Concise Total Synthesis of (-)-Muricatacin and (-)-iso-Cladospolide B Using Chemoselective Cross-Metathesis

Abstract

A concise total synthesis of (-)-muricatacin and (-)-iso-cladospolide B has been achieved by using chemoselective cross-metatheses and asymmetric dihydroxylations. These key reactions allow a fast access to α-hydroxybutyrolactones.

cross-coupling - metathesis - chemoselectivity - dihydroxylations - total synthesis

References and Notes

<A NAME="RG23507ST-1">1</A> Cave A. Chaboche C. Figadère B. Harmange JC. Laurens AA. Peyrat JF. Pichon M. Szlosek M. Cotte-Laffite J. Quero AM. Eur. J. Med. Chem.  1997,  617 

<A NAME="RG23507ST-2">2</A> Reiser MJ. Kozlowski JF. Wood KV. McLaughlin JL. Tetrahedron Lett.  1991,  32:  1137 

<A NAME="RG23507ST-3A">3a</A> Prasad KR. Anbarasan P. Tetrahedron: Asymmetry  2006,  17:  2465 

<A NAME="RG23507ST-3B">3b</A> Popsavin V. Krstić I. Popsavin M. Srećo B. Benedeković G. Kojić V. Bogdanović G. Tetrahedron  2006,  62:  11044 

<A NAME="RG23507ST-3C">3c</A> Popsavin V. Srećo B. Krstić I. Popsavin M. Kojić V. Bogdanović G. Eur. J. Med. Chem.  2006,  1217 

<A NAME="RG23507ST-3D">3d</A> Dhotare B. Chattopadhyay A. Tetrahedron Lett.  2005,  46:  3103 

<A NAME="RG23507ST-3E">3e</A> Quinn KJ. Isaacs AK. Arvary RA. Org. Lett.  2004,  6:  4143 

<A NAME="RG23507ST-3F">3f</A> Yoshimitsu T. Makino T. Nagaoka H. J. Org. Chem.  2003,  68:  7548 

<A NAME="RG23507ST-3G">3g</A> Bernard AM. Frongia A. Piras PP. Secci F. Org. Lett.  2003,  5:  2923 

<A NAME="RG23507ST-3H">3h</A> Popsavin V. Krstić I. Popsavin M. Tetrahedron Lett.  2003,  44:  8897 

<A NAME="RG23507ST-3I">3i</A> Raghavan S. Joseph SC. Tetrahedron: Asymmetry  2003,  14:  101 

<A NAME="RG23507ST-3J">3j</A> Carda M. Rodriguez S. Gonzalez F. Castillo E. Villanueva A. Marco JA. Eur. J. Org. Chem.  2002,  2649 

<A NAME="RG23507ST-3K">3k</A> Chandrasekhar M. Chandra KL. Singh VK. Tetrahedron Lett.  2002,  43:  2773 

<A NAME="RG23507ST-3L">3l</A> Konno H. Hiura N. Yanura M. Heterocycles  2002,  57:  1793 

<A NAME="RG23507ST-3M">3m</A> Baylon C. Prestat G. Heck MP. Mioskowski C. Tetrahedron Lett.  2000,  41:  3833 

<A NAME="RG23507ST-3N">3n</A> Trost BM. Rhee YH. J. Am. Chem. Soc.  1999,  121:  11680 

<A NAME="RG23507ST-3O">3o</A> Solladié G. Hanquet G. Izzo I. Crumbie R. Tetrahedron Lett.  1999,  40:  3071 

<A NAME="RG23507ST-3P">3p</A> Couladouros EA. Mihou AP. Tetrahedron Lett.  1999,  40:  4861 

<A NAME="RG23507ST-3Q">3q</A> Marshall JA. Welmaker GS. J. Org. Chem.  1994,  59:  4122 

<A NAME="RG23507ST-3R">3r</A> Wang Z.-M. Zhang X.-L. Sharpless KB. Tetrahedron Lett.  1992,  33:  6407 

