Diastereoselective intramolecular nitroaldol entry to lycoricidine alkaloids

McNulty, James; Mo, Ruowei

doi:10.1039/a800097b

Cited by 46 publications

(26 citation statements)

References 12 publications

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“…A short report on the synthesis of an advanced intermediate toward lycoricidine based on the construction of the C-ring using a Diels-Alder approach and subsequent functionalization of the cyclohexene ring has been proposed by Mehta [154]. 5,5-Dimethoxy-1,2,3,4-tetrachlorocyclopentadiene 173 was reacted with dimethoxystyrene 174 to provide the endo adduct in 84% yield.…”

Section: Iii-3-1) Formation Of the 10a-10b Bondmentioning

confidence: 99%

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Chemistry and Synthesis of Highly Oxygenated Alkaloids from Amaryllidaceae: Lycoricidine, Narciclasine, Pancratistatin and Analogs

Chapleur¹,

Chrétien²,

Ahmed³

et al. 2006

COS

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Plants of the genus Amaryllidaceae produce a number of alkaloids and other non-basic related molecules, some of them showing antitumor activities. The low availability of these often-complex structures, coupled with their interesting biological properties, has stimulated a long-standing interest in the chemistry community. Total syntheses of challenging structures such as lycoricidine, narciclasine and pancratistatin, which are highly oxygenated tetracyclic systems comprising up to six contiguous chiral centers on ring C, have been accomplished. These well-known structures, more than thirty years for lycoricidine, continue to stimulate interest in synthetic work to provide enough synthetic material or analogs, and also are a model target to test or develop new synthetic methodologies. The synthetic studies around these complex phenanthridinones made use of the latest up-to-date synthetic methodologies and led to the development of novel methods of functionalization and carbon-carbon bond formation. The purpose of this review is to summarize recent total syntheses and synthetic approaches towards these three highly oxygenated members of this particular class of alkaloids over the last twenty years. The review is arranged according to the different strategies used for the construction of the benzophenanthridinone ring system.

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Section: Iii-3-1) Formation Of the 10a-10b Bondmentioning

confidence: 99%

“…This compound was less potent than pancratistatin but was selective for some cell lines. The monohydroxylated compound 271, which was synthesized using the nitroaldol approach [154], showed almost no activity. The conclusion draw from theses studies is the importance of C-2 and C-3, and C-4 hydroxyl groups.…”

Section: Iii-4) Synthetic Analogsmentioning

confidence: 99%

Chemistry and Synthesis of Highly Oxygenated Alkaloids from Amaryllidaceae: Lycoricidine, Narciclasine, Pancratistatin and Analogs

Chapleur¹,

Chrétien²,

Ahmed³

et al. 2006

COS

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“…Basic alumina (activity I) promoted 6-exo-trig intramolecular nitroaldol reaction cyclization in a highly diastereoselective manner, during the synthesis of lycoricidine alkaloid analogs 62 [57]. As reported in the Scheme 19, the nitroaldehyde 60, easily prepared in two steps from the Michael addition of 59 to 58, is prone to give an internal nitroaldol reaction, under Al 2 O 3 catalysis, that allows a diatereomeric mixture of cyclic nitroalkanols in which the needed diateromer 61a is strongly prevalent (61a/61b = 95:5).…”

Section: Other Synthesismentioning

confidence: 99%

Synthetic Applications of Nitroalkanes Promoted by Solid Catalysis: Recent Results

Ballini

Palmieri

2006

COC

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Solid catalysis is crucial to chemical technology. Innumerable chemical reactions are facilitated by this catalytic system and, in this context, nitroalkanes have been demonstrated a great reactivity under solid catalysis, especially in the formation of new carbon-carbon single bond. In fact, aliphatic nitrocompounds are a valuable source of stabilized carbanions since the high electron-withdrawing power of the nitro group provides an outstanding enhancement of the hydrogen acidity at the alpha-position (cf. pK(a) MeNO2 = 10). Nitronate anions, that can be generated from nitroalkanes, using a wide range of bases, act as carbon nucleophiles with common electrophiles such as aldehydes (Nitroaldol-Henry-reaction), and electron-poor alkenes (Michael reaction), leading to carbon-carbon bond formation. In the last few decades several solid catalyses have been efficiently proposed for the employment of the nitroalkanes in the latter reactions. Very often the use of nitroalkanes, combined with solid catalysis, offers the opportunity to perform the reactions more efficiently, with enhanced chemoselectivity, high purity, improved yields and without the use of any solvent

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“…Although mitochondria of cancer cells were elucidated as 810 the site of action(McLachlan et al, 2005), the operable active tar-811 get for these compounds still remains elusive. Nonetheless, struc-812 tural details of the apoptosis-initiating pharmacophore have been 813 revealed through several structure-activity relationship (SAR) 814 refinement studies(McNulty and Mo, 1998;McNulty et al, 2001 McNulty et al, , 815 2005 Hudlicky et al, 2002; Ingrassia et al, 2009; Pettit et al, 816 2001 Pettit et al, 816 , 2006Rinner et al, 2004aRinner et al, , 2004b. These may be summa-817 rized as follows: (i) an intact phenanthridone nucleus is essential 818 as truncated analogues were significantly less active(Hudlicky 819 et al, 2002;McNulty et al, 2008); (ii) in relation to ring-A modifi-820 cation effects, it was shown that the methylenedioxyphenyl 821 moiety was necessary as structures incorporating other functional-822 ities, such as methoxyl or b-carboline, were on average over 100-823 fold less active in a number of cell lines compared to the parent 824 pancratistatin(Rinner et al, 2004a,b).…”

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confidence: 99%