Summary of the Synthesis and Elaboration of the Three Core

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References

(1) Schinzer, D.; Schulz, C.; Krug, O. "Studies toward the total synthesis of sorangicins: Asymmetric synthesis of the key fragments." Synlett 2004, 2689- 2692.

(2) Smith, A. B.; Dong, S. Z. "An Efficient, Second-Generation Synthesis of the Signature Dioxabicyclo[3.2.1]octane Core of (+)-Sorangicin A and Elaboration of the (Z,Z,E)-Triene Acid System." Org Lett 2009, 11, 1099-1102.

(3) Smith, A. B.; Fox, R. J. "Construction of a C(30-38) dioxabicyclo[3.2.1]octane subtarget for (+)-sorangicin A, exploiting a regio- and stereocontrolled acid-catalyzed epoxide ring opening." Org Lett 2004, 6, 1477- 1480.

(4) Smith, A. B.; Fox, R. J.; Vanecko, J. A. "(+)-sorangicin A synthetic studies. Construction of the C(1-15) and C(16-29) subtargets." Org Lett 2005, 7, 3099- 3102.

(5) Jansen, R.; Schummer, D.; Irschik, H.; Hofle, G. "Antibiotics from Gliding Bacteria .47. Chemical Modification of Sorangicin-a and Structure Activity Relationship .1. Carboxyl and Hydroxyl Group Derivatives." Liebigs Ann Chem 1990, 975-988.

(6) Tortosa, M.; Yakelis, N. A.; Roush, W. R. "Total synthesis of (+)- Superstolide A." J Am Chem Soc 2008, 130, 2722-+.

(7) Parenty, A.; Moreau, X.; Campagne, J. M. "Macrolactonizations in the total synthesis of natural products." Chem Rev 2006, 106, 911-939.

(8) Sabitha, G.; Reddy, E. V.; Bhikshapathi, M.; Yadav, J. S. "Total synthesis of (9S,12R,13S)-pinellic acid." Tetrahedron Lett 2007, 48, 313-315.

(9) Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira, E. M. "The discovery of novel reactivity in the development of C-C bond-forming reactions: In situ generation of zinc acetylides with Zn-II/R3N." Accounts Chem Res 2000, 33, 373-381.

(10) Ramachandran, P. V.; Srivastava, A.; Hazra, D. "Total synthesis of potential antitumor agent, (-)-dictyostatin." Org Lett 2007, 9, 157-160.

(11) Namba, K.; Cui, S.; Wang, J. S.; Kishi, Y. "A new method for translating the asymmetric Ni/Cr-mediated coupling reactions from stoichiometric to catalytic." Org Lett 2005, 7, 5417-5419.

65

(12) Chatterjee, A. K.; Choi, T. L.; Sanders, D. P.; Grubbs, R. H. "A general model for selectivity in olefin cross metathesis." J Am Chem Soc 2003, 125, 11360-11370.

(13) Blakemore, P. R. "The modified Julia olefination: alkene synthesis via the condensation of metallated heteroarylalkylsulfones with carbonyl compounds." J Chem Soc Perk T 1 2002, 2563-2585.

(14) Fukuyama, T.; Vranesic, B.; Negri, D. P.; Kishi, Y. "Synthetic Studies on Polyether Antibiotics .2. Stereocontrolled Syntheses of Epoxides of Bis- Homoallylic Alcohols." Tetrahedron Lett 1978, 2741-2744.

(15) Christmann, M.; Bhatt, U.; Quitschalle, M.; Claus, E.; Kalesse, M. "Total synthesis of (+)-ratjadone." Angew Chem Int Edit 2000, 39, 4364-+.

(16) Vilotijevic, I.; Jamison, T. F. "Epoxide-opening cascades promoted by water." Science 2007, 317, 1189-1192.

(17) Zhen, Z. B.; Gao, J.; Wu, Y. "A chiron approach to the total synthesis of (+)-aculeatin D." J Org Chem 2008, 73, 7310-7316.

