136262-60-7Relevant academic research and scientific papers
Geldanamycin-inspired compounds induce direct trans-differentiation of human mesenchymal stem cells to neurons
Jogula, Srinivas,Soorneedi, Anand Ram,Gaddam, Jagan,Chamakuri, Srinivas,Deora, Girdhar Singh,Indarapu, Ranjith Kumar,Ramgopal, Murali Krishna,Dravida, Subhadra,Arya, Prabhat
, p. 110 - 116 (2017)
Inspired from geldanamycin, the synthesis of a new series of 20-membered macrocyclic compounds is developed. The key features in our design are (i) retention of the fragment having the precise chiral functional groups of geldanamycin at C10, C11, C12 and C14, and (ii) replacement of an olefin moiety with the ester group, and the quinoid sub-structure with the triazole ring. The southern fragment needed for the macrocyclic ring formation was obtained from Evans' syn aldol as the key reaction and with the use of D-mannitol as the cheap source of a chiral starting material. For the synthesis of the northern fragment, we utilized L-ascorbic acid, which provided the desired chiral functional groups at C6 and C7. Further, the chain extension completed the synthesis of the northern fragment. In our approach, the crucial 20 membered macrocyclic ring was formed employing the click chemistry. When tested for their ability to directly trans-differentiate human mesenchymal stem cells to neurons, two novel compounds (20a and 7) from this series were identified and this was further validated by the presence of specific neuronal biomarkers (i.e. nestin, agrin and RTN4).
Total synthesis of herbimycin A
Canova, Sophie,Bellosta, Veronique,Bigot, Antony,Mailliet, Patrick,Mignani, Serge,Cossy, Janine
, p. 145 - 148 (2007/10/03)
(Chemical Equation Presented) Hsp90 has recently emerged as a promising biological target for treatment of cancer. Herbimycin A and other members of the benzoquinoid ansamycin class of natural products are known to inhibit Hsp90 activity. The total synthesis of herbimycin A was achieved from the commercially available Roche ester 1 by using allylmetals to control the stereogenic centers at C6, C7, C10, C11, and C12 and a ring-closing metathesis to control the (Z)-double bond of the (E,Z)-dienic moiety.
