Evolution of the total synthesis of (-)-okilactomycin exploiting a tandem oxy-cope rearrangement/oxidation, a Petasis-Ferrier union/rearrangement, and ring-closing metathesis.

An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the 13-membered macrocycle ring, employing for the first time a sterically demanding acetal, an intramolecular chemoselective acylation to access an embedded bicyclic lactone, and an efficient ring-closing metathesis (RCM) reaction to generate the macrocyclic ring.

[1]  Thomas M. Razler,et al.  Evolution of the Petasis-Ferrier union/rearrangement tactic: construction of architecturally complex natural products possessing the ubiquitous cis-2,6-substituted tetrahydropyran structural element. , 2008, Accounts of chemical research.

[2]  Amos B. Smith,et al.  Total synthesis of (-)-okilactomycin. , 2007, Journal of the American Chemical Society.

[3]  Isidro M. Pastor and Miguel Yus.  The Prins Reaction: Advances and Applications , 2007 .

[4]  S. Ley,et al.  Oxidation of Activated Halides to Aldehydes and Ketones by N-Methylmorpholine-N-oxide , 2006 .

[5]  A. Gradillas,et al.  Macrocyclization by ring-closing metathesis in the total synthesis of natural products: reaction conditions and limitations. , 2006, Angewandte Chemie.

[6]  S. Marque,et al.  Synthetic studies toward highly functionalized 5beta-lanosterol derivatives: a versatile approach utilizing anionic cycloaddition. , 2006, The Journal of organic chemistry.

[7]  Amos B. Smith,et al.  Total synthesis of the marine natural product (-)-clavosolide A. A showcase for the Petasis-Ferrier union/rearrangement tactic. , 2006, Organic letters.

[8]  Fatima Rivas,et al.  Synthetic studies toward the zoanthamine alkaloids: synthesis of the fully functionalized BC ring motif , 2005 .

[9]  J. Buynak,et al.  Synthesis and Evaluation of 3-(Carboxymethylidene)- and 3-(Carboxymethyl)penicillinates as Inhibitors of β-Lactamase , 2005 .

[10]  E. Meyer,et al.  Total synthesis of (-)-kendomycin exploiting a Petasis-Ferrier rearrangement/ring-closing olefin metathesis synthetic strategy. , 2005, Journal of the American Chemical Society.

[11]  K. Minbiole,et al.  A cyclopropane fragmentation approach to heterocycle assembly: a convergent synthesis of oxepanes. , 2005, Organic letters.

[12]  D. Gotchev,et al.  Spongistatin synthetic studies. evolution of a scalable synthesis for the EF fragment of (+)-Spongistatin 1 exploiting a Petasis-Ferrier union/rearrangement tactic. , 2004, Organic letters.

[13]  Richard E. Taylor,et al.  Enantioselective preparation of the C1-C11 fragment of apoptolidin. , 2004, Organic letters.

[14]  J. Deschamps,et al.  General approach for the synthesis of sarpagine indole alkaloids. Enantiospecific total synthesis of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, (+)-Na-methylvellosimine, and (+)-Na-methyl-16-epipericyclivine. , 2003, The Journal of organic chemistry.

[15]  W. Hakamata,et al.  Convenient preparation of cyclic acetals, using diols, TMS-source, and a catalytic amount of TMSOTf. , 2003, The Journal of organic chemistry.

[16]  Pradeep Kumar,et al.  PCC-mediated novel oxidation reactions of homobenzylic and homoallylic alcohols , 2003 .

[17]  Amos B. Smith,et al.  Total syntheses of (+)-zampanolide and (+)-dactylolide exploiting a unified strategy. , 2002, Journal of the American Chemical Society.

[18]  E. Mernyák,et al.  Synthesis of novel halogen-containing d-homoestrone and 13α-d-homoestrone derivatives by Lewis acid-induced intramolecular Prins reaction , 2002 .

[19]  S. Boulet,et al.  Toward a Total Synthesis of Okilactomycin. 1. A Direct, Enantiocontrolled Route to the Western Sector , 2002 .

[20]  K. Steliou,et al.  Synthetic studies toward bioactive cyclic peroxides from the marine sponge Plakortis angulospiculatus. , 2002, Organic letters.

[21]  S. Akinaga,et al.  Chrolactomycin, a novel antitumor antibiotic produced by Streptomyces sp. , 2001, The Journal of antibiotics.

[22]  P. Verhoest,et al.  Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement. , 2001, Journal of the American Chemical Society.

[23]  A. Hoveyda,et al.  Efficient and Recyclable Monomeric and Dendritic Ru-Based Metathesis Catalysts , 2000 .

