177958-01-9Relevant academic research and scientific papers
Total synthesis of an enantiomeric pair of FR900482. 3. Completion of the synthesis by assembling the two segments
Katoh, Tadashi,Nagata, Yuriko,Yoshino, Toshiharu,Nakatani, Shogo,Terashima, Shiro
, p. 10253 - 10270 (2007/10/03)
The title synthesis was accomplished by a method which features (i) coupling of the aromatic segment 2 with the enantiomerically pure aliphatic segment 3 to install the requisite carbon unit (2+3→4); (ii) intramolecular aldol reaction of the highly functionalized dialdehyde 10 to elaborate the desired eight-membered ring system 12 (10→12); (iii) epimerization at the C-8 position of the hydroxy ketone 15 to obtain the correct stereochemistry (15→16); (iv) internal hemiacetal formation of the N-hydroxylamino ketone 25 in situ generated from the ketone 24 to construct the requisite tetracyclic ring system 26 (24→25→26) as the key steps. The in vitro cytotoxicity assay of the synthesized compounds (1, ent-1, 31, ent-31, 32, and ent-32) against P388 murine leukemia cells disclosed that FR900482 (1) and its congeners 31, 32 bearing natural absolute configuration are 100 times more cytotoxic than the corresponding unnatural enantiomers (ent-1, ent-31, ent-32).
Total synthesis of natural (+)-FR900482. 3. Completion of the synthesis
Katoh, Tadashi,Yoshino, Toshiharu,Nagata, Yuriko,Nakatani, Shogo,Terashima, Shiro
, p. 3479 - 3482 (2007/10/03)
The title synthesis was accomplished by featuring (i) coupling of the aromatic fragment 2 with the optically active aliphatic fragment 3 to install the requisite carbon unit (2+3 → 4); (ii) intramolecular aldol reaction of the highly functionalized dialdehyde 10 to produce the desired eight-membered ring system 11 (10 → 11); (iii) epimerization of the C-7 position of hydroxy ketone 14 to obtain the correct stereochemistry (14 → 15); (iv) internal hemiacetal formation of hydroxylamino ketone 23 in situ generated from ketone 22 to construct the requisite tetracyclic ring system 24 (23 → 24) as key steps.
