New routes to functionalised pyridines

A novel method of preparing substituted pyridines has been developed. This method uses readily available [3-ketoesters and amidrazone as starting materials. The pyridines obtained do not require purification and different substitution patterns, not available by known methods, can be obtained. The formation of 1,2,3-tricarbonyl compounds was achieved by oxidation of the alcohol precursors, following two different methods. a-Chloro-ct-acetoxy-f3-dicarbonyls were prepared in excellent yields and were shown to react as tricarbonyl equivalents in the formation of 1,2,4-triazines. Regioselective condensation reactions were observed between different amidrazones with tricarbonyl and tricarbonyl equivalents to produce a series of novel 1,2,4-triazines in good yields with no contamination by any regioisomer. When 1,2,4-triazines were obtained from a-chloro-a-acetoxy-P-dicarbonyls, 2.5 equivalents of amidrazone were required. However, decomposition of a-chloro-a-acetoxy-P-dicarbonyls prior to reaction with 1 equivalent of amidrazone yielded the 1,2,4-triazines in good yields. These 1,2,4-triazines underwent aza Diels-Alder cycloaddition reactions with 2,5- norbornadiene to give a series of novel 2,3,6-trisubstituted pyridines. The pyridines bearing electron withdrawing groups as substituents could also be obtained in a 'one- pot' reaction from their corresponding tricarbonyls or tricarbonyl derivatives. The 1,2,4- triazines bearing electron donating groups could be converted to their corresponding pyridines either by changing the reaction conditions or, when possible, by conversion of the electron donating group into a more electron withdrawing substituent by oxidation (e.g. sulphoxide substituent). Pyridines bearing a sulphoxide substituent undergo nucleophilic substitutions, giving great scope to introduce different functionality in the C-6 of the pyridines.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Changing environments during the Middle-Upper Palaeolithic transition in the eastern Cantabrian Region (Spain): direct evidence from stable isotope studies on ungulate bones

Environmental change has been proposed as a factor that contributed to the extinction of the Neanderthals in Europe during MIS3. Currently, the different local environmental conditions experienced at the time when Anatomically Modern Humans (AMH) met Neanderthals are not well known. In the Western Pyrenees, particularly, in the eastern end of the Cantabrian coast of the Iberian Peninsula, extensive evidence of Neanderthal and subsequent AMH activity exists, making it an ideal area in which to explore the palaeoenvironments experienced and resources exploited by both human species during the Middle to Upper Palaeolithic transition. Red deer and horse were analysed using bone collagen stable isotope analysis to reconstruct environmental conditions across the transition. A shift in the ecological niche of horses after the Mousterian demonstrates a change in environment, towards more open vegetation, linked to wider climatic change. In the Mousterian, Aurignacian and Gravettian, high inter-individual nitrogen ranges were observed in both herbivores. This could indicate that these individuals were procured from areas isotopically different in nitrogen. Differences in sulphur values between sites suggest some variability in the hunting locations exploited, reflecting the human use of different parts of the landscape. An alternative and complementary explanation proposed is that there were climatic fluctuations within the time of formation of these archaeological levels, as observed in pollen, marine and ice cores.This research was funded by the European Commission through a Marie Curie Career Integration Grant (FP7- PEOPLE-2012-CIG-322112), by the Spanish Ministry of Economy and Competitiveness (HAR2012-33956 and Ramon y Cajal-2011-00695), the University of Cantabria and Campus International to ABMA. Radiocarbon dating at ORAU was funded by MINECO-HAR2012-33956 project. J.J was supported initially by the FP7- PEOPLE-2012-CIG-322112 and later by a Marie Curie Individual Fellowship (H2020-MSCA-IF-2014-656122). Laboratory work, associated research expenses and isotopic analysis were kindly funded by the Max Planck Society to M.R

The human remains from Axlor (Dima, Biscay, northern Iberian Peninsula)

OBJECTIVES We provide the description and comparative analysis of all the human fossil remains found at Axlor during the excavations carried out by J. M. de Barandiarán from 1967 to 1974: a cranial vault fragment and eight teeth, five of which likely belonged to the same individual, although two are currently lost. Our goal is to describe in detail all these human remains and discuss both their taxonomic attribution and their stratigraphic context. MATERIALS AND METHODS We describe external and internal anatomy, and use classic and geometric morphometrics. The teeth from Axlor are compared to Neandertals, Upper Paleolithic, and recent modern humans. RESULTS Three teeth (a left dm2, a left di1, and a right I1) and the parietal fragment show morphological features consistent with a Neandertal classification, and were found in an undisturbed Mousterian context. The remaining three teeth (plus the two lost ones), initially classified as Neandertals, show morphological features and a general size that are more compatible with their classification as modern humans. DISCUSSION The combined anatomical and stratigraphic study suggest that the remains of two different adult Neandertals have been recovered during the old excavations performed by Barandiarán: a left parietal fragment (Level VIII) and a right I1 (Level V). Additionally, two different Neandertal children lost deciduous teeth during the formations of levels V (left di1) and IV (right dm2). In addition, a modern human individual is represented by five remains (two currently lost) from a complex stratigraphic setting. Some of the morphological features of these remains suggest that they may represent one of the scarce examples of Upper Paleolithic modern human remains in the northern Iberian Peninsula, which should be confirmed by direct dating