SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Spirodienones bearing the 1-azaspiro[4.5]decane ring system have been synthesized from N-methoxy-(4-halogenophenyl)amides by the intramolecular ipso attack of a nitrenium ion generated with [hydroxy(tosyloxy)iodo]benzene in trifluoroethanol.
The powerful methyl(trifluoromethyl)dioxirane (1b) was employed to achieve the direct oxyfunctionalization of 2,4-didehydroadamantane (5), spiro[cyclopropane-1,2'-adamantane] (9), spiro[2.5]octane (17), and bicyclo[6.1.0]nonane (19). The results are compared with those attained in the analogous oxidation of two alkylcyclopropanes, i.e., n-butylcyclopropane (11) and (3-methyl-butyl)-cyclopropane (14). The product distributions observed for 11 and 14 show that cyclopropyl activation of alpha-C-H bonds largely prevails when no tertiary C-H are present in the open chain in the tether; however, in the oxyfunctionalixation of 14 cyclopropyl activation competes only mildly with hydroxylation at the tertiary C-H. The application of dioxirane 1b to polycyclic alkanes possessing a sufficiently rigid framework (such as 5 and 9) demonstrates the relevance of relative orientation of the cyclopropane moiety with respect to the proximal C-H undergoing oxidation. At one extreme, as observed in the oxidation of rigid spiro compound 9, even bridgehead tertiary C-H's become deactivated by the proximal cyclopropyl moiety laying in the unfavorable "eclipsed" (perpendicular) orientation; at the other end, a cyclopropane moiety constrained in a favorable "bisected" orientation (as for didehydroadamantane 5) can activate an "alpha" methylene CH2 to compete effectively with dioxirane O-insertion into tertiary C-H bonds. Comparison with literature reports describing similar oxidations by dimethyldioxirane (1a) demonstrate that methyl(trifluoromethyl)dioxirane (1b) presents similar selectivity and remarkably superior reactivity.
We successfully isolated a spiro imidazolidine-oxazolidine intermediate in the reaction of guanidinium ylide mediated aziridination using alpha-bromocinnamaldehyde. X-ray crystallographic analysis unambiguously revealed that the stereogenic centers of the spiro intermediate were in a trans configuration. The role of the spiro compound as an intermediate in the aziridination reaction was confirmed by observation of its smooth chemical conversion into aziridine products.
Palladium-catalyzed intramolecular cyclization of N-(N'-tert-butylformimidoyl)-6-[2-(2-iodophenyl)ethyl]-1,2,3,4-tetrahydropyridine (1a) and N-(N'-tert-butylformimidoyl)-6-[3-(2-iodophenyl)propyl]-1,2,3,4-tetrahydropyridine (1b) respectively results in formation of spiro compounds 1'-(N-tert-butylformimidoyl)-3',4'-dihydrospiro[indan-1,2'(1'H)-pyridine] (4a), 1'-(N-tert-butylformimidoyl)-1',6'-dihydrospiro[indan-1,2'(3'H)-pyridine] (5a), and 1'-(N-tert-butylformimidoyl)-5',6'-dihydrospiro[indan-1,2'(1'H)-pyridine] (6a) and 1'-(N-tert-butylformimidoyl)-3,3',4,4'-tetrahydrospiro[naphthalene-1(2H),2'(1'H)-pyridine] (4b), 1'-(N-tert-butylformimidoyl)-1',3,4,6'-tetrahydrospiro[naphthalene-1(2H),2'(3'H)-pyridine] (5b), and 1'-(N-tert-butylformimidoyl)-3,4,5',6'-tetrahydrospiro[naphthalene-1(2H),2'(1'H)-pyridine] (6b). The double-bond migration process can be controlled, and any of the three double-bond isomers can be prepared by employing proper ligands. A combination of BINAP and the amidine function was required to obtain the isomers 5a and 5b with the double bond in the homoallylic position relative to the aryl group. An electrospray ionization mass spectrometric study was conducted to support suggested reaction intermediates.
[reaction: see text] The formal synthesis of (+/-)-desmethylamino FR901483 (2) is described. Construction of the unique azatricyclic skeleton of 2 was accomplished by a sequence which involved (i) preparation of dienone 7 by an N-methoxy-N-acylnitrenium ion-induced spirocyclization, (ii) formation of 2-azabicyclo[3.3.1]nonane 5 by the 6-(pi-exo)-exo-trig radical cyclization of 1,7-enyne 6, and (iii) installation of the C-5 p-methoxybenzyl side chain by Lewis acid-mediated alkylation of silyl enol ether 18.
[structure: see text]. A stereocontrolled total synthesis of the polycyclic Stemona alkaloid, (-)-stemospironine (1) has been achieved. Key transformations include the use of a Staudinger reaction leading to the aza-Wittig ring closure of the perhydroazepine system. Formation of the vicinal pyrrolidine butyrolactone is described via the stereoselective intramolecular capture of an intermediate aziridinium salt.
