119879-74-2Relevant academic research and scientific papers
The migrastatin family: Discovery of potent cell migration inhibitors by chemical synthesis
Gaul, Christoph,Njardarson, Jon T.,Shan, Dandan,Dorn, David C.,Wu, Kai-Da,Tong, William P.,Huang, Xin-Yun,Moore, Malcolm A. S.,Danishefsky, Samuel J.
, p. 11326 - 11337 (2007/10/03)
The first asymmetric total synthesis of (+)-migrastatin (1), a macrolide natural product with antimetastatic properties, has been accomplished. Our concise and flexible approach utilized a Lewis acid-catalyzed diene aldehyde condensation (LACDAC) to install the three contiguous stereocenters and the trisubstituted (Z)-alkene of migrastatin (2 + 3 → 21). Construction of the two remaining stereocenters and incorporation of the glutarimide-containing side chain was achieved by an anti-selective aldol addition of propionyl oxazolidinone 28 to angelic aldehyde 27, followed by a Horner-Wadsworth-Emmons (HWE) coupling of 32 with glutarimide aldehyde 5. Finally, the assembly of the macrocycle was realized by a highly (E)-selective ring-closing metathesis (35 → 37). Utilizing the power of diverted total synthesis (DTS), a series of otherwise inaccessible analogues was prepared and evaluated for their potential as tumor cell migration inhibitors in several in vitro assays. These studies revealed a dramatic increase in activity when the natural motif was considerably simplified, presenting macrolactones 45 and 48, as well as macrolactam 55, macroketone 60, and CF3-alcohol 71 as promising anti-metastatic agents.
Synthesis of the macrolide core of migrastatin
Gaul, Christoph,Danishefsky, Samuel J.
, p. 9039 - 9042 (2007/10/03)
A concise and efficient synthesis of the macrolactone core of migrastatin, a new natural product with potent anticancer properties, has been achieved. The key features of our synthetic strategy encompass a Lewis acid catalyzed diene aldehyde condensation
Synthesis and triplex forming properties of an acyclic N7-glycosylated guanine nucleoside
St. Clair, Aimee,Xiang, Guobing,McLaughlin, Larry W.
, p. 925 - 937 (2007/10/03)
A chiral acyclic nucleoside, one in which the ribose carbohydrate has been replaced with a glycerol-based linker, is prepared by glycosylating guanine at the N7-nitrogen. The stereochemically pure derivative is converted to a DMT-protected phosphoramidite for incorporation into DNA sequences. Sequence containing the acyclic N7-dG nucleoside are capable of forming DNA triplexes in which it is likely that the N1-H and N2-amino groups of the N7-dG are involved in recognition of the guanine base in G-C base pairs.
A cytosine analogue containing a conformationally flexible acyclic linker for triplex formation at sites with contiguous G-C base pairs
Xiang, Guobing,McLaughlin, Larry W.
, p. 375 - 392 (2007/10/03)
Two nucleoside derivatives of the pyrimidine bases T and m(5ox)C have been prepared with flexible acyclic carbohydrate linkers. A new procedure, beginning with (R)-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol permits the preparation of the stereochemically pure acyclic derivatives of both protected nucleoside analogues without contamination by a problematic rearrangement product. By simply increasing the flexibility of the carbohydrate portion of the am(5ox)C nucleoside derivative. 15-mer triplexes containing five contiguous G-C base pairs exhibit a 7-8 °C increase in T(m) value.