[24]  J. Alderfer,et al.  Use of 1,2-dichloro 4,5-dicyanoquinone (DDQ) for cleavage of the 2-naphthylmethyl (NAP) group , 2000 .

[25]  S. Kozmin,et al.  Chiral Amino Siloxy Dienes in the Diels−Alder Reaction: Applications to the Asymmetric Synthesis of 4-Substituted and 4,5-Disubstituted Cyclohexenones and the Total Synthesis of (−)-α-Elemene , 1999 .

[26]  P. Verhoest,et al.  Phorboxazole synthetic studies. 1. Construction of a C(3-19) subtarget exploiting an extension of the Petasis-Ferrier rearrangement. , 1999, Organic letters.

[27]  P. Verhoest,et al.  Phorboxazole synthetic studies. 2. Construction of a C(20-28) subtarget, a further extension of the Petasis-Ferrier rearrangement. , 1999, Organic letters.

[28]  E. Corey,et al.  Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method. , 1998, Angewandte Chemie.

[29]  M. Gaunt,et al.  Rational Design of Benzyl-Type Protecting Groups Allows Sequential Deprotection of Hydroxyl Groups by Catalytic Hydrogenolysis , 1998 .

[30]  A. Tebbe,et al.  The First Synthesis of a Daphnane Diterpene: The Enantiocontrolled Total Synthesis of (+)-Resiniferatoxin , 1997 .

[31]  L. Paquette.  Recent applications of anionic oxy-cope rearrangements , 1997 .

[32]  S. Kozmin,et al.  Preparation and Diels−Alder Reactivity of 1-Amino-3-siloxy-1,3-butadienes , 1997 .

[33]  S. Kozmin,et al.  Asymmetric Diels−Alder Reactions of Chiral 1-Amino-3-siloxy-1,3-butadiene: Application to the Enantioselective Synthesis of (−)-α-Elemene , 1997 .

[34]  Andrew Kopecky,et al.  Pseudoephedrine as a Practical Chiral Auxiliary for the Synthesis of Highly Enantiomerically Enriched Carboxylic Acids, Alcohols, Aldehydes, and Ketones , 1997 .

[35]  N. Petasis,et al.  Stereocontrolled synthesis of substituted tetrahydropyrans from 1,3-dioxan-4-ones , 1996 .

[36]  R. Ferrier,et al.  THE CONVERSION OF CARBOHYDRATE DERIVATIVES INTO FUNCTIONALIZED CYCLOHEXANES AND CYCLOPENTANES , 1993 .

[37]  F. A. Davis,et al.  Asymmetric hydroxylation of enolates with N-sulfonyloxaziridines , 1992 .

[38]  S. Schreiber,et al.  Total synthesis of (-)-hikizimycin employing the strategy of two-directional chain synthesis , 1992 .

[39]  K. Takeda,et al.  A Lewis acid mediated intramolecular [2+2] cycloaddition of 3-(9-methylundeca-7,9-dienyl)-9-methylene-2,8-dioxabicyclo [4.3.0] nonane-5,7-dione , 1992 .

[40]  C. Paulmier,et al.  Phenylselenoazidation of Conjugated Enals. Allylic Rearrangement of 2-Alkylidene-3-azidopropanals and Propionic Acids , 1991 .

[41]  A. Holmes,et al.  Studies towards the synthesis of obtusenyne. A Claisen rearrangement approach to unsaturated nine-membered lactones. , 1991 .

[42]  R. Hirsenkorn,et al.  Functionally substituted vinyl carbanions, 42. Synthesis of the top half of chlorothricolide , 1990 .

[43]  N. Petasis,et al.  Titanium-mediated carbonyl olefinations. 1. Methylenations of carbonyl compounds with dimethyltitanocene , 1990 .

[44]  B. Ganem,et al.  Ready oxidation of halides to aldehydes using trimethylamine N-oxide in dimethylsulfoxide , 1990 .

[45]  S. Ōmura,et al.  Biosynthesis of the antibiotic okilactomycin. , 1989, The Journal of antibiotics.

[46]  E. Corey,et al.  Practical enantioselective Diels-Alder and aldol reactions using a new chiral controller system , 1989 .

[47]  F. Matsuda,et al.  Stereocontrolled total synthesis of (+)-pederine , 1988 .

[48]  T. Saito,et al.  Okilactomycin, a novel antibiotic produced by a Streptomyces species. I. Taxonomy, fermentation, isolation and characterization. , 1987, The Journal of antibiotics.

[49]  T. Furuya,et al.  Okilactomycin, a novel antibiotic produced by a Streptomyces species. II. Structure determination. , 1987, The Journal of antibiotics.

[50]  B. Šolaja,et al.  The synthesis of (±)-isoptychanolide by application of the α-alkynone cyclisation , 1987 .

