263761-20-2Relevant academic research and scientific papers
Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step
Nocquet, Pierre-Antoine,Macé, Aurélie,Legros, Frédéric,Lebreton, Jacques,Dujardin, Gilles,Collet, Sylvain,Martel, Arnaud,Carboni, Bertrand,Carreaux, Fran?ois
supporting information, p. 2949 - 2955 (2018/12/13)
In this paper, a new access to several chiral 3-aminoglycals as potential precursors for glycosylated natural products is reported from a common starting material, (?)-methyl-L-lactate. The stereodivergent strategy is based on the implementation of a ring
Studies on the synthesis of landomycin A: Synthesis and glycosidation reactions of L-rhodinosyl acetate derivatives
Roush,Bennett,Roberts
, p. 6389 - 6393 (2007/10/03)
An efficient, eight-step synthesis of L-rhodinosyl acetate derivative 3 is described. The synthesis originates from methyl (S)-lactate and involves a highly stereoselective, chelate-controlled addition of allyltributylstannane to the lactaldehyde derivative 7. The β-anomeric configuration of 3 was established with high selectivity by acetylation of the pyranose precursor with Ac2O and Et3N in CH2Cl2. Preliminary studies of glycosidation reactions of 3 and L-rhodinosyl acetate 10 containing a 3-O-TES ether revealed that these compounds are highly reactive glycosidating agents and that trialkylsilyl triflates are effective glycosylation promoters. The best conditions for reactions with 15 as the accepter involved use of diethyl ether as the reaction solvent and 0.2 equiv of TES-OTf at -78°C. However, the TES ether protecting group of 10 proved to be too labile under these reaction conditions, and mixtures of 16a, 17, and 18a are obtained in reactions of 10 and 15. Disaccharide 17 arises via in situ cleavage of the TES ether of disaccharide 16a, while trisaccharide 18a results from a glycosidation of in situ generated 17 (or of 16a itself) with a second equivalent of 10. These problems were largely suppressed by using 3 with a 3-O-TBS ether protecting group as the glycosyl donor and 0.2 equiv of TES-OTf as the reaction promoter. Attempts to selectively glycosylate the C(3)-OH of diol acceptors 20 or 28 gave a 70:30 mixture of 21 and 22 in the reaction of 20 and a 43:27:30 mixture of regioisomeric trisaccharides 29 and 30 and tetrasaccharide 31 from the glycosidation reaction of 28. However, excellent results were obtained in the glycosidation of differentially protected disaccharide 34 using 1.5 equiv of 3 and 0.05 equiv of TBS-OTf in CH2-Cl2 at -78°C. The latter step is an important transformation in the recently reported synthesis of the landomycin A hexasaccharide unit.
The 12,13-diol cyclization approach for a truly stereocontrolled total synthesis of epothilone B and the synthesis of a conformationally restrained analogue
Martin, Harry J.,Pojarliev, Peter,Kaehlig, Hanspeter,Mulzer, Johann
, p. 2261 - 2271 (2007/10/03)
A highly convergent and stereocontrolled synthesis of epothilone B (1) has been developed. The epoxide moiety in 1 was generated by regioselective mesylation and base treatment of the 12,13-diol 30 which was formed by a chelate Cram controlled Grignard addition of 14 and methyl ketone 13. Both fragments were synthesized from the chiral carbon pool precursors (S)-citronellol and (S)-lactic acid, respectively. A highly diastereoselective aldol additon of epoxy-aldehyde 7 and the known Southern hemisphere ketone 8 delivered the full carbon skeleton, containing all the stereogenic centers of 1. Functional group manipulation, macrolactonization and removal of two protecting groups then yielded 1. The spatial closeness of the C4-β-methyl and C6-methyl group in the crystal structure of 1 inspired us to connect them through a methylene bridge to give a cyclohexanone derivative. Thus, the Northern hemisphere aldehyde 7 was added to the enolate of the cyclohexanone 47. Further manipulations and macrolactonization delivered the conformationally restrained epothilone derivative 42.
How stable are epoxides? A novel synthesis of epothilone B
Martin, Harry J.,Drescher, Martina,Mulzer, Johann
, p. 581 - 583 (2007/10/03)
Remarkable stability of the oxirane function is displayed over a number of synthetic operations in a novel synthesis of the antitumor compound epothilone B. The cis-epoxide, generated very early by dihydroxylation of an (E)-olefin, was resistant to more than ten synthetic steps under a wide variety of reaction conditions. TBS = tert-butyldimethylsilyl.
Epothilone B and its derivatives as novel antitumor drugs: Total and partial synthesis and biological evaluation
Mulzer, Johann
, p. 205 - 238 (2007/10/03)
Microtubule stabilizing natural products, as exemplified by paclitaxel (taxolR), are being considered as novel drugs against malignant therapy resistent solid tumors. Among these compounds, epothilone B and some of its derivatives have emerged as particularly promising candidates for industrial development. The total and partial syntheses of these compounds are described in detail, and some of the most important recent results on their biological activity are discussed.
