Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• ][82][83][98][99]. The objective of the present effort was to obtain the target molecules by any means, as rapidly as possible, and in a fashion that might enable the production of analogs for structure–activity relationship studies. By contrast, our work on fredericamycin and nothapodytine had chiefly

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• company [3]. From structure–activity relationship (SAR) studies it was found that the addition of substituents at the 3- and 4-position of the pyrrole scaffold significantly increases potency when compared to the more classical 2,5-disubstituted pyrroles. This study culminated in the discovery of

A two step synthesis of a key unit B precursor of cryptophycins by asymmetric hydrogenation

• Benedikt Sammet,
• Mathilde Brax and
• Norbert Sewald

Beilstein J. Org. Chem. 2011, 7, 243–245, doi:10.3762/bjoc.7.32

• interacting with the β-subunit of α/β-tubulin heterodimers. Numerous natural and artificial analogs have been analysed in structure–activity relationship (SAR) studies. The unit B of cryptophycins contains a considerably modified D-tyrosine derivative (Figure 1). Substituent variations at unit B are not well

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• structure–activity relationship [49]. Federsel et al. used a piperazine derivative 6 and an aryl halide 5 for the preparation of a CNS-active substituted chiral aminotetralin 7 (Scheme 2) [50]. The 5-HT1B receptor antagonist 8 was developed for the treatment of certain neuronal disorders. Different

• important targets in the treatment of diabetes and dyslipidemia. Azetidinone acid derivatives 110 were discovered to be new subtype-selective PPARα/γ agonists. For detailed structure–activity relationship (SAR) studies, diversity was introduced very efficiently by a copper-mediated N-arylation of

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• comparison to Alogliptin in vitro. Nevertheless, to gain further insight we plan to conduct Structure-Activity-Relationship (SAR) studies for this class of compound that would eventually help to identify a potential lead possessing favorable pharmacological properties. Conclusion In conclusion, we have

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• pharmaceuticals A drug will bind its protein target with maximal affinity if it is pre-organised into the correct conformation prior to binding and this can be achieved in certain cases by judiciously incorporating fluorine atoms into the drug [4][17]. This concept is illustrated in structure–activity

• relationship studies of Indinavir (17, Figure 2), an HIV protease inhibitor developed by Merck. It is a functionalised pseudopeptide containing a central hydroxyethylene moiety in place of a scissile peptide bond. X-ray crystallography shows that 17 binds to HIV protease with its central carbon chain in an

An efficient partial synthesis of 4′-O-methylquercetin via regioselective protection and alkylation of quercetin

• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang,
• Jian-Ping Yang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2009, 5, No. 60, doi:10.3762/bjoc.5.60

• functions such as sulfate or glucuronide groups. These compounds will allow structure–activity relationship studies of flavonoids to be carried out. Their easily obtained labeled forms will give access to isotopic dilution dosage by LC-MS or LC-MS/MS and will help in the identification of unknown flavonoid

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• different strategies that have been employed to improve the efficacy of mitomycins in vivo by structure activity relationship studies. As a matter of fact, the natural products themselves are so sensitive that only minor modifications have been possible in connection with medicinal chemistry studies

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• only the first total synthesis of molecules of contemporary interest and syntheses that have helped to correct structures. In addition, some significant results on the novel synthesis and structure–activity relationship studies of annonaceous acetogenins are also introduced. Keywords: annonaceous

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• the lack of extensive toxicity tests from the latter two companies. Diterpene skeleton analogs Structure-activity relationship studies of sordarin have been largely confined to the glycosyl moiety, while the exact roles of the different components of the aglycone, such as the isopropyl group, the

Synthesis of crispine A analogues via an intramolecular Schmidt reaction

• Ajoy Kapat,
• Ponminor Senthil Kumar and
• Sundarababu Baskaran

Beilstein J. Org. Chem. 2007, 3, No. 49, doi:10.1186/1860-5397-3-49

• developed for the synthesis of crispine A. [20][21][22][23][24][25][26][27][28] Interestingly, Schell and Smith reported the first synthesis of crispine A, even before its isolation, using the N-chloramine rearrangement reaction as a key step.[25] In order to understand the structure activity relationship

Flexible synthesis of poison- frog alkaloids of the 5,8-disubstituted indolizidine- class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors

• Soushi Kobayashi,
• Naoki Toyooka,
• Dejun Zhou,
• Hiroshi Tsuneki,
• Tsutomu Wada,
• Toshiyasu Sasaoka,
• Hideki Sakai,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 30, doi:10.1186/1860-5397-3-30

• into brain and, as shown in our research, some exhibit high affinity and selectivity for either α4β2 or α7 nicotinic receptors. Further structure-activity relationship studies of synthetic indolizidines may lead to the development of radioactive α4β2-selective or α7-selective ligands useful for in vivo