Stereochemical effects in some acronycine derivatives

Mikros, Emmanuel; Mitaku, Sofia; Skaltsounis, Alexios‐Léandros; Libot, Francine; Tillequin, François; Koch, Michel

doi:10.1002/(sici)1097-458x(199907)37:7<498::aid-mrc490>3.0.co;2-p

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…However, the trans pseudo-diequatorial or the cis configuration is compatible with this coupling constant. The clear NOE correlation (Figure ) between H-2 and both methyls of the pyran ring and of H-1 with one of the methyls are in complete agreement with the cis configuration . Finally, computational conformation analysis was performed using molecular mechanics calculations, and these conclusions were in good agreement with the above experimental results.…”

supporting

confidence: 75%

Koniamborine, the First Pyrano[3,2-b]indole Alkaloid and Other Secondary Metabolites from Boronella koniambiensis

et al. 2005

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Two new alkaloids, (-)-cis-1,2-dihydroxy-1,2-dihydromedicosmine (3) and koniamborine (4), have been isolated from Boronella koniambiensis aerial parts. Their structures have been established from NMR and mass data. Koniamborine is a novel type of alkaloid, which derives from the pyrano[3,2-b]indole basic skeleton, described for the first time from nature. 6-Methoxy-1-methylisatin, also present in the plant material, can be considered biogenetically as a degradation product of the fused pyrone ring of 4.

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supporting

confidence: 75%

Koniamborine, the First Pyrano[3,2-b]indole Alkaloid and Other Secondary Metabolites from Boronella koniambiensis

et al. 2005

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“…Phase-sensitive NOESY experiments performed on O,N-dimethyl derivatives permitted to ascribe unambiguously angular structures to compounds 4 and 15, obtained from the major cyclization product 9 and 10, and linear structures to minor derivatives 11 and 12. 14 The (()-cis-diol 16 (Scheme 2) was conveniently obtained by catalytic osmium tetroxide oxidation of 4 using N-methylmorpholine N-oxide to regenerate the oxidizing agent. 15 Treatment of diol 16 with excess acetic Scheme 1.…”

Section: Chemistrymentioning

confidence: 99%

“…5-Hydroxy-1,1,13-trimethyl-2-methylene-1,2-dihydrobenzo [b]furo[3,2-h]acridin-6(13H)-one (14). Compound 14 was prepared from 10 under conditions similar with those described for the preparation of 13 from 10 (0.175 g, 0.5 mmol) using dry N,N-dimethylformamide (10 mL), sodium hydride (0.025 g of 50% oil dispersion, 0.5 mmol) and dimethyl sulfate (0.15 mL, 1.6 mmol.…”

Section: -Hydroxy-11-dimethyl-2-methylene-12-dihydrobenzo[b]furo[32-h...mentioning

confidence: 99%

“…In a similar way, 10 was converted into the corresponding N -methyl derivative 14 and O , N -dimethyl derivative 15 . Phase-sensitive NOESY experiments performed on O , N -dimethyl derivatives permitted to ascribe unambiguously angular structures to compounds 4 and 15 , obtained from the major cyclization product 9 and 10 , and linear structures to minor derivatives 11 and 12 1 Synthesis of 6-Methoxy-3,3,14-trimethyl- 3,14-dihydro-7 H -benzo[ b ]pyrano[3,2- h ]acridin-7-one a a Reagents and conditions: (i) refluxing heptan-1-ol, p -toluenesulfonic acid, 48 h; (ii) anhyd K 2 CO 3 and KI in dry DMF under argon, 24 h at 65 °C; (iii) heating 3 h at 130 °C; (iv) NaH (2.5 equiv) and (CH 3 ) 2 SO 4 (6 equiv) in dry DMF.

2 Compounds 7 , 8 , and 10 − 15 …”

Section: Chemistrymentioning

confidence: 99%

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Synthesis and Cytotoxic and Antitumor Activity of Benzo[b]pyrano[3,2-h]acridin-7-one Analogues of Acronycine

et al. 2000

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Benzo¿băcronycine (6-methoxy-3,3,14-trimethyl-3, 14-dihydro-7H-benzo¿bpyrano¿3,2-hăcridin-7-one, 4), an acronycine analogue with an additional aromatic ring linearly fused on the natural alkaloid basic skeleton, was synthesized in three steps, starting from 3-amino-2-naphthalenecarboxylic acid (5). Eight 1, 2-dihydroxy-1,2-dihydrobenzo¿băcronycine esters and diesters (17-24) were obtained by catalytic osmic oxidation, followed by acylation. All these compounds were significantly more cytotoxic than acronycine, when tested against L1210 leukemia cells in vitro. The potency of the cyclic carbonate 24 was in the range of the most active drugs currently used in cancer chemotherapy. Two selected diesters (17 and 24) were evaluated in vivo against P388 leukemia and colon 38 adenocarcinoma implanted in mice. Both compounds were markedly active at doses 16-fold lower than the dose of acronycine itself. Against colon 38 adenocarcinoma, compounds 17 and 24 were highly efficient, inhibiting tumor growth by more than 80%. Diacetate 17 was the most active, inhibiting tumor growth by 96% at 6.25 mg/kg, with two of seven mice being tumor-free on day 43.

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“…Since the pyran D ring appears to play a crucial role in the biological activity of this group of compounds, NMR spectroscopic studies were undertaken to probe the stereochemistry and conformation of this ring in the natural and synthetic compounds 226-242. 96 The publication gives comprehensive tabulations of 1 H and 13 C NMR data, as well as full details of the NOESY and coupling constant analyses on which the conformational analysis was based. Conformational analysis by molecular mechanics was also used to corroborate the spectroscopic results.…”

mentioning

confidence: 99%