Redox Economy in Organic Synthesis Burns, Noah Z; Baran, Phil S; Hoffmann, Reinhard W
Angewandte Chemie (International ed.),
April 6, 2009, Letnik:
48, Številka:
16
Journal Article
Recenzirano
Stimulus package for organic synthesis: The economy of step and atom usage has been widely reviewed and acknowledged as being useful frameworks to evaluate the efficiency of synthesis. This Review ...brings to attention another form of economy which should be considered in the planning and evaluation of a multistep synthesis: redox economy. Several guidelines and examples are included to illustrate the logic of this approach and to stimulate the design of syntheses."Economy" is referred to as the thrifty and efficient use of material resources, as the principle of "minimum effort to reach a goal." More illuminating is: "the aim to portion one's forces in order to use as little as possible of them to reach a goal." Such statements certainly apply when the goal is to synthesize a complex target molecule. Redox economy then implies the use of as few redox steps as possible in the synthetic conquest of a target compound. While any sort of economy will help to streamline the effort of total synthesis, redox economy addresses a particularly weak area in present-day total synthesis. It is not enough to point out the present deficiencies, rather the purpose of this Review is to serve as a teaching tool for all practitioners of the field by giving and illustrating guidelines to increase redox economy in multistep organic synthesis.
The economies of synthesis Newhouse, Timothy; Baran, Phil S; Hoffmann, Reinhard W
Chemical Society reviews
38, Številka:
11
Journal Article
Recenzirano
Odprti dostop
In this tutorial review the economies of synthesis are analysed from both detailed and macroscopic perspectives, using case-studies from complex molecule synthesis. Atom, step, and redox economy are ...more than philosophical constructs, but rather guidelines, which enable the synthetic chemist to design and execute an efficient synthesis. Students entering the field of synthesis might find this tutorial helpful for understanding the subtle differences between these economic principles and also see real-world situations where such principles are put into practice.
For almost 200 years, the synthesis of natural products has been practiced. In this time span, not only the target structures have become increasingly more complex (see two examples from the 1970s), ...the objectives of natural product synthesis have also changed. Likewise, the standards and criteria for the conduction of natural product synthesis have changed. It is these changes that form the subject of this Essay.
A key challenge in the synthesis of diterpenoid alkaloids lies in identifying strategies that rapidly construct their multiply bridged polycyclic skeletons. Existing approaches to these structurally ...intricate secondary metabolites are discussed in the context of a “bond‐network analysis” of molecular frameworks, which was originally devised by Corey some 40 years ago. The retrosynthesis plans that emerge from a topological analysis of the highly bridged frameworks of the diterpenoid alkaloids are discussed in the context of eight recent syntheses of hetidine and hetisine natural products and their derivatives. This Minireview highlights the extent to which network analyses of the type described here sufficed for designing synthesis plans, as well as areas where they had to be amalgamated with functional group oriented synthetic planning considerations.
A key challenge in the synthesis of diterpenoid alkaloids lies in identifying efficient strategies to construct their multiply bridged polycyclic skeletons. Approaches from eight recent syntheses are discussed in the context of “bond‐network analyses”, highlighting the efficacy of bond‐network analyses for synthesis planning, as well as where other considerations had to be incorporated.
A "Hot, Energized" Benzyne Hoffmann, Reinhard W.; Suzuki, Keisuke
Angewandte Chemie (International ed.),
March 4, 2013, Letnik:
52, Številka:
10
Journal Article
Recenzirano
Fundamental aspects of chemically activated reactive intermediates can possibly be learned from the novel generation of arynes. The intramolecular 4+2 cycloaddition between a diyne and an ...(electronically activated) alkyne also provides a new route to generate arynes (see scheme).
Two carbenoids combine to generate an olefin by a mechanism involving formation of an ate complex, 1,2‐metalate rearrangement, and β‐elimination. As each stage of this eliminative coupling is ...stereospecific, the overall stereochemical outcome can be understood and, in principle fully controlled, providing that the absolute stereochemical configurations of the reacting carbenoid species are defined. In contrast to traditional alkene syntheses, the eliminative cross‐coupling of carbenoids offers a connective approach to olefins capable of precisely targeting a given isomer regardless of the nature of the features distinguishing the isomers. The formation of olefins by the eliminative dimerization and eliminative cross‐coupling of carbenoids is reviewed with a range of illustrative examples, including the reactions of α‐lithiated haloalkanes, epoxides, and carbamates. An emphasis is placed on stereochemical analysis and methods to generate sp3‐hybridized carbenoids in stereodefined form are surveyed.
