2007 Chemistry Highlights

korendovych · 28.12.2007 16:21:55

C&EN
DECEMBER 24, 2007 VOLUME 85, NUMBER 52 PP. 13-19
2007 Chemistry Highlights

pubs.acs.org/cen/coverstory/85/8552cover.html

korendovych · 29.12.2007 00:27:22

A new catalyst developed by M. Christina White and Mark S. Chen at the University of Illinois, Urbana-Champaign, simplifies the synthesis of highly complex organic molecules in an environmentally friendly way. The iron-based catalyst makes it possible to oxidize the unreactive aliphatic C–H bonds at tertiary carbons in complex molecules without the need for directing or activating groups (Science 2007, 318, 783). It uses hydrogen peroxide to oxidize C–H to C–OH bonds. Given a choice of C–H bonds in a complex molecule, it preferentially targets sterically accessible, electron-rich bonds at tertiary carbons. The researchers used the catalyst to oxidize the antimalarial natural product (+)-artemisinin primarily at only one of its five tertiary C–H bonds. The reaction not only eliminates the need for wasteful protecting groups but also produces water as the only catalytic by-product.

Новым катализатором назвать это сложно, скорее перепевы старых песен. Аналоги BPMEN давно уже использовались в катализе. Ларри Кей использовал железный комплекс для эпоксидирования. Когда Кристина еще была постдокшей у Якобсена они заметили, что при добавлении кислоты получается эпоксид без примесей диолов (JACS 123 (29): 7194-7195 JUL 25 2001). Теперь, они несколько изменили лиганд (добавив жесткости и стерики), получив более высокую селективность. Полезный урок дизайна лигандов. Я даже удивлен, что никто не сделал этого раньше, особенно учитывая количество людей, работающих над такими системами.

Интересно, что карьера Кристины после бесславного гарвадского периода резко пошла в гору. Был ли у них договор о разделении сфер влияния?

Відредаговано korendovych (29.12.2007 00:45:03)

korendovych · 29.12.2007 00:37:43

In molecular design, Alanna Schepartz and coworkers at Yale University created the first nonprotein oligomer found experimentally to look and act like a true protein (J. Am. Chem. Soc. 2007, 129, 1532). The structure, a β-peptide bundle, exhibits several hallmarks of real proteins, including exceptional stability, an interior core of hydrophobic amino acid side chains, and the ability to fold and unfold reversibly. The group made the structure by synthesizing an oligomer from 12 β-amino acids. The oligomer forms a helix with three faces, and the helices self-assemble into an octameric bundle. Complementary interactions between hydrophilic side chains on the bundle's surface appear to help it adopt its higher-order structure. The β-peptide bundle "is an important step toward a long-term goal of creating nonnatural molecules with the structure, function, and complexity of proteins," one observer noted.

Я не думаю, что здесь мы идеем дело с molecular design. Поэтому, насколько мне известно, эту статью не приняли в Nature. "...act like a true protein..." не знаю, безусловно, интересный пример, но закономерность ли это, или просто случайность покажет время.

korendovych · 29.12.2007 00:44:47

This year also saw major progress in the race to structurally characterize G-protein-coupled receptors (GPCRs). Although they are one of the most important families of proteins in the human body and a common target of drugs, GPCRs have been almost impossible to analyze structurally. Only one crystal GPCR structure, that of the light-sensitive protein rhodopsin, had been obtained. This year, two groups obtained the second GPCR structure, that of the human β2 adrenergic receptor (β2AR), by two different approaches.
Brian K. Kobilka of Stanford University School of Medicine and coworkers stabilized the protein for structural analysis by binding an antibody fragment to GPCR (Nature 2007, 450, 383; Nat. Methods 2007, 4, 927). And Kobilka, Raymond C. Stevens of Scripps, and coworkers enhanced β2AR's stability by linking the enzyme T4 lysozyme to it (Science 2007, 318, 1258 and 1266). Researchers will now try to adapt these approaches to solve the structures of other GPCRs more easily than has been possible before. Such a capability would have major implications for drug discovery and could lead to a better understanding of receptor biology.

Исключительно элегантные работы! Кто только не пытался их закристаллизовать! Полностью согласен с выделенной жирным шрифтом частью.

korendovych · 29.12.2007 00:53:43

Baran and coworkers found that some synthetic procedures are better off without protecting groups (Nature 2007, 446, 404). They carried out the total synthesis of (+)-ambiguine H without using protecting groups in only 10 steps—at least 10 steps shorter than with a conventional protection strategy. The protection-free approach enabled them to exploit the innate reactivity of a key indole group in an innovative way. And they synthesized welwitindolinone A by an eight-step protection-free sequence that is 17 steps shorter than another approach reported last year.

Красивый синтез от вундеркинда из Скриппса Фила Барана. Чем меньше защитныx групп, тем лучше.
Джон Порко написал о нем perspective.
Nature 446, 383-385 (22 March 2007) | doi:10.1038/446383a; Published online 21 March 2007

Відредаговано korendovych (29.12.2007 00:54:08)

korendovych · 29.12.2007 00:59:59

Вид из Лондона

Cutting-edge chemistry in 2007

www.rsc.org/chemistryworld/News/2007/De … 120702.asp

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2007 Chemistry Highlights

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