<A NAME="RG23507ST-3S">3s</A> Scholz G. Tochtermann W. Tetrahedron Lett.  1991,  32:  5535 

<A NAME="RG23507ST-3T">3t</A> Kotsuki H. Miyazaki A. Ochi M. Slims JJ. Bull. Chem. Soc. Jpn.  1991,  64:  721 

<A NAME="RG23507ST-3U">3u</A> Wright AE. Schafer M. Midland S. Munnecke DE. Slims JJ. Tetrahedron Lett.  1989,  30:  5699 

<A NAME="RG23507ST-4A">4a</A> Smith CJ. Abbanat D. Bernan VS. Maiese WM. Greenstein M. Jompa J. Tahir A. Ireland CM. J. Nat. Prod.  2000,  63:  142 

<A NAME="RG23507ST-4B">4b</A> Brauers G. Edrada RA. Ebel R. Proksch P. Wray V. Berg A. Gräfe U. Schächtele C. Totzke F. Finkenzeller G. Marme D. Kraus J. Munchbach M. Michel M. Bringmann G. Schaumann K. J. Nat. Prod.  2000,  63:  739 

<A NAME="RG23507ST-4C">4c</A> Gestner S. Cohen N. Ilan M. Yarden O. Carmeli S. J. Nat. Prod.  2005,  68:  1350 

<A NAME="RG23507ST-4D">4d</A> Dai H.-Q. Kang Q.-J. Li G.-H. Shen Y.-M. Helv. Chim. Acta  2006,  89:  527 

<A NAME="RG23507ST-5A">5a</A> Franck X. Vaz Araujo ME. Jullian JC. Hocquemiller R. Figadère B. Tetrahedron Lett.  2001,  42:  2801 

<A NAME="RG23507ST-5B">5b</A> Austin KAB. Banwell MG. Loong DTJ. Rae D. Willis AC. Org. Biomol. Chem.  2005,  3:  1081 

<A NAME="RG23507ST-5C">5c</A> Pandey SK. Kumar P. Tetrahedron Lett.  2005,  46:  6625 

<A NAME="RG23507ST-5D">5d</A> Sharma GVM. Reddy JJ. Reddy KL. Tetrahedron Lett.  2006,  47:  6531 

<A NAME="RG23507ST-6">6</A> Sharma GVM. Reddy JJ. Reddy KL. Tetrahedron Lett.  2006,  47:  6537 

<A NAME="RG23507ST-7">7</A> Ferrié L. Amans D. Reymond S. Bellosta V. Capdevielle P. Cossy J. J. Organomet. Chem.  2006,  691:  5456 

<A NAME="RG23507ST-8A">8a</A> Kolb HC. VanNieuwenhze MS. Sharpless KB. Chem. Rev.  1994,  94:  2483 

<A NAME="RG23507ST-8B">8b</A> Xu D. Crispino GA. Sharpless KB. J. Am. Chem. Soc.  1992,  114:  1510 

<A NAME="RG23507ST-8C">8c</A> Hermitage SA. Murphy A. Nielsen P. Roberts SM. Tetrahedron  1998,  54:  13185 

<A NAME="RG23507ST-8D">8d</A> Zaitsev AB. Adolfsson H. Synthesis  2006,  1725 

<A NAME="RG23507ST-9A">9a</A> Corey EJ. Fuchs PL. Tetrahedron Lett.  1972,  36:  3769 

<A NAME="RG23507ST-9B">9b</A> Bialy L. Waldmann H. Chem. Eur. J.  2004,  10:  2759 

<A NAME="RG23507ST-10">10</A>

Compound 5 (prepared in >10 mmol scale): IR (neat): 3000-2800, 2200, 1650, 1593, 1427, 1339, 1167,1095, 995, 953, 832, 789 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.39 (dd, J = 15.0, 11.3 Hz, 1 H), 6.47 (t, J = 11.3 Hz, 1 H), 6.05 (d, J = 11.3 Hz, 1 H), 6.01 (dq, J = 15.1, 6.9 Hz, 1 H), 3.66 (s, 3 H), 3.20 (s, 3 H), 1.84 (d, J = 6.9 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.4 (br s), 143.1 (d), 139.0 (d), 128.6 (d), 113.5 (d), 61.5 (q), 32.1 (br q), 18.5 (q). MS (EI): m/z (%) = 155 (21) [M^+•], 124 (2) [M - OMe⁺], 95 (100) [M - NMeOMe⁺], 67 (60) [95 - CO⁺].

