Flexible approach to stemona alkaloids : total syntheses of (-)-stemospironine and rhree new diastereoisomeric analogs /

Els extractes d'algunes plantes de la família Stemonaceae s'utilitzen als països asiàtics pel tractament de diferents malalties i per les seves propietats antiparasitàries. Aquests extractes contenen una sèrie d'alcaloides amb estructures relacionades que són responsables dels seus efectes terapèutics. Tots els alcaloides d'Stemona són compostos policíclics i la majoria presenten un nucli de pirrolo[1,2-a]azepina com a característica estructural més destacada. Molts d'ells incorporen una o més subestructures d'α-metil-γ-butirolactona unides al nucli azabicíclic. El nostre grup de recerca va dissenyar una estratègia en la que el nucli de pirroloazepina es genera al principi de la seqüència i els altres fragments específics s'integren posteriorment, per poder accedir a diferents alcaloides a partir d'un intermedi comú, generant diversitat molecular. El nucli azabicíclic característic es sintetitza mitjançant una reacció de cicloaddició 1,3-dipolar entre una nitrona quiral i una olefina electrodeficitària. En aquesta tesi, s'han sintetitzat stemospironina i tres nous anàlegs diastereoisomèrics, 116, 119 i 120. Així, la reacció d'spirolactonització de l'intermedi clau 62 es va fer mitjançant esterificació de l'alcohol terciari i posterior tractament bàsic del fosfonat 86, proporcionant la lactona 63. Després de la desprotecció de l'alcohol seguit d'oxidació, el corresponent aldehid es va tractar amb bromometilacrilat d'etil i zinc, per obtenir una mescla 1:1 de bislactones. Després de la hidrogenació dels dobles enllaços, cada bislactona es va convertir en la corresponent amina 116 o 120. Per altra banda, la reacció d'spirolactonització de 125 va proporcionar la lactona insaturada, que va ser hidrogenada per obtenir 127. Mitjançant una α- metilació es va obtenir la configuració requerida per stemospironina a C11. Les transformacions successives es van dur a terme de la mateixa manera que en la síntesi de 116 i 120, obtenint-se stemospironina i el seu anàleg 119. Les dades analítiques de l'stemospironina sintetitzada coincideixen totalment amb les descrites per l'alcaloide natural.The extracts of several plants of the Stemonaceae family have long been used in Asian countries against different diseases and for their antiparasitic properties. Significant constituents of these extracts are a series of structurally related secondary metabolites named as Stemona alkaloids. All the Stemona alkaloids are polycyclic and most of them present a central pyrrolo[1,2-a]azepine system as a characteristic structural feature. The majority also incorporate at least one substructure of α-methyl-γ-butyrolactone. Our research group designed a strategy in which the pyrroloazepine system is generated at an early stage of the sequence and the other specific fragments are then incorporated, with the aim of developing a flexible approach, with some intermediates being common precursors for various alkaloids. The typical pyrroloazepine core is synthesized through a 1,3-dipolar cycloaddition reaction between a chiral nitrone and an electrondeficient olefin. In this thesis, the syntheses of stemospironine and three new diastereoisomeric analogs, 116, 119 and 120 have been achieved. Thus, spirolactonization in the key intermediate 62 was accomplished by esterification of the tertiary alcohol followed by basic treatment of the phosphonate 86, yielding lactone 63. After removal of the silyl protection, the alcohol was oxidized, and the corresponding aldehyde was treated with ethyl bromomethylacrylate and zinc furnishing a 1:1 mixture of bislactones. Once the hydrogenation of C-C double bonds was accomplished, each bislactone was converted to amines 116 and 120, respectively. On the other hand, spirolactonization of 125 furnished an unsaturated lactone, which was hydrogenated to yield 127. A stereoselective α-methylation rendered the stemospironine-like configuration at C11. Then, the remaining transformations were performed as before, affording stemospironine and its analog 119. The analytical data of the synthetic stemospironine are in total agreement with those described for the natural alkaloid

On the Ancestral Compatibility of Two Phylogenetic Trees with Nested Taxa

Compatibility of phylogenetic trees is the most important concept underlying widely-used methods for assessing the agreement of different phylogenetic trees with overlapping taxa and combining them into common supertrees to reveal the tree of life. The notion of ancestral compatibility of phylogenetic trees with nested taxa was introduced by Semple et al in 2004. In this paper we analyze in detail the meaning of this compatibility from the points of view of the local structure of the trees, of the existence of embeddings into a common supertree, and of the joint properties of their cluster representations. Our analysis leads to a very simple polynomial-time algorithm for testing this compatibility, which we have implemented and is freely available for download from the BioPerl collection of Perl modules for computational biology.Comment: Submitte

Repellency of Aromatic Medicinal Plant Extracts and a Steam Distillate to Aedes aegypti

Volume: 2

Iodoaminations of alkenes

The activation of alkenes and their subsequent functionalization is a frequently used methodology in synthetic chemistry. This review highlights recent iodine-mediated aminations and elaborates on the various strategies to bring about regio- or stereoselective transformations

