Synthesis of the macrocyclic core of leiodermatolide.

The macrocyclic core (2) of the marine macrolide leiodermatolide (1) has been synthesized in 19 steps through a convergent strategy exploiting boron aldol methodology to install the requisite stereochemistry and a selective Stille coupling reaction for controlled fragment assembly, followed by a Yamaguchi macrolactonization and carbamate introduction at the C9-OH.

[1]  M. Maier,et al.  An approach to the core structure of leiodermatolide. , 2011, Organic letters.

[2]  R. Isbrucker,et al.  Leiodermatolide, a potent antimitotic macrolide from the marine sponge Leiodermatium sp. , 2011, Angewandte Chemie.

[3]  Heidi Ledford,et al.  Complex synthesis yields breast-cancer therapy , 2010, Nature.

[4]  S. Kan,et al.  Synthesis of the C1-C13 tetraenoate subunit of the chivosazoles. , 2010, Organic letters.

[5]  D. Newman,et al.  Impact of natural products on developing new anti-cancer agents. , 2009, Chemical reviews.

[6]  K. Nicolaou,et al.  From nature to the laboratory and into the clinic. , 2009, Bioorganic & medicinal chemistry.

[7]  M. Fuchter,et al.  One-pot formation of allylic chlorides from carbonyl derivatives. , 2008, Organic letters.

[8]  E. Anderson,et al.  Total synthesis of (-)-saliniketals A and B. , 2008, Organic letters.

[9]  A. Fürstner,et al.  A versatile protocol for Stille-Migita cross coupling reactions. , 2008, Chemical communications.

[10]  A. J. Blake,et al.  Enantioselective total syntheses of omuralide, 7-epi-omuralide, and (+)-lactacystin. , 2008, The Journal of organic chemistry.

[11]  Karl-Heinz Altmann,et al.  Anticancer drugs from nature--natural products as a unique source of new microtubule-stabilizing agents. , 2007, Natural product reports.

[12]  Ian Paterson,et al.  The Renaissance of Natural Products as Drug Candidates , 2005, Science.

[13]  K. Yeung,et al.  Actin-binding marine macrolides: total synthesis and biological importance. , 2002, Angewandte Chemie.

[14]  I. Paterson,et al.  A practical synthesis of (+)-discodermolide and analogues: fragment union by complex aldol reactions. , 2001, Journal of the American Chemical Society.

[15]  Gerlach,et al.  Total Synthesis of the Antimicrotubule Agent (+)-Discodermolide Using Boron-Mediated Aldol Reactions of Chiral Ketones. , 2000, Angewandte Chemie.

[16]  R. Kawahama,et al.  Stereoselective Hydrogenolysis of 1,1-Dibromo-1-alkenes and Stereospecific Synthesis of Conjugated (Z)-Alkenyl Compounds , 1998 .

[17]  I. Paterson.  Polyketide Synthesis Using the Boron-Mediated, anti-Aldol Reactions of Lactate-Derived Ketones: Total Synthesis of (-)-ACRL Toxin IIIB , 1998 .

[18]  Y. Zhong,et al.  Efficient and Facile Glycol Cleavage Oxidation Using Improved Silica Gel-Supported Sodium Metaperiodate. , 1997, The Journal of organic chemistry.

[19]  R. Kawahama,et al.  Palladium-Catalyzed Stereoselective Hydrogenolysis of Conjugated 1,1-Dibromo-1-alkenes to (Z)-1-Bromo-1-alkenes. An Application to Stepwise and One-Pot Synthesis of Enediynes and Dienynes , 1996 .

[20]  I. Paterson,et al.  Studies in polypropionate synthesis: High π-face selectivity in syn and anti aldol reactions of chiral boron enolates of lactate-derived ketones , 1994 .

[21]  T. Kusumi,et al.  High-field FT NMR application of Mosher's method. The absolute configurations of marine terpenoids , 1991 .

[22]  Davidr . Evans,et al.  Samarium-catalyzed intramolecular Tishchenko reduction of .beta.-hydroxy ketones. A stereoselective approach to the synthesis of differentiated anti 1,3-diol monoesters , 1990 .

[23]  J. Goodman,et al.  Enantio- and diastereoselective aldol reactions of achiral ethyl and methyl ketones with aldehydes: the use of enol diisopinocampheylborinates , 1990 .

[24]  K. Zhao,et al.  A stereoselective synthesis of (Z)-1-iodo-1-alkenes , 1989 .

[25]  I. Paterson,et al.  Aldol condensations of chiral ethylketones: Control by chiral boron reagents. , 1988 .

[26]  P. Kočovský.  Carbamates : A method of synthesis and some syntehtic applications , 1986 .

[27]  William Bauta,et al.  A regioselective entry to vinyllithiums from unsymmetrical ketones via enol triflates , 1986 .

[28]  E. Negishi,et al.  Controlled carbometalation. 20. Carbometalation reaction of alkynes with organoalene-zirconocene derivatives as a route to stereo-and regiodefined trisubstituted alkenes , 1985 .

[29]  E. Negishi,et al.  A versatile and selective route to difunctional trisubstituted (E)-alkene synthons via zirconium-catalyzed carboalumination of alkynes , 1981 .

[30]  T. Katsuki,et al.  A rapid esterification by means of mixed anhydride and its application to large-ring lactonization. , 1979 .

[31]  A. Lovey,et al.  Decarbalkoxylations of geminal diesters and β-keto esters in wet dimethyl sulfoxide. Effect of added sodium chloride on the decarbalkoxylation rates of mono- and di-substituted Malonate esters , 1974 .

[32]  B. Grenon,et al.  The decarbethoxylation of geminal dicarbethoxy compounds. , 1967, Tetrahedron letters.