Radical transformations of ENT-isocopalic diterpenes

Gîrbu Vladilena; Ungur Nikon; Kulciţki Veaceslav; Renaud Philippe

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2023-06-09 12:39

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GÎRBU, Vladilena, UNGUR, Nikon, KULCIŢKI, Veaceslav, RENAUD, Philippe. Radical transformations of ENT-isocopalic diterpenes. In: Achievements and perspectives of modern chemistry, 9-11 octombrie 2019, Chişinău. Chisinau, Republic of Moldova: Tipografia Academiei de Ştiinţe a Moldovei, 2019, p. 220. ISBN 978-9975-62-428-2.

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Achievements and perspectives of modern chemistry 2019

Conferința "International Conference "Achievements and perspectives of modern chemistry""
Chişinău, Moldova, 9-11 octombrie 2019

Radical transformations of ENT-isocopalic diterpenes

Pag. 220-220

Gîrbu Vladilena¹, Ungur Nikon¹, Kulciţki Veaceslav¹, Renaud Philippe²

¹ Institute of Chemistry,
² University of Bern

Disponibil în IBN: 11 noiembrie 2019

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Spongiane diterpenoids are natural compounds isolated form sponges, corals and marine mollusks. Most of them play a key role as physiological mediators and are of interest for potential applications as therapeutic agents. These diterpenoids possess biological properties including antifungal, anti-inflammatory, cytotoxic and anti-HIV activities [1, 2]. Methyl ent-isocopalate, the tricyclic diterpene of the spongian family is used as a good precursor in the total synthesis of natural compounds [3]. It was obtained in 61% overall yield, starting from sclareol, a commercially available and inexpensive compound. Carboazidation of methyl ent-isocopalate with ethyl iodoacetate and phenylsulfonyl azide under DTBHN initiation conditions resulted in the formation of azide 2 in 55% yield (Figure). The relative stereochemistry of azide 2 was determined based on NOESY NMR data.formulaFigure. Radical carboazidation of diterpenes. Reagents and conditions: a. ICH2CO2Et (2 equiv.), 3-PySO2N3 (3 equiv.), Bu6Sn2 (1.5 equiv.), DTBHN (0.03 equiv.), benzene, 10 h, delta; b. imidazole (4 equiv.), TBDMSCl (2 equiv.), DMF, r.t. overnight; c. ICH2CO2Et (2 equiv.), PhSO2N3 (3 equiv.), Bu6Sn2 (1.5 equiv.), DTBHN (0.03 equiv.), benzene, 10 h, delta; d. TBAF (3 equiv.), THF, r.t., overnight. e. H2, Pd/C, EtOAc, r.t., 48 h. The 12 a-hydroxy-ent-isocopal-13(16)-en-15-oic acid 3 was synthesized from isocopalic ester 1 according to the known procedure [4]. Then, compound 3 was transformed via the TBDS ether 4 into lactam 5 over 3 steps in a 63% total yield. The key step in this sequence was the carboazidation of the exomethylenic double bond, followed by reduction of the azide moiety, which triggered a spontaneous lactamization. The introduced heteroatomic functional groups represent new structural motifs integrated into the isocopalic framework and their effect on the biological properties is currently under investigation.

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