250699-19-5Relevant academic research and scientific papers
Total synthesis and biological evaluation of pacidamycin D and its 3′-hydroxy analogue
Okamoto, Kazuya,Sakagami, Masahiro,Feng, Fei,Togame, Hiroko,Takemoto, Hiroshi,Ichikawa, Satoshi,Matsuda, Akira
, p. 1367 - 1377 (2012/03/27)
Full details of the total synthesis of pacidamycin D (4) and its 3′-hydroxy analogue 32 are described. The chemically labile Z-oxyacyl enamide moiety is the most challenging chemical structure found in uridylpeptide natural products. Key elements of our approach to the synthesis of 4 include the efficient and stereocontrolled construction of the Z-oxyvinyl halides 6 and 7 and their copper-catalyzed cross-coupling with the tetrapeptide carboxamide 5, a thermally unstable compound containing a number of potentially reactive functional groups. This synthetic route also allowed us to easily prepare 3′-hydroxy analogue 32. The assemblage by cross-coupling of the Z-oxyvinyl halide 6 and the carboxamide 5 at a late stage of the synthesis provided ready access to a range of uridylpeptide antibiotics and their analogues, despite their inherent labile nature with potential epimerization, simply by altering the tetrapeptide moiety.
A highly stereoselective samarium diiodide-promoted aldol reaction with 1′phenylseleno-2′-keto nucleosides. Synthesis of 1′α-branched uridine derivatives
Kodama, Tetsuya,Shuto, Satoshi,Ichikawa, Satoshi,Matsuda, Akira
, p. 7706 - 7715 (2007/10/03)
Since 1′-branched nucleosides are biologically important targets in medicinal chemistry, more efficient methods for preparing them are required. The 1′α-branched uridine derivatives were successfully synthesized via a samarium diiodide (SmI2)-promoted aldol reaction. Treatment of the 1′α-phenylseleno-2′-ketouridine derivative 6, readily prepared from uridine, with SmI2 at -78 °C in THF reductively cleaved the anomeric Se-C bond to generate the corresponding samarium enolate, which was highly stereoselectively condensed with aldehydes, such as PhCHO, MeCHO, i-PrCHO, or (CH2O)n, to give the corresponding 1′α-1″S-branched products 12a-d. This is the first time an enolate has been generated by reductively cleaving a C-Se bond. The highly selective stereochemical results suggest that the aldol reaction proceeds via a chelation-controlled transition state. When an excess of aldehyde was used and the reaction mixture was gradually warmed, the tandem aldol-Tishchenko reaction proceeded to give the "arabino-type" nucleosides 14a-c, having a 2′-"up" hydroxyl and 1′α-1″S-branched chain. 1′α-Hydroxymethyluridine (21), which is the uracil version of the antitumor antibiotic angustmycin C, was synthesized from the aldol reaction product 10.
Synthesis of chiral carbocyclic ribonucleotides
Antle, Vincent D.,Caperelli, Carol A.
, p. 1911 - 1928 (2007/10/03)
The carbocyclic analogs of CMP, UMP, GMP, IMP, and ribo-TMP, of the same absolute configuration as the naturally occurring β-D-ribofuranose-based ribonucleoside monophosphates, have been synthesized. The synthetic route employed Mitsunobu coupling of the
