Inter­molecular N—H⋯O hydrogen bonds link mol­ecules into a centrosymmetric dimer.

Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A

The highly stereoselective attachment of isoquinoline onto the steroidal framework of cortistatin A has been achieved. Our strategy features a Ce-mediated nucleophilic addition of an isoquinoline unit to the sterically congested ketone followed by formation of the phenyl thiocarbamate, and subsequent stereoselective radical reduction. The new method results in a formal total synthesis of cortistatin A.

Cortistatins J, K, L, Novel Abeo‐9(10—19)‐androstane‐Type Steroidal Alkaloids with Isoquinoline Unit, from Marine Sponge Corticium simplex

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Structure–activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids

Previously, bioassay-guided separation led us to isolate eleven novel steroidal alkaloids named cortistatins from the marine sponge Corticium simplex. These cortistatins were classified into three types based on the chemical structure of the side chain part, that is, isoquinoline, N-methyl piperidine or 3-methylpyridine units. From the structure–activity relationship study, the isoquinoline unit in the side chain was found to be crucial for the anti-angiogenic activity of cortistatins. Cortistatin A ( 1) showed cytostatic growth-inhibitory activity against human umbilical vein endothelial cells (HUVECs). Cortistatin A ( 1) also inhibited VEGF-induced migration of HUVECs and bFGF-induced tubular formation. Although cortistatin A ( 1) showed no effect on VEGF-induced phosphorylation of ERK1/2 and p38, which are one of the signaling pathways for migration and tubular formation, the phosphorylation of the unidentified 110 kDa protein in HUVECs was inhibited by the treatment with cortistatin A.

3-Ethyl 1-methyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate

In the mol­ecular structure of the title compound, C17H15NO4, the pyrrolo[2,1-a]isoquinoline unit is planar. The crystal structure is stabilized by weak intra- and inter­molecular C—H⋯O inter­actions, and also by π–π inter­actions with centroid–centroid distances of 3.5680–3.6683 Å.

Cortistatins J, K, L, novel abeo-9(10-19)-androstane-type steroidal alkaloids with isoquinoline unit, from marine sponge Corticium simplex

Three novel anti-angiogenic steroidal alkaloids, cortistatins J ( 1), K ( 2), L ( 3), have been isolated from the Indonesian marine sponge Corticium simplex. The chemical structures of cortistatins J ( 1), K ( 2), and L ( 3) were determined by 2D-NMR analysis to be unique abeo-9(10-19)-androstane-type steroidal alkaloids having isoquinoline unit instead of the side chain part, respectively. Cortistatin J ( 1) showed cytostatic anti-proliferative activity against human umbilical vein endothelial cells (HUVECs) at 8 nM, in which the selective index was 300–1000-fold in comparison with other cell lines.

Total synthesis of 8,9,11,12-tetramethoxy-2-methyl-1,2,3,4-tetrahydronaphtho[2,1-f]isoquinoline and 8,9,11-trimethoxy-2-methyl-1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolin-12-ol

We describe here the first total synthesis of two tetrasubstituted 1,2,3,4-tetrahydronaphtho[2,1f]isoquinolines (8,9,11,12-tetramethoxy-2-methyl-1,2,3,4-tetrahydronaphtho[2,1-f]isoquinoline and 8,9,11-trimethoxy-2-methyl-1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolin-12-ol). The key steps were the Bischler-Napieralski cyclization of ethyl (2-{2-[2-(3,4-dimethoxyphenyl)vinyl]4,5-dimethoxyphenyl}ethyl)methylcarbamates to form the isoquinoline units and photocyclization of the resulting 5-[2-(3,4-dimethoxyphenyl)vinyl]-7,8-dimethoxy-2-methyl-3,4dihydroisoquinolin-1(2H)-ones to 8,9,11,12-tetramethoxy-2-methyl-3,4-dihydronaphtho[2,1f]isoquinolin-1(2H)-ones.

Ancisheynine, a Novel Naphthylisoquinolinium Alkaloid from Ancistrocladus heyneanus.

A novel naphthylisoclumoline alkaloid, ancisheynine 1, was isolated from the aerial part of Ancistrocladus heyneanus Wallich ex J. Graham (Ancistrocladaceae). Ancisheynine 1 contained a previously undescribed N-2,C-8'-linkage between the isoquinoline and naphthalene units and its structure was established by spectroscopic methods. (C) 2003 Elsevier Ltd. All rights reserved.

First total syntheses of the 1,2,3,4-tetrahydronaphtho[2,1- f]isoquinolines annoretine and litebamine

We describe here the first total synthesis of the two natural 1,2,3,4-tetrahydronaphtho[2,1- f]isoquinolines, annoretine and litebamine, from [2-(2-styrylphenyl)ethyl]methylcarbamic acid ethyl esters. The key steps were the Bischler–Napieralski cyclization to form the isoquinoline unit and photocyclization of the resulting 2-methyl-5-styryl-3,4-dihydro-2 H-isoquinolin-1-ones to 2-methyl-3,4-dihydro-2 H-naphtho[2,1- f]isoquinolin-1-ones.

Electrochemical synthesis and characterization of a new conducting copolymer having amino isoquinoline units to influence redox characteristics

5-Aminoisoquinoline (AIQ), a bifunctional monomer, having an aniline type –NH 2 group and a –CN–C group in quinoline ring, was specifically electropolymerized utilizing the –NH 2 groups to leave the –CN–C groups in the ring intact in the resulted polymer. Electrochemical characteristics for the polymerization of mixture of aniline (ANI) and AIQ was investigated via cyclic voltammetry. Individual electrochemical homopolymerization studies for ANI and AIQ were also performed to deduce the changes in the electrochemical characteristics during polymerization with ANI and AIQ together. X-ray photoelectron spectroscopy (XPS) was employed to find the elemental composition and proportion of reduced units in the copolymer. The presence of –CN–C groups in the copolymer is evident from XPS and in situ spectroelectrochemical results. Double potential chronocoulometry was used to obtain the diffusion characteristics of the copolymer film modified electrode. Oxidation of hydroquinone was performed on the copolymer film modified electrode.

First total synthesis of the 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinoline annoretine

Here we describe the first total synthesis of the 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinoline (6) annoretine from N-carbethoxy-o-styrylphenylethylamines 2. The key steps were the Bischler–Napieralski reaction to form the isoquinoline unit and photocyclization of the resulting 5-styrylisoquinoline 3 to naphtoisoquinoline 4.

First total synthesis of 1,2,3,4-tetrahydronaphtho[2,1- f]isoquinolines

Here we describe the first total synthesis of 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines ( 7) from N-acyl-o-styrylphenylethylamines 3. It proceeds by the Bischler-Napieralski reaction to form the isoquinoline unit and photocyclization of the resulting 5-styrylisoquinolines 5.

ChemInform Abstract: Marine, Nitrogen‐Containing Heterocyclic Natural Products. Structures and Syntheses of Compounds Containing Quinoline and/or Isoquinoline Units

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