[51]  J. Vederas,et al.  Oxidation of enolates by dibenzyl peroxydicarbonate to carbonates of .alpha.-hydroxy carbonyl compounds , 1986 .

[52]  J. Stille,et al.  Palladium-catalyzed formylation of organic halides with carbon monoxide and tin hydride. , 1986, Journal of the American Chemical Society.

[53]  W. Scott,et al.  A Convenient Synthesis of Vinyl Triflates from Enones , 1985 .

[54]  Amos B. Smith,et al.  Stereoelectronic effects in the cationic rearrangements of [4.3.2]propellanes , 1985 .

[55]  W. Scott,et al.  Palladium-catalyzed carbonylative coupling of vinyl triflates with organostannanes. A total synthesis of (.+-.)-.DELTA.9(12)-capnellene , 1984 .

[56]  L. Mander,et al.  Regioselective synthesis of β-ketoesters from lithium enolates and methyl cyanoformate , 1984 .

[57]  J. Stille,et al.  Direct conversion of organic halides to aldehydes with carbon monoxide and tin hydride catalyzed by palladium , 1983 .

[58]  F. A. Davis,et al.  Oxidation of selenides to selenoxides using 2-sulfonyloxaziridines , 1983 .

[59]  M. Varney,et al.  Stereochemistry of the Claisen rearrangement of derivatives of 5-tert-butyl-1-(hydroxymethyl)-1-cyclohexene: preferred axial attachment of the side chain , 1983 .

[60]  Y. Shimura,et al.  OPTICAL RESOLUTION OF COBALT(III) COMPLEXES via CYCLODEXTRIN INCLUSION COMPOUNDS , 1982 .

[61]  H. Reich,et al.  Selenium-stabilized carbanions. Synthesis of enals and silyl enones using 1,3-bis(phenylseleno)propene , 1982 .

[62]  V. Martín,et al.  A greatly improved procedure for ruthenium tetroxide catalyzed oxidations of organic compounds , 1981 .

[63]  D. Evans,et al.  Enantioselective aldol condensations. 2. Erythro-selective chiral aldol condensations via boron enolates , 1981 .

[64]  W. Childers,et al.  Oxidation of α,β-un saturated aldehydes , 1981 .

[65]  D. Goldsmith,et al.  Preparation of a Useful Synthon for Clerodane Antifeedant Synthesis , 1981 .

[66]  Amos B. Smith,et al.  Ruthenium Tetroxide Oxidation of Simple Ethers: A Systematic Study , 1980 .

[67]  Masaaki Suzuki,et al.  A facile procedure for acetalization under aprotic conditions , 1980 .

[68]  D. Clive.  Modern organoselenium chemistry , 1978 .

[69]  K. Sharpless,et al.  Allylic oxidation of olefins by catalytic and stoichiometric selenium dioxide with tert-butyl hydroperoxide , 1977 .

[70]  M. Nishizawa,et al.  Total synthesis of (+)-costunolide , 1977 .

[71]  R. Reuss,et al.  Synthetic methods. VIII. Hydroxylation of carbonyl compounds via silyl enol ethers , 1975 .

[72]  J. Schwartz,et al.  Hydrozirconation. Organic synthesis via organozirconium intermediates. Synthesis and rearrangement of alkylzirconium(IV) complexes and their reaction with electrophiles , 1974 .

[73]  M. Vázquez,et al.  Peracid oxidation of trimethylsilyl enol ethers: A facile α-hydroxylation procedure , 1974 .

[74]  S. Benetti,et al.  A Facile Alkylation of Ethyl 2-Oxocyclopentanecarboxylate , 1973 .

[75]  J. Fried,et al.  Total synthesis of prostaglandins. Control of regiospecificity in the alane-epoxide reaction and selective catalytic oxidation of alkynylation products , 1973 .

[76]  K. Sharpless,et al.  Selenium dioxide oxidation of olefins. Evidence for the intermediacy of allylseleninic acids , 1972 .

[77]  W. Doering,et al.  Sulfur trioxide in the oxidation of alcohols by dimethyl sulfoxide , 1967 .

[78]  R. Ireland,et al.  Allylic Rearrangements. XLI. The Reaction of Thionyl Chloride with Steroid Allylic Alcohols1 , 1958 .

[79]  W. G. Young,et al.  THE REACTION OF THIONYL CHLORIDE WITH ALLYLIC ALCOHOLS1a , 1955 .

[80]  T. Reichstein,et al.  Über Bestandteile der Nebennieren‐Rinde XV. Überführung von Cortico‐steron in Allo‐pregnan , 1938 .

[81]  H. Meerwein,et al.  Über Tertiäre Oxoniumsalze, I , 1937 .