Mutual elimination of electrofugal (M) and nucleofugal (X) leaving groups from pairs of reacting carbenoids results in the generation of a C−C double bond. This eliminative coupling process is inherently regio‐ and stereospecific and offers a programmable synthesis of olefins. Homo‐ and cross‐coupling variants are reviewed and prospects for further development are highlighted.
Complex Molecule Synthesis, a Personal View Hoffmann, Reinhard W.
Israel journal of chemistry,
February 2018, 2018-02-00, 20180201, Letnik:
58, Številka:
1-2
Journal Article
Recenzirano
Our ability to synthesize complex molecules reflects the capabilities and status of synthetic methodology at a given time. Accordingly the targets of actual syntheses have become ever more ...challenging over the last fifty years. This is showcased in this review with reference to five syntheses, the author chose as his personal preference.
Autoimmune diseases commonly feature the presence of specific humoral autoantibodies. However, the prevalence of a large panel of systemic autoantibodies has never been assessed in the general ...population. We, therefore, described the prevalence of about 50 humoral systemic autoantibodies in a sample of the general Bavarian adult population.
Non-fasting venous serum samples from 331 participants were analyzed for 7 autoantibody screening tests (nuclear, cytoplasmic, and mitotic ANA, ANCA, cANCA and pANCA, anti-ENA autoantibodies) and 44 different monospecific humoral non-organ specific/systemic autoantibodies using indirect immunofluorescence tests, ELISAs, and line blots. In order to assess associations between sex, age, BMI, education level, smoking status and the presence of systemic autoantibodies, logistic regression analyses were conducted.
At least one screening test was positive in 29.9% of the participants, and 42.3% of the participants were seropositive for at least one monospecific autoantibody. The most frequently found monospecific autoantibodies were rheumatoid factor (35.6%), ß2-glycoprotein 1 IgM (4.8%), and cardiolipin IgG (1.8%). Only few associations between sex, age, BMI, education, smoking status and autoantibody frequencies were observed.
Systemic autoantibodies are common in the general Bavarian population, and largely independent of sex, age, BMI, education, or smoking status. The study results may give orientation to clinicians about the occurrence of autoantibodies in the population, not (yet) associated with clinical symptoms.
The gene encoding the miR-34a microRNA is a transcriptional target of the p53 tumor suppressor protein and subject to epigenetic inactivation in colorectal cancer and numerous other tumor types. ...Here, we combined pulsed SILAC (pSILAC) and microarray analyses to identify miR-34a-induced changes in protein and mRNA expression. pSILAC allowed to quantify the de novo protein synthesis of 1206 proteins after activation of a conditional miR-34a allele in a colorectal cancer cell line. ∼19% of the detected proteins were differentially regulated, with 113 proteins being down- and 115 up-regulated. The proteins with a miR-34a seed-matching-sequence in the 3′-untranslated region (UTR) of the corresponding mRNA showed a clear bias toward translational repression. Proteins involved in DNA replication, e.g. the MCM proteins, and cell proliferation, were over-represented among indirectly down-regulated proteins lacking a miR-34a seed-match. The decrease in de novo protein synthesis of direct miR-34a targets correlated with reduced levels of the corresponding mRNA in most cases, indicating an interdependence of both types of regulation. In addition, 43 mRNAs encoding proteins not detected by pSILAC were down-regulated after miR-34a expression and contained miR-34a seed-matches. The direct regulation of selected miR-34a target-mRNAs was confirmed using reporter assays. Via down-regulation of the proteins encoded by these mRNAs miR-34a presumably inhibits glycolysis (LDHA), WNT-signaling (LEF1), invasion/migration (AXL) and lipid metabolism (ACSL1, ACSL4). Furthermore, miR-34a may activate p53 by inhibiting its acetylation (MTA2, HDAC1) and degradation (YY1). In summary, miR-34a presumably participates in multiple tumor suppressive pathways by directly and indirectly suppressing the expression of numerous, critical proteins.
We present a catalyst‐free method for indirect C−F activation of a perfluorinated side chain in C(3) position of 1H‐indoles with moderate to good yields, which allows the introduction of a ...nucleophile at the α‐CF2‐group of the perfluorinated chain. By adapting this approach, it is also possible to modify 3‐perfluorobutyl‐2‐phenyl‐1H‐indole to generate privileged structures for medicinal chemistry.
A method for activating the α‐CF2‐group of 3‐perfluorobutyl‐1H‐indoles without catalyst is presented, enabling the preparation of fluorine‐containing 3‐substituted‐2‐phenylindoles, which are preferred structures for medicinal chemistry.
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