(18) Evans, D. A.; Downey, C. W.; Shaw, J. T.; Tedrow, J. S. "Magnesium halide-catalyzed anti-aldol reactions of chiral N-acylthiazolidinethiones." Org Lett 2002, 4, 1127-1130.

(19) Crimmins, M. T.; Christie, H. S.; Chaudhary, K.; Long, A. "Enantioselective synthesis of apoptolidinone: Exploiting the versatility of thiazolidinethione chiral auxiliaries." J Am Chem Soc 2005, 127, 13810-13812.

(20) Uday, R. S.; Brown, H. C. "Chiral Synthesis via Organoboranes. 27. Remarkably Rapid and Exceptionally Enantioselective (approaching 100% ee) Allylboration of Representative Aldehydes at -100° Under New, Salt-Free Conditions." J Org Chem 1991, 56, 401-404.

(21) Corey, E. J.; Hopkins, P. B.; Kim, S.; Yoo, S.; Nambiar, K. P.; Falck, J. R. "Total Synthesis of Erythromycins .5. Total Synthesis of Erythronolide-A." J Am Chem Soc 1979, 101, 7131-7134.

(22) Hill, J. G.; Sharpless, K. B.; Exon, C. M.; Regenye, R. "Enantioselective Epoxidation of Allylic Alcohols: (2S,3S)-3-Propyloxiranemethanol." Organic Syntheses 1990, 7, 461-467.

(23) Wang, C.; Rath, N. P.; Covey, D. F. "Neurosteroid analogues. Part 13: Synthetic methods for the preparation of 2 beta-hydroxygonane derivatives as structural mimics of ent-3 alpha-hydroxysteroid modulators of GABA(A) receptors." Tetrahedron 2007, 63, 7977-7984.

66

(24) Crimmins, M. T.; DeBaillie, A. C. "Enantioselective total synthesis of bistramide A." J Am Chem Soc 2006, 128, 4936-4937.

(25) Crimmins, M. T.; Caussanel, F. "Enantioselective total synthesis of FD- 891." J Am Chem Soc 2006, 128, 3128-3129.

(26) Crimmins, M. T.; Haley, M. W. "Synthesis of the C29-C37 bicyclic ether core of (+)-sorangicin A." Org Lett 2006, 8, 4223-4225.

(27) Rodriguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J. J. "Selective oxidation of primary silyl ethers and its application to the synthesis of natural products." Tetrahedron Lett 1999, 40, 5161-5164.

(28) Takai, K.; Nitta, K.; Utimoto, K. "Simple and Selective Method for Rcho- ](E)-Rch=Chx Conversion by Means of a Chx3-Crcl2 System." J Am Chem Soc 1986, 108, 7408-7410.

(29) Layton, M. E.; Morales, C. A.; Shair, M. D. "Biomimetic synthesis of (-)- longithorone A." J Am Chem Soc 2002, 124, 773-775.

(30) Cherest, M.; Felkin, H.; Prudent, N. "Torsional Strain Involving Partial Bonds . Stereochemistry of Lithium Aluminium Hydride Reduction of Some Simple Open-Chain Ketones." Tetrahedron Lett 1968, 2199-&.

(31) Nicolaou, K. C.; Jung, J.; Yoon, W. H.; Fong, K. C.; Choi, H. S.; He, Y.; Zhong, Y. L.; Baran, P. S. "Total synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 1. Racemic and asymmetric synthesis of bicyclo[4.3.1] key building blocks." J Am Chem Soc 2002, 124, 2183-2189.

(32) Krumper, J. R.; Salamant, W. A.; Woerpel, K. A. "Continuum of Mechanisms for Nucleophilic Substitutions of Cyclic Acetals." Org Lett 2008, 10, 4907-4910.

(33) Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. "Synthesis of functionalized olefins by cross and ring-closing metatheses." J Am Chem Soc 2000, 122, 3783-3784.

(34) Cresp, T. M.; Sondheimer, F. "4,9,16,21-Tetramethyl-5,7,17,19- Tetrakisdehydro[14]-Annuleno[14]Annulene, a Macrocyclic Analog of Naphthalene." J Am Chem Soc 1975, 97, 4412-4413.

