- Stereoselective synthesis of 1,3-disubstituted dihydroisoquinolines vial-phenylalanine-derived dihydroisoquinoline N-oxides
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The preparation of chiral pool-derived nitrone 3 and its use in the protecting-group free, stereoselective synthesis of a range of 1,3-disubstituted tetrahydroisoquinolines is described. Grignard reagent additions to nitrone 3 yielded trans-1,3-disubstituted N-hydroxytetrahydroisoquinolines 6 with good levels of selectivity, while 1,3-dipolar cycloadditions to this nitrone provided access to 3-(2-hydroxyalkyl)isoquinolines 12 as single diastereomers.
- Flores-Ferrándiz, Jesús,Carter, Nicholas,González-Soria, Maria José,Wasinska, Malgorzata,Gill, Daniel,Maciá, Beatriz,Caprio, Vittorio
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p. 6961 - 6968
(2018/10/17)
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- Oxazolidines as Intermediates in the Asymmetric Synthesis of 3-Substituted and 1,3-Disubstituted Tetrahydroisoquinolines
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A diastereoselective mercury(II)-promoted intramolecular cyclization of unsaturated aldehyde via an oxazolidine to prepare C-3-substituted tetrahydroisoquinoline is disclosed. The C-3 stereogenic center is subsequently exploited to create the C-1 stereocenter by coordination of the nucleophilic reagent to the oxygen atom of oxazolidine. Both cis- and trans-1,3-disubstituted tetrahydroisoquinolines can be readily prepared. In addition, when a cationic rhodium complex was used, intramolecular hydroamination was effected, thus avoiding mercury(II) salts and demercuration. The reaction is general and works well using aliphatic and aromatic aldehydes.
- Raghavan, Sadagopan,Senapati, Puspamitra
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p. 6201 - 6210
(2016/08/16)
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- Practical and cost-effective manufacturing route for the synthesis of a β-lactamase inhibitor
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Compound 1, a potent and irreversible inhibitor of β-lactamases, is in clinical trials with β-lactam antibiotics for the treatment of serious and antibiotic-resistant bacterial infections. A short, scalable, and cost-effective route for the production of this densely functionalized polycyclic molecule is described.
- Miller, Steven P.,Zhong, Yong-Li,Liu, Zhijian,Simeone, Michael,Yasuda, Nobuyoshi,Limanto, John,Chen, Zheng,Lynch, Joseph,Capodanno, Vincent
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supporting information
p. 174 - 177
(2014/01/23)
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- Anticancer activity of ruthenium(II) arene complexes bearing 1,2,3,4-tetrahydroisoquinoline amino alcohol ligands
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Ruthenium complexes offer potential reduced toxicity compared to current platinum anticancer drugs. 1,2,3,4-tetrahydrisoquinoline amino alcohol ligands were synthesised, characterised and coordinated to an organometallic Ru(II) centre. These complexes were evaluated for activity against the cancer cell lines MCF-7, A549 and MDA-MB-231 as well as for toxicity in the normal cell line MDBK. They were observed to be moderately active against only the MCF-7 cells with the best IC50 value of 34 μM for the cis-dia-stereomeric complex C4. They also displayed excellent selectivity by being relatively inactive against the normal MDBK cell line with SI values ranging from 2.3 to 7.4.
- Chelopo, Madichaba P.,Pawar, Sachin A.,Sokhela, Mxolisi K.,Govender, Thavendran,Kruger, Hendrik G.,Maguire, Glenn E. M.
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p. 407 - 414
(2013/10/01)
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- An organogel formed from a cyclic β-aminoalcohol
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A new organogelator with unique structural feature of a cyclic β-aminoalcohol is presented as the first example of gelation by aminoalcohol through hydrogen-bonding between hydroxy and amine.
- Kang, Chuanqing,Bian, Zheng,He, Yabing,Han, Fushe,Qiu, Xuepeng,Gao, Lianxun
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supporting information; scheme or table
p. 10746 - 10748
(2011/11/29)
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- Synthesis of (S)-3-aminoethyl-1,2,3,4-tetrahydroisoquinoline (TIQ-diamine) via the Mitsunobu protocol
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The synthesis of (S)-3-Aminoethyl-1, 2, 3, 4-tetrahydroisoquinoline (TIQ-diamine) was successfully achieved via the Mitsunobu protocol. The method from earlier reports utilizing aminolysis of commercially available TIQ-amino methyl ester, and reduction of
- Kawthekar, Rahul B.,Peters, Byron K.,Govender, Thavendran,Kruger, Hendrik G.,Maguire, Glenn E.M.
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p. 195 - 198
(2013/01/09)
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- Utilizing the intramolecular Fukuyama-Mitsunobu reaction for a flexible synthesis of novel heterocyclic scaffolds for peptidomimetic drug design
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We report the synthesis of the novel scaffolds pyrazino[1,2-b]isoquinoline and pyrrolo[1,2-a]pyrazine displaying the somatostatin pharmacophores. Both classes of compounds contain a pyrazine heterocycle, which can be prepared in a straightforward manner utilizing an intramolecular Fukuyama-Mitsunobu reaction. As both the families derive from amino acids, they can be accessed in high optical purity.
