Noteworthy observations accompanying synthesis of the apoptolidin disaccharide.
نویسندگان
چکیده
A stereoselective synthesis of the apoptolidin disaccharide is reported. The key chemistry features a new transformation utilizing a highly selective tetramethylalkoxyalanate[v]-directed syn-methylation of a vinylogous ester, isolation of a hydrate of a 2-keto sugar, an eco-friendly radical cleavage of a bromomethyl group, and an efficient preparation of a fluorodisaccharide via the use of XtalFluor-E.
منابع مشابه
Enantioselective synthesis of apoptolidin sugars.
[structure: see text] The de novo synthesis of the C9 and C27 sugar subunits (2) and (3), respectively, of the potent antitumor agent, apoptolidin, has been accomplished. A titanium tetrachloride-mediated asymmetric anti glycolate aldol addition was utilized to establish the 4' and 5' stereogenic centers of each of the three monosaccharides. Elaboration of the aldol adducts efficiently provided...
متن کاملTotal synthesis of apoptolidin A.
A highly convergent, enantioselective total synthesis of the potent antitumor agent apoptolidin A has been completed. The key transformations include highly selective glycosylations to attach the C27 disaccharide and the C9 6'-deoxy-l-glucose, a cross-metathesis to incorporate the C1-C10 trienoate unit, and a Yamaguchi macrolactonization to complete the macrocycle. Twelve stereocenters in the p...
متن کاملFluorescent probes of the apoptolidins and their utility in cellular localization studies.
Apoptolidin A has been described among the top 0.1% most-cell-selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20-membered macrolide with mono- and disaccharide moieties. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μM) when evaluated against several tumor cell lines. Apopto...
متن کاملTotal synthesis of apoptolidin: completion of the synthesis and analogue synthesis and evaluation.
The total synthesis of apoptolidin (1) is reported together with the design, synthesis, and biological evaluation of a number of analogues. The assembly of key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was supplemented by a second generation route to this advanced intermediate involving a Horner-Wadsworth-Emmons coupling of fragments 22 and 25. The final stages of the...
متن کاملApoptolidin, a selective cytotoxic agent, is an inhibitor of F0F1-ATPase.
BACKGROUND Apoptolidin is a macrolide originally identified on the basis of its ability to selectively kill E1A and E1A/E1B19K transformed rat glial cells while not killing untransformed glial cells. The goal of this study was to identify the molecular target of this newly discovered natural product. RESULTS Our approach to uncovering the mechanism of action of apoptolidin utilized a combinat...
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ورودعنوان ژورنال:
- Chemical communications
دوره 47 20 شماره
صفحات -
تاریخ انتشار 2011