(35) Brown, H. C.; Jadhav, P. K.; Bhat, K. S. "Chiral Synthesis Via Organoboranes .13. A Highly Diastereoselective and Enantioselective Addition of [(Z)-Gamma-Alkoxyallyl]Diisopinocampheylboranes to Aldehydes." J Am Chem Soc 1988, 110, 1535-1538.

67

(36) Ahmed, A.; Hoegenauer, E. K.; Enev, V. A. S.; Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J. "Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of sharpless' asymmetric epoxidation." J Org Chem 2003, 68, 3026-3042.

(37) Romero, J. A. C.; Tabacco, S. A.; Woerpel, K. A. "Stereochemical reversal of nucleophilic substitution reactions depending upon substituent: Reactions of heteroatom-substituted six-membered-ring oxocarbenium ions through pseudoaxial conformers." J Am Chem Soc 2000, 122, 168-169.

(38) Lindlar, H.; Dubuis, R. "Palladium Catalyst for Partial Reduction of Acetylenes." Organic Syntheses 1973, 5, 880.

(39) Shen, R. C.; Inoue, T.; Forgac, M.; Porco, J. A. "Synthesis of photoactivatable acyclic analogues of the lobatamides." J Org Chem 2005, 70, 3686-3692.

(40) Elson, K. E.; Jenkins, I. D.; Loughlin, W. A. "The Hendrickson reagent and the Mitsunobu reaction: a mechanistic study." Org Biomol Chem 2003, 1, 2958- 2965.

(41) Mikolajczyk, M.; Kielbasinski, P. "Recent Developments in the Carbodiimide Chemistry." Tetrahedron 1981, 37, 233-284.

(42) Dess, D. B.; Martin, J. C. "Readily Accessible 12-I-5 Oxidant for the Conversion of Primary and Secondary Alcohols to Aldehydes and Ketones." J Org Chem 1983, 48, 4155-4156.

(43) Bal, B. S.; Childers, W. E.; Pinnick, H. W. "Oxidation of Alpha,Beta- Unsaturated Aldehydes." Tetrahedron 1981, 37, 2091-2096.

(44) Mathias, L. J. "Esterification and Alkylation Reactions Employing Isoureas." Synthesis-Stuttgart 1979, 561-576.

(45) Franci, X.; Martina, S. L. X.; McGrady, J. E.; Webb, M. R.; Donald, C.; Taylor, R. J. K. "A comparison of the Still-Gennari and Ando HWE-methodologies with alpha,beta-unsaturated aldehydes; unexpected results with stannyl substituted systems." Tetrahedron Lett 2003, 44, 7735-7740.

C

T

C

S

3.1Synthetic Strategy

As stated in the previous chapter our synthetic approach for the synthesis of (+)-sorangicin A involved investigation of coupling strategies using dissimilar types of chemistry, all of which are accessible from the same three core fragments (Scheme 3.1). As we intended to couple the three fragments with possible bond formations in differing locations throughout the molecule, two general strategies for the synthesis of the natural product emerged and are outlined in Scheme 3.1. We envisioned the first coupling event involving the union of the bicyclic ether moiety 186 with the tetrahydropyran subunit 187 utilizing either a cross metathesis1 or a Julia-Kocienski olefination.2 From this point the strategies diverged. The first, following Path A, would investigate coupling a dihydropyran 189 to the tetrahydropyran portion of polycycle 188 forming one of three different bonds; the C20-C21 σ bond, the C19-C20 double bond, or the C15-C16 double bond. Should one of these couplings prove effective in providing the late-stage intermediate 190, macrocycle formation would follow via one of two cyclizations; 1) a Stille or a Suzuki-Miyaura

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coupling reaction3 to form the C38-C39 sigma bond, the C40-C41 sigma bond, or both in a double bond forming event, or 2) a lactonization4 between the C10 alcohol and the C43 carbonyl.