Stereoselective Synthesis of C1-C18 Region of Palmerolide A from Tartaric Acid

Abstract

A stereoselective synthesis of the C1-C18 region of marine natural product palmerolide A from chiral pool tartaric acid is presented. The key synthetic sequence includes the elaboration of a γ-oxo-amide derived from tartaric acid and alkene formation involving Boord type fragmentation.

Key words

Palmerolide A - marine natural product - stereoselective synthesis - tartaric acid

References and Notes

• 1a Diyabalanage T. Amsler CD. McClintock JB. Baker BJ. J. Am. Chem. Soc.  2006,  128:  5630 
• 1b Lebar MD. Baker BJ. Tetrahedron Lett.  2007,  48:  8009 
• 2a Jiang X. Liu B. Lebreton S. De Brabander JK.
  J. Am. Chem. Soc.  2007,  129:  6386 
• 2b Nicolaou KC. Guduru R. Sun YP. Banerji B. Chen DYK. Angew. Chem. Int. Ed.  2007,  46:  5896 
• 2c Penner M. Rauniyar V. Kaspar LT. Hall DG. J. Am. Chem. Soc.  2009,  131:  14216 
• 2d Nicolaou KC. Leung YCG. Dethe DH. Guduru R. Sun YP. Lim CS. Chen DYK. J. Am. Chem. Soc.  2008,  130:  10019 
• Formal synthesis:
• 2e Jägel J. Maier ME. Synthesis  2009,  2881 
• 2f Jones DM. Dudley GB. Synlett  2010,  223 
• 2g Lebar MD. Baker BJ. Tetrahedron  2010,  66:  1557 
• 2h Kaliappan KP. Gowrisankar P. Synlett  2007,  1537 
• 2i Cantagrel G. Meyer C. Cossy J. Synlett  2007,  2983 
• 2j Chandrasekhar S. Vijeender K. Chandrasekhar G. Reddy CR. Tetrahedron: Asymmetry  2007,  18:  2473 
• 2k Jägel J. Schmauder A. Binanzer M. Maier ME. Tetrahedron  2007,  63:  13006 
• 3a For a general approach to the synthesis of g-keto amides from tartaric acid, see: Prasad KR. Chandrakumar A. Tetrahedron  2007,  63:  1798 
• For recent application of γ-keto amides derived from tartaric acid in natural product synthesis, see:
• 3b Prasad KR. Gandi VR. Synlett  2009,  2593 
• 3c Prasad KR. Gholap SL. J. Org. Chem.  2008,  73:  2 
• 3d Prasad KR. Gholap SL. J. Org. Chem.  2008,  73:  2916 
• 3e Prasad KR. Swain B. Tetrahedron: Asymmetry  2008,  19:  1134 
• 3f Prasad KR. Gandi V. Tetrahedron: Asymmetry  2008,  19:  2616 
• 3g Prasad KR. Chandrakumar A. J. Org. Chem.  2007,  72:  6312 
• 3h Prasad KR. Dhaware M. Synthesis  2007,  3697 
• 3i Prasad KR. Gholap SL. J. Org. Chem.  2006,  71:  3643 
• 3j Prasad KR. Anbarasan P. Tetrahedron Lett.  2006,  47:  1433 
• 3k Prasad KR. Anbarasan P. Tetrahedron: Asymmetry  2006,  17:  850 
• 3l Prasad KR. Anbarasan P. Tetrahedron  2006,  62:  8303 
• 3m Prasad KR. Anbarasan P. Synlett  2006,  2087 
• 4 Mukai C. Sonobe H. Kim JS. Hanaoka M. J. Org. Chem.  2000,  65:  6654 
• 5a Swallen LC. Boord CE. J. Am. Chem. Soc.  1930,  52:  651 
• For application of this strategy in the synthesis of allylic alcohols, see:
• 5b Schneider C. Kazmaier U. Synthesis  1998,  1314 
• 5c Ramarao AV. Reddy ER. Joshi BV. Yadav JS. Tetrahedron Lett.  1987,  28:  6497 
• 6a Nugiel DA. Jakobs K. Worley T. Patel M. Kaltenbach RF. Meyer DT. Jadhav PK. De Lucca GV. Smyser TE. Klabe RM. Bacheler LT. Rayner MM. Seitz SP. J. Med. Chem.  1996,  39:  2156 
• 6b McNulty J. Grunner V. Mao J. Tetrahedron Lett.  2001,  42:  5609 

7

Formation of a minor amount (5%) of diketone resulting from the addition of Grignard reagent to both amide groups was observed

8

Formation of the other diasteromer was not observed within detectable limits by ^¹H NMR