- Zapf, Christoph W.,Del Valle, Juan R.,Goodman, Murray
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p. 4033 - 4036
(2007/10/03)
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- Isoquinolines useful as analgesics
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PCT No. PCT/SE97/00315 Sec. 371 Date Oct. 6, 1997 Sec. 102(e) Date Oct. 6, 1997 PCT Filed Feb. 25, 1997 PCT Pub. No. WO97/31940 PCT Pub. Date Sep. 4, 1997The present invention is directed to compounds that act as analgesics and that have the structure of
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- Enantioselective deprotonation of 4-tert-butylcyclohexanone by conformationally constrained chiral lithium amide bases
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Conformationally rigid chiral lithium amides based on a tetrahydroisoquinoline motif have been prepared bearing a range of substituents at C1 and C3. These bases were tested in the asymmetric deprotonation reaction of 4-tert-butylcyclohexanone. Although t
- Aggarwal, Varinder K.,Humphries, Paul S.,Fenwick, Ashley
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p. 2883 - 2889
(2007/10/03)
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- 3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N- methyltransferase versus the α2-adrenoceptor(1a)
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3-Hydroxymethyl-1,2,3,4-tetrahydroisoquinoline (4) is a more selective inhibitor (PNMT K(i) = 1.1 μM, α2 K(i) = 6.6 μM, selectivity (α2 K(i)/PNMT K(i)) = 6.0) of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), with respec
- Grunewald, Gary L.,Dahanukar, Vilas H.,Teoh, Bee,Criscione, Kevin R.
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p. 1982 - 1990
(2007/10/03)
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- Preparation and diastereoselective birch reduction-alkylation of chiral 3,4-dihydro-l (2h)-isoquinolinones. Enantiospecific syntheses and opioid receptor affinities of several hydro-2,3dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta[l,2-c]pyridine-9-ols
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Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2H)-isoquinolinones 6,10, and 15 from (1R,2S)-ephedrine, (1R,2R)-pseudoephedrine, and L-phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p-benzyloxybenzyl bromide, and p-methoxybenzyl bromide to give 7a-7e, lia, and 11b with diastereoselectivities > 20:1. Birch reduction-methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert-butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22. Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett. 1995, 36, 4551-4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (-)-26 and (+)-28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c. Ki values for the inhibition of binding to the μ-,δ-, and κ-opioid receptors by (-)-26, (+)-26, (+)-28, (-)-28, and (+)-32 are reported.
- Schultz, Arthur G.,Guzi, Timothy J.,Larsson, Erika,Rahm, Rainer,Thakkar, Kshitij,Bidlack, Jean M.
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p. 7795 - 7804
(2007/10/03)
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- Synthesis and biological activities of a novel class of azole-containing antifungal agents
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A series of novel 1,2,3,4-tetrahydroisoquinoline derived azoles has been designed and synthesized as antifungal agents which might function as inhibitors of cytochrome P-450 dependent lanosterol 14α-demethylase. In vitro tests showed that some of these compounds, especially 5b and 6b, effectively inhibit the growth of several strains of yeasts as well as molds.
- Liu, Lee Tai,Lin, Ya-Chuan,Wang, Chia-Lin J.,Lin, Mei-Shey,Yen, Su-Chen,Chen, Hsiao-Jen
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p. 1335 - 1338
(2007/10/03)
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- A Highly Effective One-Pot Bicycloannulation Methodology for the Synthesis of Berban and Yohimban Systems Based on Organotin-Mediated Three-Component Coupling (N-Acylative Pentadienylation of C=N Bonds)
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A highly effective bicycloannulation methodology for the synthesis of berban and yohimban alkaloid systems is described.Three-component coupling reactions of 2,4-pentadienyltin reagents with C=N bonds and α,β-unsaturated acyl chlorides furnish bicycloannulated products in a one-pot operation.For example, the reactions of 2,4-pentadienyltributyltin(1) with isoquinoline derivatives activated by acryloyl chloride afford the tetracyclic (+/-)-allo-berban systems stereoselectively.Similarly, the reaction of 1 with 3,4-dihydro-β-carboline (11) gives the pentacyclic (+/-)-allo-yohimban system.The reaction is not affected by the stereochemistry of the 2,4-pentadienyltin reagent.A new substituted 2,4-pentadienyltin reagent, 3-(hydroxymethyl)-2,4-pentadienyltrimethyltin (19), is prepared via 3-(hydroxymethyl)pentadienyl dianion.The three-component coupling reaction of 19 with 11 and acryloyl chloride affords the (+/-)-allo-16-(hydroxymethyl)yohimban system, from which (+/-)nitraraine is readily synthesized.In addition, 1,3-asymmetric induction leads to the high diastereoselectivity realized in bicycloannulation (up to 94percent de) when (S)-3--3,4-dihydroisoquinoline (27), which is readily derived from L-phenylalanine, is used in the three-component coupling reaction.
- Yamaguchi, Ryohei,Hamasaki, Takashi,Sasaki, Tohru,Ohta, Tetsuo,Utimoto, Kiitiro,et al.
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p. 1136 - 1143
(2007/10/02)
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- Enantioselective catalytic borane reductions of aromatic ketones: Syntheses and application of two chiral β-amino alcohols from (S)-porretine
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The in situ formed chiral oxazaborolidine catalysts from two optically active β-amino alcohols (S)-1 and (S)-2 from benzyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (S)-3 have been used successfully in the enantioselective catalytic homogenous bora
- Stingl,Martens,Wallbaum
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p. 223 - 226
(2007/10/02)
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- Isoquinoline derivatives and pharmaceutical compositions containing them
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Isoquinoline derivatives of the formula: wherein R represents alkyl of 1 through 10 carbon atoms, which are new compounds, possess pharmacological properties and are particularly active as anti-inflammatory, analgesic and antipyretic agents.
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