A highly efficient, stereocontrolled synthesis of (+)-4, the common C(7-19) tricyclic spiroketal fragment of the lituarines A, B, and C (1-3), has been achieved. Highlights of the synthesis include a remarkably facile 6-endo cyclization to access the C(8-12) pyran ring and a kinetically controlled acid-catalyzed spiroketalization. [reaction: see text]
An efficient synthetic approach to the tricyclic core 8 of lateriflorone is described. Essential to the synthesis was the implementation of a biomimetic tandem Claisen/Diels-Alder reaction that produced the desired tricyclic scaffold as a single isomer. A rationalization of the excellent regio and stereoselectivity of this transformation is also proposed. [reaction: see text]
[structure: see text] Two novel alkaloids with an unprecedented fused-pentacyclic skeleton, daphmanidins C (1) and D (2), have been isolated from the leaves of Daphniphyllum teijsmanii, and the structures were elucidated on the basis of spectroscopic data. The relative stereochemistry of 1 and 2 was assigned by combination of NOESY correlations and a simulation analysis. Daphmanidin C (1) elevated activity of NGF biosynthesis.
A unified, stereocontrolled synthesis of the C(1-19) segments of the lituarines A-C (1-3) has been achieved, highlighted by application of an iterative chemo- and stereoselective trienoate functionalization protocol, a strategy that holds considerable promise for the diversity oriented synthesis of polyketides.
[reaction: see text] A stereo-controlled synthesis of the fully elaborated C26-C40 tricyclic [5,6,6]-bis-spiroacetal of spirastrellolide A containing the C28 chlorine substituent is reported, exploiting asymmetric Sharpless dihydroxylation and boron-mediated allylation methodology.
[reaction: see text] Quantum mechanical calculations demonstrate that the second step of a Claisen-Diels-Alder reaction cascade controls regioselectivity that gives advanced intermediates for the synthesis of gambogin and 1-O-methyllateriflorone.
[structure: see text] Studies on the synthesis of the spirocyclic cyclohexadienone ring system 2 of the schiarisanrin family of natural products 1 are described and were based on the Lewis acid-promoted C-alkylation of the corresponding phenolic precursor.
Chinese hamster V79 cells were exposed to spirogermanium (SG), and their mitotic activity, population growth, plating efficiency, viability (dye exclusion), and clonogenicity were assayed. Mitotic frequency of cultures in SG decreased initially with increasing drug concentration and later plateaued at varying levels depending on drug concentration. Cultures continuously exposed to SG showed drug concentration-dependent growth inhibition, with no effect at 0.1-0.2 micrograms/ml and increasing toxicity above 0.5 microgram/ml. Cytolysis was enhanced by the simultaneous presence of amphoterocin B and by exposing cells to SG at 42 degrees C. Hypoxia protected cells from drug-induced lysis. The loss of membrane-intact cells was inversely related with population density at the time of drug exposure. Short exposures (up to 5 hours) at 20 micrograms/ml showed that cell killing was primarily through reduction of dye-excluding cells within a matter of hours and secondarily through loss of proliferative capacity. Prolonged drug contact (24 hours) at lower concentrations (1-5 micrograms/ml) accentuated the effect on clonogenicity. These results suggest that for clinical potency, prolonged drug contact may be beneficial.
Spirogermanium, a heavy metal compound in which germanium has been substituted in an azaspirane ring structure, was studied in 39 patients with advanced malignant neoplasms. Thirty-one patients were considered evaluable for toxic effects of spirogermanium. Transient neurological symptoms occurred in 12 patients (39%), including dizziness or lightheadedness, marked fatigue, visual blurring, ataxia, paresthesia, and nausea. These symptoms could be reduced by infusing the drug over 2 hours rather than over 1 hour. Persistent neurotoxicity in the form of partial loss of taste or extreme weakness was observed in three patients. No evidence of hematologic, renal, or hepatic toxicity was observed. Antitumor activity of spirogermanium was not identified in this group of heavily pretreated patients. Spirogermanium had limited and acceptable toxicity in utilizing a dose of 120 mg/m2 infused over 2 hours, three times weekly.
Conformational analyses and a structural comparison of the four spiro compounds 3-bromo-1,9-diphenyl-4-p-tolyl-7-oxa-1,2,8-triazaspiro[4.4]nona-2,8-dien-6-one, (I), C(24)H(18)BrN(3)O(2), 3-bromo-4-(4-methoxyphenyl)-1,9-diphenyl-7-oxa-1,2,8-triazaspiro[4.4]nona-2,8-dien-6-one, (II), C(24)H(18)BrN(3)O(3), 3-bromo-4-(4-chlorophenyl)-1,7,9-triphenyl-1,2,7,8-tetraazaspiro[4.4]nona-2,8-dien-6-one, (III), C(29)H(20)BrClN(4)O, and 3-bromo-1,7,9-triphenyl-4-p-tolyl-1,2,7,8-tetraazaspiro[4.4]nona-2,8-dien-6-one, (IV), C(30)H(22.89)Br(1.11)N(4)O, are presented. The molecular structures are rather similar, which is as expected since the compounds are all products of concerted 1,3-dipolar attack on (Z)-4-arylidene oxazolone and pyrazolone derivatives. The observed conformations tend to favour extended pi conjugation of the benzene rings and other pi systems, as shown by a comparison of selected geometric parameters of the four structures.
Explore the source record for details and available documents.
Explore the source record for details and available documents.