H2020Индивидуална стипендия2017–2019

GRITAP · A General Strategy for the Iterative Assembly of Complex 1,3-Polyol Motifs

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-07-01 → 2019-06-30
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Нов метод за синтез на сложни молекули (1,3-полиоли) позволява по-бързото създаване на вещества като природния продукт bahamaolide A. По-кратките процеси намаляват разходите и отпадъците, което улеснява производството на нови лекарствени средства в голям мащаб.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

A General Strategy for the Iterative Assembly of Complex 1,3-Polyol Motifs

We achieve the development of an iterative chain growth strategy for the synthesis of any 1,3-polyol motif with tailored shapes. The proposed method will allow complete control over the relative and absolute stereochemistry of both non-symmetric and C2-symmetric 1,3-polyols. The power of this methodology will be exemplified through its application to the synthesis of the highly complex polyacetate natural product, bahamaolide A for the first time in less than 15 steps from a cheap commodity 1,4-pentadiene (a protecting-group-free approach). This project seeks to develop new shorter routes to synthesize medicinally important natural products and their analogues, a reduction in the number of steps will not only reduce the cost, but also make larger scale production feasible. We also expect to have the opportunity to participate in early process to identify molecules which possess suitable characteristics to make potential drug through the cooperation with other scientific groups in the future. Therefore, the fellowship will have a direct impact on EU society and economy not only because it will facilitate the synthesis of complex structural motifs (leading to less waste- economic) but also because the generation of new drug-like molecules has the potential to benefit the population (societal).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

An attractive approach to preparing molecules with common repeat units is iterative synthesis, an approach that is extensively used by Nature in the synthesis of large biomolecules. Nature also uses this tactic for small-molecule synthesis even though common repeat units are not always immediately apparent, the archetypical example being polyketide synthesis. In contrast, iterative strategies in chemical synthesis are often much less efficient requiring several functional-group interconversions and purifications between chain-extension steps. We recently reported an “Assembly Line Synthesis” method for the iterative, reagent-controlled homologation (chain extension) of a boronic ester. This process enabled the conversion of a simple boronic ester into a molecule bearing 10 contiguous methyl substituents in an effectively “one-pot” process. Whilst these methyl-rich carbon chains are rare in natural products, hydroxyl-rich carbon chains (1,3-polyols) are ubiquitous and often show pronounced and useful biological activity. It would therefore be very useful if this or a related strategy could be applied to the fully stereocontrolled synthesis of 1,3-polyols. Herein, we outline a general strategy for the synthesis of 1,3-polyols that hinges on the merging of two well-established methodologies: lithiation–borylation and catalytic diboration. We expect to achieve complete control over both relative and absolute stereochemistry in the iterative synthesis of 1,3-polyboronic esters, enabling stereochemistry to be essentially dialled-in. Subsequent oxidation of the boron esters reveals the desired 1,3-related polyol. The strategy will be applied to the total synthesis of one of the most complex polyols known, bahamaolide A, a macrocyclic polyol–polyene natural product with potent antifungal properties. This strategy promises to be the most efficient synthetic route to these highly biologically active and hugely important class of compounds.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY OF BRISTOL · BRISTOLКоординаторОбединеното кралство