Distribution of sex forms in the phanerogamic flora

In the plant kingdom, particularly in the phanerogamic flora, hermaphroditism is by far the most common, yet the number of other sex forms is not negligible. This study was undertaken with the view of ascertaining the relative proportions in which such sex forms occur. For this purpose Engler and Prantls "Natürliche Pflanzenfamilien" with all the Nachträge (which are complete up to 1912) have been used. The lists that follow are the results of this examination

Unveiling the chromosomal architecture of Stemona tuberosa Lour.: first report of its karyotype and intra-generic investigation

The present investigation aims to provide a comprehensive understanding of the chromosomal architecture of Stemona tuberosa Lour, a plant species of high ethnobotanical significance belonging to the family Stemonceae. The study entailed a thorough examination of the chromosome number, which was determined to be 2n=14, with a basic number of X=7. Based on Stebbins’s categorization, the karyotype of S. tuberosa falls under 1B category, which indicates a relatively lower degree of asymmetry in chromosome complements. Moreover, the study also comprises various other karyomorphological indices, which may act as a significant key for intra-generic investigation of other species in the future. These findings offer new insights into the chromosomal makeup of S. tuberosa and could have potential implications for the conservation and utilization of this plant species

A bi‐organellar phylogenomic study of Pandanales: inference of higher‐order relationships and unusual rate‐variation patterns

We used a bi‐organellar phylogenomic approach to address higher‐order relationships in Pandanales, including the first molecular phylogenetic study of the panama‐hat family, Cyclanthaceae. Our genus‐level study of plastid and mitochondrial gene sets includes a comprehensive sampling of photosynthetic lineages across the order, and provides a framework for investigating clade ages, biogeographic hypotheses and organellar molecular evolution. Using multiple inference methods and both organellar genomes, we recovered mostly congruent and strongly supported relationships within and between families, including the placement of fully mycoheterotrophic Triuridaceae. Cyclanthaceae and Pandanaceae plastomes have slow substitution rates, contributing to weakly supported plastid‐based relationships in Cyclanthaceae. While generally slowly evolving, mitochondrial genomes exhibit sporadic rate elevation across the order. However, we infer well‐supported relationships even for slower evolving mitochondrial lineages in Cyclanthaceae. Clade age estimates across photosynthetic lineages are largely consistent with previous studies, are well correlated between the two organellar genomes (with slightly younger inferences from mitochondrial data), and support several biogeographic hypotheses. We show that rapidly evolving non‐photosynthetic lineages may bias age estimates upwards at neighbouring photosynthetic nodes, even using a relaxed clock model. Finally, we uncovered new genome structural variants in photosynthetic taxa at plastid inverted repeat boundaries that show promise as interfamilial phylogenetic markers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/33/cla12417-sup-0025-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/32/cla12417-sup-0017-FigS17.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/31/cla12417-sup-0004-FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/30/cla12417-sup-0019-FigS19.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/29/cla12417-sup-0020-FigS20.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/28/cla12417_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/27/cla12417-sup-0005-FigS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/26/cla12417-sup-0012-FigS12.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/25/cla12417-sup-0007-FigS7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/24/cla12417-sup-0022-FigS22.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/23/cla12417-sup-0029-TableS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/22/cla12417-sup-0010-FigS10.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/21/cla12417-sup-0011-FigS11.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/20/cla12417-sup-0014-FigS14.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/19/cla12417-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/18/cla12417-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/17/cla12417.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/16/cla12417-sup-0030-TableS6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/15/cla12417-sup-0021-FigS21.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/14/cla12417-sup-0023-FigS23.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/13/cla12417-sup-0009-FigS9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/12/cla12417-sup-0031-TableS7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/11/cla12417-sup-0006-FigS6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/10/cla12417-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/9/cla12417-sup-0024-FigS24.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/8/cla12417-sup-0008-FigS8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/7/cla12417-sup-0028-TableS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/6/cla12417-sup-0016-FigS16.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/5/cla12417-sup-0013-FigS13.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/4/cla12417-sup-0018-FigS18.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/3/cla12417-sup-0026-TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/2/cla12417-sup-0015-FigS15.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162810/1/cla12417-sup-0027-TableS3.pd

Probing Chemical Space with Alkaloid-Inspired Libraries

Screening of small molecule libraries is an important aspect of probe and drug discovery science. Numerous authors have suggested that bioactive natural products are attractive starting points for such libraries, due to their structural complexity and sp3-rich character. Here, we describe the construction of a screening library based on representative members of four families of biologically active alkaloids (Stemonaceae, the structurally related cyclindricine and lepadiformine families, lupin, and Amaryllidaceae). In each case, scaffolds were based on structures of the naturally occurring compounds or a close derivative. Scaffold preparation was pursued following the development of appropriate enabling chemical methods. Diversification provided 686 new compounds suitable for screening. The libraries thus prepared had structural characteristics, including sp3 content, comparable to a basis set of representative natural products and were highly rule-of-five compliant

The Chemistry Of Stemona Alkaloids: An Update.

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