9

All new compounds exhibited satisfactory spectroscopic data. Compound 9: [α]_D -23 (c 0.5, CHCl₃); IR (neat): 3483, 2985, 1718, 1653, 1399 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 6.89 (dt, J = 15.2, 6.6 Hz, 1 H), 5.78 (dt, J = 15.6, 6.6 Hz, 1 H), 4.12 (q, J = 6.9 Hz, 2 H), 3.90-3.60 (m, 3 H), 3.54 (dd, J = 11.6, 4.6 Hz, 1 H), 2.37-2.28 (br s, 1 H), 2.27-2.12 (m, 2 H), 1.64-1.44 (m, 4 H), 1.35 (s, 3 H), 1.34 (s, 3 H), 1.23 (t, J = 6.9 Hz, 3 H); ^¹³C NMR (100 MHz, CDCl₃): δ = 166.6, 148.4, 121.7, 108.6, 81.3, 76.5, 61.8, 60.1, 32.3, 31.9, 27.3, 26.9, 24.4, 14.2; HRMS: m/z calcd for C₁₄H₂₄O₅Na: 295.1521; found: 295.1519. Compound 11: [α]_D +4.0 (c 1.0, CHCl₃); IR (neat): 3441, 2982, 1721, 1652, 1369 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 6.95 (dt, J = 15.6, 6.8 Hz, 1 H), 5.95-5.75 (m, 2 H), 5.23 (d, J = 17.2 Hz, 1 H), 5.12 (d, J = 10.4 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H), 4.11 (q, J = 6.0 Hz, 1 H), 2.24 (q, J = 6.0 Hz, 2 H), 1.75-1.62 (br s, 1 H), 1.60-1.43 (m, 4 H), 1.29 (t, J = 7.1 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 166.7, 148.8, 140.9, 121.6, 114.9, 72.9, 60.2, 36.2, 31.9, 23.7, 14.2; HRMS: m/z calcd for C₁₁H₁₈O₃Na: 221.1154; found: 221.1153. Compound 15: [α]_D +9.4 (c 2.0, CHCl₃); IR (neat): 3079, 2932, 1674, 1382, 1256 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 5.75 (ddt, J = 16.5, 10.2, 6.3 Hz, 1 H), 5.03-4.83 (m, 2 H), 4.68-4.62 (m, 1 H), 4.54-4.48 (m, 1 H), 3.84-3.70 (m, 1 H), 3.67 (s, 3 H), 3.14 (s, 3 H), 2.24-1.96 (m, 2 H), 1.72-1.55 (m, 1 H), 1.52-1.40 (m, 1 H), 1.38 (s, 3 H), 1.36 (s, 3 H), 0.80 (s, 9 H), 0.01 (s, 6 H); ^¹³C NMR (100 MHz, CDCl₃): δ = 170.4, 138.4, 114.6, 111.0, 80.0, 72.3, 71.5, 61.8, 32.2, 31.9, 29.8, 27.0, 26.2, 25.8, 18.1, -4.5, -4.6; HRMS: m/z calcd for C₁₉H₃₇NO₆SiNa: 410.2339; found: 410.2350. Compound 17: [α]_D -6.0 (c 1.0, CHCl₃); IR (neat): 3469, 2950, 1723, 1657, 1464, 1370 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 6.86 (dt, J = 15.3, 6.6 Hz, 1 H), 5.73 (d, J = 15.9 Hz, 1 H), 4.08 (q, J = 7.2 Hz, 2 H), 4.00-3.87 (m, 1 H), 3.82-3.53 (m, 4 H), 2.38 (br s, 1 H), 2.37-2.04 (m, 2 H), 1.79-1.62 (m, 1 H), 1.58-1.40 (m, 1 H), 1.30 (s, 3 H), 1.29 (s, 3 H), 1.18 (t, J = 7.2 Hz, 3 H), 0.80 (s, 9 H), 0.10 (s, 6 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 166.5, 148.3, 121.6, 108.8, 79.8, 77.1, 71.4, 62.8, 60.1, 31.1, 28.5, 27.0, 25.8, 18.1, 14.2, -4.2, -4.7; HRMS: m/z calcd for C₂₀H₃₈O₆SiNa: 425.2335; found: 425.2333. Compound 19: [α]_D +15.1 (c 1.8, CHCl₃); IR (neat): 3445, 2925, 2854, 1464, 1256 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 5.85-5.55 (m, 2 H), 5.32-5.20 (m, 2 H), 4.64 (d, J = 6.6 Hz, 1 H), 4.58 (d, J = 6.6 Hz, 1 H), 4.07 (br d, J = 4.5 Hz, 1 H), 4.02-3.93 (m, 1 H), 3.78-3.63 (m, 1 H), 3.36 (s, 3 H), 2.28-1.92 (m, 2 H), 1.73-1.55 (m, 2 H), 1.53-1.33 (m, 1 H), 0.89 (s, 9 H), 0.08 (s, 3 H), 0.06 (s, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 134.7, 133.1, 129.0, 118.0, 96.6, 79.9, 73.1, 63.8, 55.5, 32.0, 28.2, 25.9, 18.1, -4.2, -4.6; HRMS: m/z calcd for C₁₇H₃₄O₄SiNa: 353.2124; found: 353.2122. Compound 21: [α]_D +21.0 (c 0.8, CHCl₃); IR (neat): 3401, 2953, 1678, 1255, 1036 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 6.26 (dd, J = 15.0, 10.9 Hz, 1 H), 6.01 (d, J = 10.8 Hz, 1 H), 5.80 (ddd, J = 17.2, 10.5, 6.6 Hz, 1 H), 5.69 (dt, J = 15.0, 6.8 Hz, 1 H), 5.32-5.23 (m, 2 H), 4.68 (d, J = 6.6 Hz, 1 H), 4.60 (d, J = 6.6 Hz, 1 H), 4.05 (br s, 2 H), 4.04-3.96 (m, 1 H), 3.73 (dt, J = 8.2, 4.0 Hz, 1 H), 3.37 (s, 3 H), 2.30-2.06 (m, 2 H), 1.78 (s, 3 H), 1.70-1.62 (m, 1 H), 1.54-1.40 (m, 1 H), 0.9 (s, 9 H), 0.1 (s, 6 H); ^¹³C NMR (100 MHz, CDCl₃): δ = 134.8, 134.7, 134.6, 126.0, 125.2, 118.0, 94.6, 79.8, 73.6, 68.7, 55.5, 32.1, 28.9, 25.9, 18.2, 14.1, -4.2, -4.6; HRMS: m/z calcd for C₂₀H₃₈O₄SiNa: 393.2437; found: 393.2423.