21622-08-2Relevant articles and documents
Assembly of the 1-azaspiro[5.5]undecane framework associated with perhydrohistrionicotoxin via electrocyclic ring-opening of a ring-fused gem-dichlorocyclopropane and trapping of the resulting π-allyl cation by a tethered, nitrogen-centered nucleophile
Banwell, Martin G.,Vogt, Florian,Wu, Angela W.
, p. 415 - 425 (2006)
The carbamate-tethered gem-dichlorocyclopropane 27 was prepared, as a mixture of epimers, in ten steps from commercially available β,γ-unsaturated nitrile 9. Upon treatment with silver acetate under a range of reaction conditions, compound 27 underwent electrocyclic ring opening to give the corresponding ?-allyl cation that was then trapped by the reaction solvent, chloride ion, and/or acetate ion, and so affording varying mixtures of the chlorocyclohexenes 28, 29, 30, and/or 31. Sequential treatment of the same substrate with LiHMDS (to generate the conjugate base of this carbamate) then silver tetrafluoroborate afforded the chlorocyclohexadiene 32 as the exclusive product of reaction. No spirocyclization product of the type 3 arising from trapping of the intermediate ?-allyl cation by the tethered carbamate was observed under any of the reaction conditions examined. In contrast, analogous treatment of the more rigid system 38 afforded compound 39 incorporating the 1-azaspiro[5.5]undecane framework associated with the potent neurotoxin perhydrohistrionicotoxin (2). CSIRO 2006.
(E)-3-(2,2-dibromospiro[2.4]heptan-1-yl)-propenenitrile
Banwell, Martin G.,Hockless, David C. R.,Wu, Angela W.
, p. 504 - 506 (1997)
The X-ray crystal structure of the title compound, C10H11Br2N, reveals that the three- and five-membered rings are fused to one another in a spiro fashion and that there is an E arrangement of substituents about the carbon-carbon double bond.
Synthesis of novel shikonin derivatives and pharmacological effects of cyclopropylacetylshikonin on melanoma cells
Durchschein, Christin,Bauer, Rudolf,Kretschmer, Nadine,Hufner, Antje,Rinner, Beate,Stallinger, Alexander,Deutsch, Alexander,Lohberger, Birgit
supporting information, (2018/11/23)
Despite much research in the last centuries, treatment of malignant melanoma is still challenging because of its mostly unnoticeable metastatic spreading and aggressive growth rate. Therefore, the discovery of novel drug leads is an important goal. In a previous study, we have isolated several shikonin derivatives from the roots of Onosma paniculata Bureau & Franchet (Boraginaceae) which evolved as promising anticancer candidates. β,β-Dimethylacrylshikonin (1) was the most cytotoxic derivative and exhibited strong tumor growth inhibitory activity, in particular, towards melanoma cells. In this study, we synthesized eighteen novel shikonin derivatives in order to obtain compounds which exhibit a higher cytotoxicity than 1. We investigated their cytotoxic potential against various melanoma cell lines and juvenile skin fibroblasts. The most active compound was (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl cyclopropylacetate (cyclopropylacetylshikonin) (6). It revealed significant stronger tumor growth inhibitory activity towards two melanoma cell lines derived from metastatic lesions (WM164 and MUG-Mel2). Further investigations have shown that 6 induced apoptosis caspase-dependently, increased the protein levels of cleaved PARP, and led to double-stranded DNA breaks as shown by phosphorylation of H2AX. Cell membrane damage and cell cycle arrest were not observed.
Isothiourea-mediated asymmetric functionalization of 3-alkenoic acids
Morrill, Louis C.,Smith, Samuel M.,Slawin, Alexandra M. Z.,Smith, Andrew D.
, p. 1640 - 1655 (2014/03/21)
Isothiourea HBTM-2.1 promotes the catalytic asymmetric α- functionalization of 3-alkenoic acids through formal [2 + 2] cycloadditions with N-tosyl aldimines and formal [4 + 2] cycloadditions with either 4-aryltrifluoromethyl enones or N-aryl-N-aroyl diazenes, providing useful synthetic building blocks in good yield and with excellent enantiocontrol (up to >99% ee). Stereodefined products are amenable to further synthetic elaboration through manipulation of the olefinic functionality.
Reaction of N-acetylimidazole with enamines
Cook, Gilbert,Waddle, Julie L.
, p. 6923 - 6925 (2007/10/03)
N-Acetylimidazole is a commonly used acylating reagent. When it is allowed to react with several typical enamines, amides are produced rather than the expected acylated enamines.
Preparation of allylic lithium reagents with the allylic system partly incorporated into carbocyclic rings
Screttas, Constantinos G.,Smonou, Ioulia C.
, p. 143 - 152 (2007/10/02)
A new method is described for preparation of allylic type organolithiums in which two of the allylic system carbons form part of carbocyclic ring.It involves cleavage of the readily accessible allylic sulfides 1-phenylthiomethylcycloalkanes by the naphthalenelithium in tetrahydrofuran.Carbonation of the reagents has given mixtures of cycloalken-1-yl acetic acids and 2-methylecycloalkane carboxylic acids, the distribution of which is strongly dependent on the ring size; thus the proportion of cycloalkenyl acetic acid, the endocyclic olefinic product, increases sharply on going from C5 to C8 ring derivatives and then considerably less sharply on going from C8 to C10 at which point the carbonation reaction has a high selectivity.It is concluded that the site of attack in the allylic anion by CO2 is determined by the thermochemical stability of the product(s).
LONG-ACTING CONTRACEPTIVE AGENTS: LEVONORGESTREL ESTERS OF UNSATURATED ACIDS
Wan, A. S. C.,Ngiam, T. L.,Leung, S. L.,Go, M. L.,Francisco, C. G.,et al.
, p. 339 - 348 (2007/10/02)
Esters of levonorgestrel (13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one) with a variety of unsaturated carboxylic acids have been synthesized for evaluation as potential long-acting, injectable contraceptive agents.
