Eocene intra-plate shortening responsible for the rise of a faunal pathway in the northeastern Caribbean realm

Intriguing latest Eocene land-faunal dispersals between South America and the Greater Antilles (northern Caribbean) has inspired the hypothesis of the GAARlandia (Greater Antilles Aves Ridge) land bridge. This landbridge, however, should have crossed the Caribbean oceanic plate, and the geological evolution of its rise and demise, or its geodynamic forcing, remain unknown. Here we present the results of a land-sea survey from the northeast Caribbean plate, combined with chronostratigraphic data, revealing a regional episode of mid to late Eocene, trench-normal, E-W shortening and crustal thickening by ∼25%. This shortening led to a regional late Eocene–early Oligocene hiatus in the sedimentary record revealing the location of an emerged land (the Greater Antilles-Northern Lesser Antilles, or GrANoLA, landmass), consistent with the GAARlandia hypothesis. Subsequent submergence is explained by combined trench-parallel extension and thermal relaxation following a shift of arc magmatism, expressed by a regional early Miocene transgression. We tentatively link the NE Caribbean intra-plate shortening to a well-known absolute and relative North American and Caribbean plate motion change, which may provide focus for the search of the remaining connection between ‘GrANoLA’ land and South America, through the Aves Ridge or Lesser Antilles island arc. Our study highlights the how regional geodynamic evolution may have driven paleogeographic change that is still reflected in current biology

Expanding Stereochemical and Skeletal Diversity Using Petasis Reactions and 1,3-Dipolar Cycloadditions

A short and modular synthetic pathway using intramolecular 1,3-dipolar cycloaddition reactions and yielding functionalized isoxazoles, isoxazolines, and isoxazolidines is described. The change in shape of previous compounds and those in this study is quantified and compared using principal moment-of-inertia shape analysis.Chemistry and Chemical Biolog

Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

Behavior of hydrazonoyl chlorides towards the C=N double bond of Delta(2)-pyrazolines. A study on 2-(4-nitrophenyl)-2,3,3a,4,5,6-hexahydro-6-oxofuro[3,4-c]pyrazole

The reaction between title compound (3) and hydrazonoyl chlorides (4) was performed in the presence of triethylamine or silver salts. The product output was quite different depending upon the basic agent and, besides the formation of the novel pyrazolo[4,5-b]furo[3,4-c]pyrazole skeleton, a new degradative behavior of the pyrazoline ring has been observed

MeOPEG-bounded azide cycloadditions to alkynyl dipolarophiles

The MeOPEG-supported azide 2 was reacted in the presence of a number of alkynyl dipolarophiles. The corresponding 1-MeOPEG-supported-1,2,3-triazoles were obtained in nearly quantitative yields. Acidic hydrolysis of the cycloadducts 5b and 6b caused the removal of the MeOPEG pendant giving 4-methoxycarbonyl-1,2,3-triazole 9 and 5-methoxycarbonyl-1,2,3-triazole 10, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved

Oxygenated monoterpenes as dipolarophiles for nitrilimine cycloadditions

A variety of naturally-occurring oxygenated monoterpenes, namely (S)-cis-verbenol, (1R)-(-)-myternol, (1S)-(-)-verbenone, (1R)-(-)-myternal, (S)-(-)-perillyl alcohol, and (S)-(-)-perillaldehyde have been submitted to nitrilimine cycloaddition. These processes were fully regio- and stereoselective for four dipolarophiles. In contrast, regioselective but non-stereoselective cycloadditions occurred in the case of two of the monoterpene derivatives. The configurations of the newly-formed stereocentres of the cycloadducts were assigned on the basis of NOE and NOESY experiments

SILVER CARBONATE PROMOTED REACTION OF HYDRAZONYL CHLORIDES WITH ALLYLIC ALCOHOLS

The title reaction affords two main kinds of products: (i) pyrazole derivatives due to cycloaddition of a nitrile imine intermediate to the ethylenic bond; (ii) open-chain carbonyl compounds due to the electrophilic attack of a nitrilium-like carbocation to the ethylenic bond. Mechanistic possibilities are discussed

NOVEL-APPROACH TO 1-ARYL-1H-4,1,2-BENZOXADIAZINES INVOLVING A SMILES REARRANGEMENT

Some representatives of the title ring system have been obtained from ortho-(aryloxy)phenylhydrazonyl chlorides through a pathway involving (i) nitrile imide formation, (ii) Smiles rearrangement and (iii) intramolecular nucleophilic addition

Intramolecular cycloadditions of N-alkenoyl aryl azides

Depending upon the reaction conditions, intramolecular cycloadditions of variously substituted N-alkenoyl aryl azides 4 give the [1,2,3]triazolobenzodiazepine 5, bridgehead aziridines 6 or imines 7. The dipolarophilic activity of the C=N double bond of the latter compounds is also exploited in the synthesis of [1,2,4]triazolobenzodiazepines 10 by means of nitrilimine cycloadditions

Nitrilimine cycloadditions to MeOPEG-bounded alkenyl dipolarophiles

Base treatment of hydrazonoyl chloride 2 with MeOPEG-supported acrylates 1 and acrylamides 5 gave the corresponding MeOPEG-supported 4,5-dihydropyrazoles 3 and 6. Basic hydrolysis of the cycloadducts caused the removal of the MeOPEG pendant giving 5-carboxy- or 5-aminocarbonyl- 4,5-dihydropyrazoles 7 and 8, respectively. Cycloaddition between 2 and enantiopure MeOPEG-supported acrylamide 10 gave a mixture of MeOPEG-supported cycloadducts 11 and 12 with low diastereoselectivity