16094-44-3Relevant academic research and scientific papers
Total synthesis of landomycin A, a potent antitumor angucycline antibiotic
Yang, Xiaoyu,Fu, Boqiao,Yu, Biao
supporting information; experimental part, p. 12433 - 12435 (2011/10/02)
The first total synthesis of landomycin A, the longest and most potent antitumor angucycline antibiotic, has been achieved in 63 steps and 0.34% overall yield starting from 2,5-dihydroxybenzoic acid, 3,5-dimethylphenol, triacetyl d-glucal, and d-xylose, with a convergent linear sequence of 21 steps.
Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: A scaffold hopping approach using salicylate and catechol groups
Fan, Xing,Zhang, Feng-Hua,Al-Safi, Rasha I.,Zeng, Li-Fan,Shabaik, Yumna,Debnath, Bikash,Sanchez, Tino W.,Odde, Srinivas,Neamati, Nouri,Long, Ya-Qiu
experimental part, p. 4935 - 4952 (2011/09/30)
HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well mechanistically different. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC50 = 5 μM) with more than 40-fold selectivity for the strand transfer over the 3′-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3- dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC50 value of 8 μM. Using molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. Furthermore, the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site on IN. This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors.
Approaches to the preparation of 4-benzyloxy-2-(α,α,α- D3)methylphenol, a building block for labeled δ-tocopherol, and a new synthesis of R,R,R-5-D3-α-tocopherol
Mazzini, Francesco,Mandoli, Alessandro,Salvadori, Piero,Netscher, Thomas,Rosenau, Thomas
, p. 4864 - 4869 (2007/10/03)
Different routes are described for the synthesis of 4-benzyloxy-2-D 3-phenol, a key building block in the preparation of D 3-δ-tocopherol. Conditions for the improvement of Minami's reduction are also given, allowing a straightforward route to the title compound and a new synthesis of R,R,R-5-D3-α-tocopherol in good yields, starting from widely available R,R,R-α-tocopherol. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
SYNTHESIS OF PEPTIDE ALKALOIDS-III. AMINO ACIDS AND PEPTIDES-XXXII. SYNTHESIS OF DIHYDRO-ZIZYPHINE A AND B
Schmidt, Ulrich,Boekens, Hilmar,Lieberknecht, Albrecht,Griesser, Helmut
, p. 4949 - 4952 (2007/10/02)
Recently we described a new cyclisation method for the synthesis of ansa peptides by hydrogenolysis of Z-pentafluorophenyl ester and ring closure on the surface of the palladium catalyst.We applied this reaction to the synthesis of the 14-membered ansa pe
