An update on the synthesis and reactivity of spiro-fused β-lactams

Beta-Lactam ring-containing compounds play a pivotal role in drug design and synthetic chemistry. Spirocyclic beta-lactams, representing an important beta-lactam subclass, have recently attracted considerable interest with respect to new synthetic methodologies and pharmacological applications. The aim of this manuscript is to review the recent progress made in this field, covering publications disseminated between 2011 to 2018 concerning the synthesis and application of spirocyclic beta-lactams. In the first part, new approaches to the synthesis of spirocyclic beta-lactams, including Staudinger synthesis, cyclization and transformation reactions, will be presented. The reactivity and biological properties of spiro-beta-lactams will be described in the second and third part, respectively

Zero-automatic queues and product form

We introduce and study a new model: 0-automatic queues. Roughly, 0-automatic queues are characterized by a special buffering mechanism evolving like a random walk on some infinite group or monoid. The salient result is that all stable 0-automatic queues have a product form stationary distribution and a Poisson output process. When considering the two simplest and extremal cases of 0-automatic queues, we recover the simple M/M/1 queue, and Gelenbe's G-queue with positive and negative customers

Technology Diffusion, North-South Spillovers and Industrial Location

Relying on a model of economic geography, this paper discusses development opportunities arising from international trade and technology diffusion. We show that either import substitution or trade liberalization may trigger takeoff in the developing country, although these two policies work through different mechanisms. The industrialization process is also influenced by knowledge spillovers: strong international technology diffusion offers better prospects for the developing country to benefit from technological externalities provided abroad. Thus, one objective of the developing country should be to enhance its absorptive capacity in order to exploit these technological externalities. In this context, only import substitution trade policy seems to be successful in financing indigenous learning process. However, this result is strongly dependent on the effectiveness of budgetary resource allocation.

Synthesis and reactivity of 4-(trifluoromethyl)azetidin-2-ones

Because of the beneficial effect of a trifluoromethyl group on the biological properties of bioactive compounds on the one hand and the versatile synthetic potential of beta-lactams on the other hand, 4-CF3-beta-lactams comprises interesting entities for the preparation of a large variety of CF3-substituted nitrogen-containing target structures with promising biological characteristics. In this review, we present an overview of different building block approach-based routes toward the synthesis of 4-(trifluoromethyl)azetidin-2-ones and the application of the "beta-lactam synthon method" for the synthesis of a diverse set of (a)cyclic CF3-substituted molecules by means of ring-opening and ring-transformation reactions

Synthesis of 4-(trifluoromethyl)azetidin-2-one building blocks and their transformation into novel CF3-substituted amines and heterocyclic systems

In light of the versatile synthetic potential of β-lactams on the one hand and the beneficial impact of fluorine on biological properties on the other hand, β-lactams bearing a trifluoromethyl group comprise interesting entities for the construction of novel targets with promising bioactivities. In this PhD thesis, the preparation and deployment of 4-trifluoromethyl-β-lactams as new building blocks toward a diverse set of functionalized CF3-amines and CF3-azaheterocycles was investigated. In particular, 3-benzyloxy-4-trifluoromethyl-β-lactams were conveniently synthesized as a first new class of building blocks. The aptitude of these systems with respect to ring-opening reactions was explored to enable an entry to functionalized aminopropane systems by either direct reductive β-lactam ring opening or initial carbonyl removal to azetidine intermediates, followed by ring opening. In addition, hydrogenolysis of the benzylether fragment in 3-benzyloxy-4-trifluoromethyl-β-lactams resulted in the formation of 3-hydroxy-4-trifluoromethyl-β-lactams as a second class of new building blocks. The latter alcohols enabled the construction of CF3-containing ring-rearranged products, including aziridines through a ring-contraction protocol via 3-chloro-β-lactam intermediates and dioxan-2-ones via initial O-allylation. Furthermore, alcohol oxidation gave rise to 3-oxo-4-trifluoromethyl-β-lactams as a third class of new building blocks. Attempts to form and trap the corresponding 2,3-dioxoazetidin-4-yl anions unexpectedly resulted in ring opening through C3-C4 bond fission, culminating in 2-[(2,2-difluorovinyl)amino]-2-oxoacetate products. This peculiar mechanism was investigated in depth, both experimentally and computationally. Finally, an addition/elimination sequence applied to 3-oxo-4-trifluoromethyl-β-lactams afforded 3-methylene-4-trifluoromethyl-β-lactams as a fourth class of new building blocks, which were shown to be eligible substrates for Michael additions, electrophilic additions and cycloadditions en route to a variety of stereodefined mono- and spirocyclic 4-CF3-β-lactams

