Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment

Antascomicin B is a macrolide isolated from a strain of Micromonospora. It possesses structural similarities to FK506 and rapamycin and exhibits potent binding ability to FKBP12. Recent reports suggest that small molecule ligands of FKBP12 possess potent neuroprotective and neurodegenerative properties in mouse models of Parkinson\u27s disease. Our approach to the C1-21 fragment of antascomicin B involves an asymmetric amino-Claisen rearrangement originally developed by Tsunoda et al.35 report the scalability of the preparation and rearrangement of an allylic amide possessing a silyloxy group at the terminal position of the alkene. The Tsunoda-Claisen rearrangement uses inexpensive (S)-α-methylbenzylamine as the chiral auxiliary. The allylic amide underwent rearrangement to establish the C14 and C15 stereocenters in high yield and good diastereoselectivity. We found a surprisingly high yielding acid mediated lactonization that was employed to cleave the α-methylbenzyl amide. Details of these studies and further elaboration of the lactone are discussed. We also describe the progress toward the synthesis of the C1-21 fragment of the natural product

Inclusive Fundraising: Strategies to Qualify, Cultivate, Solicit, and Steward Alumnx of Color

Support from alumnx of color is increasingly important to universities due to loftier capital campaigns goal, and ever-increasing university tuition. Analyzing literature on giving patterns of multiple communities of color themes emerge on why alumnx of color do not give back to their alma maters. The issues of alumnx invisibility, trust and tangibility, and the importance of community are central among communities of color and what often inform their desire to donate. When these areas of focus are given the proper attention, universities can change how alumnx of color view the university and increase the significant gift potential of alumnx of color. Note: The use of alumnx instead of alumna/ae is intentional to be inclusive of all on individuals on the gender spectrum

Static large deviations for a reaction-diffusion model

We consider the superposition of a symmetric simple exclusion dynamics, speeded-up in time, with a spin-flip dynamics in a one-dimensional interval with periodic boundary conditions. We prove the large deviations principle for the empirical measure under the stationary state. We deduce from this result that the stationary state is concentrated on the stationary solutions of the hydrodynamic equation which are stable.Comment: 44 page

Occult macular dystrophy in an Italian family carrying a mutation in the RP1L1 gene.

Occult macular dystrophy (OMD) is an inherited macular disease characterized by progressive visual decline with the absence of visible retinal abnormalities. Typical alterations of the retinal structure are detectable by spectral domain optical coherence tomography (SD\u2011OCT). Mutations in the RP1L1 gene have been identified to be responsible for the disease in Asian subjects. The present study assessed the role of mutations in the RP1L1 gene in an Italian family with OMD. One patient with OMD and five related subjects (two male offspring affected by progressive visual decline and three asymptomatic siblings of the patient) were subjected to complete ophthalmological examination. SD\u2011OCT was also performed. All subjects were screened for OMD\u2011associated genetic mutations in the RP1L1 gene. The OMD patient and the two symptomatic offspring presented with a reduced best\u2011corrected visual acuity. Although no fundus abnormalities were observed, SD\u2011OCT examination showed that the external limiting membrane and the inner segment/outer segment band were not clearly identifiable and a focal disruption of the photoreceptor layer was present. The degree of photoreceptor alterations was correlated with the severity of visual impairment. Clinical and tomographic results in the three asymptomatic relatives were normal. A p.Arg45Trp mutation in the RP1L1 gene was identified in the OMD patient, in the two symptomatic offspring and also in two of the asymptomatic siblings of the patient. The identification of RP1L1 mutations in subjects with OMD may improve the accuracy of diagnosis of this rare condition and may aid in enhancing the efficacy of genetic counseling