102989-24-2Relevant articles and documents
Convergent Total Synthesis of Asimicin via Decarbonylative Radical Dimerization
Kawamata, Takahiro,Yamaguchi, Akinori,Nagatomo, Masanori,Inoue, Masayuki
, p. 18907 - 18912 (2018)
Asimicin (1) exhibits potent antitumor activity and comprises a central C2-symmetric bis-tetrahydrofuran and two aliphatic side-chains, one of which terminates with (S)-methyl-2(5H)-furanone. This work reports a convergent total synthesis of 1 in 17 steps from d-gulose derivative 4. Decarbonylative radical-radial homo-coupling of α-alkoxyacyl telluride 12 a efficiently produced the C2-symmetric core 3-SS, which was transformed into 1 through stepwise attachment of the two side-chains and functional group manipulations.
Modular approach to Annonaceous acetogenins. Total synthesis of asimicin and bullatacin
Sinha, Subhash C.,Sinha-Bagchi, Anjana,Yazbak, Ahmad,Keinan, Ehud
, p. 9257 - 9260 (1995)
Starting with a variety of non-functionalized carbon skeletons and employing various combinations of five key transformations provides an easy access to most of the naturally occurring Annonaceous acetogenins. A particular emphasis is given to the dominant structural feature that appears in more than 40% of the known acetogenins. This is a linear, ten-carbon skeleton comprising two adjacent tetrahydrofurane rings flanked with two hydroxyl groups. Efficient, flexible syntheses of asimicin and bullatacin demonstrate this approach.
Alteration of the bis-tetrahydrofuran core stereochemistries in asimicin can affect the cytotoxicity
Sinha, Subhash C.,Chen, Zhiyong,Huang, Zheng-Zheng,Nakamaru-Ogiso, Eiko,Pietraszkiewicz, Halina,Edelstein, Matthew,Valeriote, Frederick
supporting information; experimental part, p. 7045 - 7048 (2009/11/30)
A systematic analysis using 10 synthetic asimicin stereoisomers revealed that the stereochemistry of the bis-tetrahydrofuran core, including the tetrahydrofuran rings and the adjacent hydroxy functions, had significant effect on its cytotoxicity. Our findings set to rest the highly controversial perception that the stereochemistry of the tetrahydrofuran core has little effect on the activity, which is not true for its cytotoxic effect, and also reinforces the previous conclusion that asimicin is a highly potent anticancer compound.
Total synthesis of asimicin via highly stereoselective [3 + 2] annulation reactions of substituted allylsilanes
Tinsley, Jennifer M.,Roush, William R.
, p. 10818 - 10819 (2007/10/03)
A highly stereoselective total synthesis of (+)-asimicin (1) is reported. The synthesis features two chelate-controlled [3 + 2] annulation reactions - one of which (e.g., 2 + 3) constitutes a key, convergent fragment assembly step - that establish all of the stereochemistry of the bis-tetrahydrofuran unit of the natural product. Copyright
A modular synthesis of annonaceous acetogenins
Marshall, James A.,Piettre, Arnaud,Paige, Mikell A.,Valeriote, Frederick
, p. 1771 - 1779 (2007/10/03)
A synthesis of four Annonaceous acetogenins, asiminocin, asimicin, asimin, and bullanin, by a modular approach from seven fundamental subunits, A-G, is described. The approach employs a central core aldehyde segment, C, to which are appended an aliphatic terminus, A or B, a spacer subunit, D or E, and a butenolide terminus, F or G. Coupling of the A, B, D, and E segments to the core aldehyde unit is effected by highly diastereoselective additions of enantiopure allylic indium or tin reagents. The butenolide termini are attached to the ACD, BCE, or BCD intermediates by means of a Sonogashira coupling. The design of the core, spacer, and termini subunits is such that any of the C30, C10, or C4 natural acetogenins or stereoisomers thereof could be prepared. IC50 values for the four aforementioned acetogenins against H-116 human colon cancer cells were found to be in the 10-3 to 10-4 μM range. The IC90 activities were ca. 10-3 μM for asimicin and asimin but only 0.1-1 μM for bullanin and asiminocin.
Total Synthesis of Asimicin and Bullatacin
Avedissian, Hovsep,Sinna, Santosh C.,Yazbak, Ahmad,Sinha, Anjana,Neogi, Partha,Sinha, Subhash C.,Keinan, Ehud
, p. 6035 - 6051 (2007/10/03)
The efficient total synthesis of asimicin, 1, and bullatacin, 2, has demonstrated the advantages of three different strategies for the synthesis of the tricyclic intermediates 6 and 7, which represent the key fragment of the bis-THF Annonaceous acetogenins. The naked carbon skeleton strategy is based on the production of all asymmetric centers by selective placement of the oxygen functions onto an unsaturated, nonfunctionalized carbon skeleton. Diversity in this approach arises from the relative timing of highly stereoselective reactions, such as the Sharpless asymmetric dihydroxylation (AD) reaction, the Kennedy oxidative cyclization (OC) with rhenium(VII) oxide, the Mitsunobu-type alcohol epimerization reaction, and the Williamson etherification reaction. The convergent strategy, which is based on the combinatorial coupling of two series of diastereomeric fragments, to produce intermediates such as 11 and 12, enjoys the advantages of both efficiency and versatility. The third approach, which is based on partially functionalized intermediates, such as 13, combines the advantages of both the linear and the convergent strategies-synthetic efficiency and diversity.
Total synthesis of the Annonaceous acetogenin (+)-asimicin. Development of a new bidirectional strategy
Marshall, James A.,Hinkle, Kevin W.
, p. 5989 - 5995 (2007/10/03)
The total synthesis of the Annonaceous acetogenin (+)-asimicin is described. The approach employs the (R)-α-OSEM allylic stannane 7 of >95% ee and the dialdehyde 8 obtained from (S,S)-diethyl tartrate. Addition of 7 to 8 in the presence of InCl3 afforded the bis-adduct 9 in 71% yield. Tosylation and treatment with TBAF led to the core bis-tetrahydrofuran intermediate, diol 11, in 78% yield. Mono tosylation (n-BuLi, TsCl, THF-DMSO) and subsequent hydrogenolysis with LiBEt3H gave alcohol 14. The iodide 15 was coupled with the higher-order vinylcyanocuprate to afford olefin 30. This was converted to diol 31 of high ee by the Sharpless protocol. This diol yielded the epoxide 33 via the mono-trisylate 32. Addition of (R)-lithio-2-(OTBS)-3- butyne in the presence of BF3·OEt2 afforded the alcohol 34. The SEM derivative 35 was treated with TBAF, and the resulting alcohol was converted to the butenolide 38 by a sequence involving treatment with (CF3CO)2O, then Pd(PPh3)4, CO, THF-H2O, and finally AgNO3/silica gel. Cleavage of the SEM protecting group with PPTS in ethanol afforded (+)-asimicin (39).
Total synthesis of the potent antitumor, bis-tetrahydrofuranyl annonaceous acetogenins (+)-asimicin and (+)-bullatacin
Hoye, Thomas R.,Tan, Lushi
, p. 1981 - 1984 (2007/10/02)
Convergent syntheses of the title compounds involve: a bis-THF-subunit preparation via Sharpless' double asymmetric dihydroxylation and subsequent asymmetric epoxidation; preparation of the C(4)-hydroxybutenolide-containing subunit using a Stille butenolide synthesis: Pd°-mediated coupling of these vinyl iodide and alkyne subunits; and selective Wilkinson reduction of the resulting enyne.