Fates of lignin and carbohydrates in Siberian soils

Permafrost-affected soils contain a huge reservoir of organic matter (OM) which, in the past, was largely persistent against microbial decomposition as consequence of cool and waterlogged conditions in the active layer, and freezing in the permafrost layer. Knowing the composition and degree of decomposition at molecular level of soil organic matter (SOM) is relevant to assess their vulnerability under impacts of climate change. This thesis investigated two major constituents of SOM, lignin and carbohydrates, across a west-east gradient in northern Siberia (longitudinal transect) and along a north-south gradient in western Siberia (latitudinal transect), aiming at identifying their fate once permafrost is thawing. The longitudinal transect included three continuous permafrost sites, from Cherskiy (CH) in north-eastern, Logata (LG) in north-central, and Tazovskiy (TZ) in north-western Siberia, which principally differ in active layer thickness and soil mineralogical properties. The latitudinal transect included all major biomes (tundra, taiga, forest steppe and steppe) from arctic to temperate ecosystems, which vary in mean annual temperature (MAT), mean annual precipitation (MAP), vegetation and soil properties. Lignin-derived phenols and neutral sugars within plant and soil samples at each horizon were analysed by CuO oxidation and trifluoroacetic acid (TFA) extraction methods respectively. Along the longitudinal transect, the stage of lignin degradation, appeared to increase from TZ to CH site. The stronger degradation of lignin and neutral sugars at TZ is supposed to be due to the higher MAT and larger active layer thickness, coinciding with better aeration and/or better mobilization of OM. In addition, the larger contents of Fe and Al (hydr)oxides likely additionally stabilized lignin-derived phenols associated with the mineral phase at these sites. With respect to the latitudinal transect, the stage of lignin degradation appeared to increase from tundra to forest steppe, then decrease to steppe. The increasing degree of lignin decomposition from tundra to forest steppe is likely due to decreasing soil moisture and increasing temperature which might favor the activity and assimilation of lignin-degarded microoragnisms, while drought and high pH are responsible for the restrained lignin decomposition in the steppe biome. The restrained lignin decomposition, in turn impairs the degradation of plant-derived carbohydrates because of a chemical linkage in form of lignocelluloses. It can be expected that increasing soil temperature and consequently increasing active layer thickness as the result of climate warming, which can cause two different soil hydrological scenarios, i.e., warm drier and warm wetter conditions will likely promote lignin and carbohydrate decomposition. This thesis thus contributes to a better understanding of the impact of permafrost thaw on OM stabilization in high latitude, and a magnitude in the realease of greenhouse gases into the atmosphere under global warming

How We Care: Provider Perspectives on Services for Vietnamese Elderly in Boston’s Dorchester Neighborhood

The need for culturally competent care for the elderly is of growing concern for Asian American and Pacific Islander (AAPI) communities and health providers. In 2012, a preliminary study was conducted to ascertain the perspectives of service providers about the cultural competency of services for elderly Vietnamese Americans in Boston, Massachusetts. The study includes interviews with key informants representing the five major community health centers (CHC) programs in Boston’s Vietnamese enclave in the Dorchester neighborhood. Secondary data collection from field observations and informal communications with other staff and elderly clients also inform the findings. While the study recognizes the value of existing services, critical needs remain unmet in terms of resource allocation, client tracking, bicultural staff training and recruitment, targeted developmental activities for Vietnamese aging populations, and clear programmatic evaluation measurements. The study highlights the need for further research on cultural competency models and best practices for aging immigrant minority populations in Boston like the Vietnamese in Dorchester

BIODIVERSITY OF YEASTS ISOLATED FROM CON DAO ISLAND – BA RIA VUNG TAU

During the study on yeast diversity from natural samples in Viet Nam, we have collected 38 samples of flowers, fruits, leaves, litter and soils in Con Dao Island and isolated 54 yeast strains. They were identified based on morphology observation and sequences of D1/D2 domain of 26S rDNA. The results showed that they belonged to 13 genera, 28 species, of which 15 strains were suspected as 13 new species. Thirty-nine strains were identified as Ascomycetes belonging 7 genera, 11 species, and the fifteen remaining strains belonged to Basidomycetes, 6 genera and 13 species. The results also showed that four Ascomycetous and nine Basidomycetous isolated were suspected to be new species. The results also showed that Candida was the genus with highest number isolates- 26 strains, and half of these were Candida rugosa. The most diverse species in this study was found in Cryptococcus genus with 7 species from 8 isolates only, and all of them were suspected to be new species. This study also proved that the samples had differences in yeast diversity and species composition among them. Therefore, Con Dao Island is multi potential to discover and publish new yeast species in Vietnam.