<A NAME="RG23507ST-11">11</A>

Modified AD-mix: OsO₄ (2 mol%), (DHQ)₂PHAL for AD-mix α (4 mol%), or (DHQD)₂PHAL for AD-mix β (4 mol%), MeSO₂NH₂ (1 equiv), K₃Fe(CN)₆ (3 equiv), K₂CO₃ (3 equiv), t-BuOH-H₂O, see ref. 8c.

<A NAME="RG23507ST-12">12</A>

The ee of lactone 7 was determined by chiral supercritic fluid chromatography (SFC) [Chiralcel OD-H, CO₂ 100 bar, 5 mL/min, 7% i-PrOH, λ = 220 nm, t _R (S,S) = 5.87 min, t _R (R,R) = 6.50 min].

<A NAME="RG23507ST-13">13</A>

(-)-Muricatacin (prepared in <1 mmol scale): mp 69-72 °C (synthetic product^3j mp 68-70 °C); [α]_D ²⁰ -19.6 (c 1.0, CHCl₃) {isolated natural product⁵ [α]_D ²⁰ -16.1; reported synthetic product^3j [α]_D ²³ -19.5 (c 2.1, CHCl₃)}; IR (neat): 3396, 3000-2800, 1727, 1470, 1176 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 4.41 (td, J = 7.5, 4.6 Hz, 1 H), 3.57 (m, 1 H), 2.62 (ddd, J = 17.8, 9.9, 5.0 Hz, 1 H), 2.54 (ddd, J = 17.8, 9.5, 9.0 Hz, 1 H), 2.30-2.20 (m, 1 H), 2.17-2.06 (m, 1 H), 1.88 (m, 1 H, OH), 1.60-1.18 (m, 22 H), 0.88 (t, J = 6.7 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 177.1 (s), 82.9 (d), 73.7 (d), 33.0 (t), 31.9 (t), 29.6 (t), 29.6 (t), 29.6 (t), 29.5 (t), 29.5 (t), 29.5 (t), 29.3 (t), 28.9 (t), 25.4 (t), 24.1 (t), 22.7 (t), 14.1 (q). MS (EI): m/z (%) = 283 (1) [M - H⁺], 207 (9), 97 (14), 86 (100), 69 (17), 55 (17). ESI-HRMS: m/z calcd for C₁₇H₃₂O₃ + Na⁺: 307.2244; found: 307.2239.

<A NAME="RG23507ST-14">14</A>

(-)-iso-Cladospolide B (prepared in <1 mmol scale): [α]_D ²⁰ -61.6 (c 0.50, MeOH); {isolated natural product^4c [α]_D ²⁸ -61.0 (c 16.6, MeOH)}. IR (neat): 3487, 3000-2800, 1745, 1462, 1329, 1165, 1097, 1042, 828 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.46 (dd, J = 5.8, 1.5 Hz, 1 H), 6.18 (dd, J = 5.8, 2.0 Hz, 1 H), 4.99 (dt_app, J = 4.5, 1.8 Hz, 1 H), 3.86-3.66 (m, 2 H), 2.21-1.81 (m, 2 H, OH), 1.66-1.26 (m, 10 H), 1.18 (d, J = 6.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 172.9 (s), 153.8 (d), 122.7 (d), 86.2 (d), 71.7 (d), 68.0 (d), 39.0 (t), 33.0 (t), 29.3 (t), 25.5 (t), 25.4 (t), 23.5 (q). ESI-HRMS (ESI): m/z calcd for C₁₂H₂₀O₄ + Na⁺: 251.1248; found: 251.1253.