Synthetic studies on Sch 202596, an antagonist of the galanin receptor subtype GalR1: an efficient synthesis of (±)-geodin, the spirocoumaranone part of Sch 202596

Katoh, Tadashi; Ohmori, Osamu; Iwasaki, Kengo; Inoue, Munenori

doi:10.1016/s0040-4020(01)01250-9

Cited by 45 publications

(30 citation statements)

References 36 publications

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“…Compound 2 was obtained as a yellow solid, and 3 was as a white solid, respectively. The UV and 1 H NMR spectral data of 2 were good agreement with those of dihydrogeodin [4]. Therefore 2 was identified as dihydrogeodin.…”

Section: Isolation and Identification Of (؉)-Geodin (1) Dihydrogeodisupporting

confidence: 54%

“…Further investigation revealed that mycelium extract of producing strain contained large quantities of dihydrogeodin (2), a biosynthetic precursor of (ϩ)-geodin. Oxidation of 2 with DDQ gave 54% yield of racemic geodin [4], which was identical to 1 with respect to 1 H NMR spectrum and chromatographic behavior on ODS HPLC. The activity of racemic 1 was comparable to that of the (ϩ)-isomer.…”

Section: Conversion Of Dihydrogeodin To Racemic Geodinmentioning

confidence: 80%

“…Analyses of various NMR spectral data deduced that 1 was (ϩ)-geodin. Finally, 1 was identified as (ϩ)-geodin by comparison with an authentic specimen [3,4]. Compound 2 was obtained as a yellow solid, and 3 was as a white solid, respectively.…”

Section: Isolation and Identification Of (؉)-Geodin (1) Dihydrogeodimentioning

confidence: 99%

“…After addition of 5% HCl, the mixture was extracted with ethyl acetate. The organic layer was dried over Na 2 SO 4 Methyl 5,7-Dichloro-4,6Ј-dimethoxy-6-methyl-3,4Ј-dioxospiro[benzofuran-2(3H),1Ј- [2,5]cyclohexadiene]-2Ј-carboxylate (5a) K 2 CO 3 (2 mg, 14 mmol) and methyliodide (3 ml, 32 mmol) were added to a solution of (Ϯ)-geodin (4.5 mg, 11.2 mmol) in DMF (0.2 ml), and stirred for 5 hours at room temperature. After addition of water, the mixture was extracted with ethyl acetate.…”

Section: Synthesis Of Geodin Analoguesmentioning

confidence: 99%

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Identification and Preliminary SAR Studies of (+)-Geodin as a Glucose Uptake Stimulator for Rat Adipocytes

et al. 2005

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(ϩ)-Geodin (1) was isolated from Penicillium glabrum AJ117540 with activity that stimulates glucose uptake by rat adipocytes. Unlike insulin it is active in the presence of wortmannin. Dihydrogeodin (2) and sulochrin (3) which are the precursors of (ϩ)-geodin biosynthesis were also isolated from the same fungus. Preliminary SAR studies of 1 showed some analogues had enhanced activity. Especially, the activities of racemic geodin and dibromo analogue (7a) were comparable to that of the natural product.

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Section: Isolation and Identification Of (؉)-Geodin (1) Dihydrogeodisupporting

confidence: 54%

Section: Conversion Of Dihydrogeodin To Racemic Geodinmentioning

confidence: 80%

Section: Isolation and Identification Of (؉)-Geodin (1) Dihydrogeodimentioning

confidence: 99%

Section: Synthesis Of Geodin Analoguesmentioning

confidence: 99%

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Identification and Preliminary SAR Studies of (+)-Geodin as a Glucose Uptake Stimulator for Rat Adipocytes

et al. 2005

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“…Similar reactivity was observed. 5 ) followed by benzylation gave 4 quantitatively, which was treated with NaClO 2 to afford carboxylic acid 5 quantitatively. Furthermore, similar conversion of 2 to 8, including the formation of a p-O-methoxymethyl ether instead of methylation, was also accomplished quantitatively.…”

Section: Resultsmentioning

confidence: 99%

Total synthesis of amidepsine B and revision of its absolute configuration

et al. 2009

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The total synthesis of (À)-amidepsine B, a potent diacylglycerol acyltransferase inhibitor, has been achieved. This synthetic study resulted in the revision of the previously assigned stereostructure of the natural amidepsine B and determined the absolute configuration. Keywords: absolute configuration; (À)-amidepsine B; total synthesis INTRODUCTION Amidepsines A-E were isolated from the culture broth of fungal strains FO-2942 and FO-5969 and found to be inhibitors of diacylglycerol acyltransferase (DGAT), 1-3 which is exclusively involved in triacylglycerol formation. Excessive accumulation of triacylglycerol can cause fatty liver, obesity and hypertriglyceridemia, which leads to serious diseases, such as atherosclerosis, diabetes and metabolic disorders. Therefore, DGAT inhibitors have the potential to become drugs. Spectroscopic analyses of the amidepsines elucidated depsipeptide structures consisting of three 4,6-dihydroxy-2-methylbenzoic acid derivatives and an amino acid (except for amidepsine D), as shown in Figure 1. The DGAT inhibitory activity of the amidepsines was tested by a cellular assay using Raji cells, and the results showed that amidepsine B (1) was the most potent inhibitor. Amidepsine B (1) was previously determined to be a mixture of stereoisomers at its single chiral center, the alanine alpha carbon. A 3:2 mixture of L-and D-alanines was revealed by acid hydrolysis followed by HPLC analyses using a chiral column (Amidepsines A and C were also reported as a 3:2 mixture of L-and D-amino acids 2 ). Herein, the total synthesis of amidepsine B and a revision of its absolute configuration will be described.

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