Total Synthesis of (+)-Aculeatin
D and (+)-6-epi-Aculeatin D

J. S. Yadav; K. V. Raghavendra Rao; K. Ravindar; B. V. Subba Reddy

doi:10.1055/s-0029-1218546

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Synlett 2010(1): 51-54
DOI: 10.1055/s-0029-1218546

LETTER

Total Synthesis of (+)-Aculeatin D and (+)-6-epi-Aculeatin D

J. S. Yadav*, K. V. Raghavendra Rao, K. Ravindar, B. V. Subba Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax: +91(40)27160512; e-Mail: yadavpub@iict.res.in;

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Publication History

Received 7 September 2009
Publication Date:
09 December 2009 (online)

Abstract
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Abstract

The stereoselective total synthesis of spiroketal natural product (+)-aculeatin D and unnatural (+)-6-epi-aculeatin D has been accomplished. Sharpless kinetic resolution of secondary allylic alcohol and phenyliodine(III) bis(trifluoroacetate) (PIFA)-mediated oxidative spirocyclization were used as key steps in this synthesis.

Key words

(+)-aculeatin D - (+)-6-epi-aculeatin D - Sharpless kinetic resolution - spirocylization

References and Notes

1a Heilmann J. Mayr S. Brun R. Rali T. Sticher O. Helv. Chim. Acta 2000, 83: 2939

Search in Google Scholar
1b Heilmann J. Brun R. Mayr S. Rali T. Sticher O. Phytochemistry 2001, 57: 1281

Search in Google Scholar
2 Holdsworth KD. Mahana P. Int. J. Crude Drug Res. 1983, 21
3 For the importance of Michael acceptor moieties for cytotoxicity, see, for example: Buck SB. Hardouin C. Ichikawa S. Soenen DR. Gauss C.-M. Hwang I. Swingle MR. Bonness KM. Honkanen RE. Boger DL. J. Am. Chem. Soc. 2003, 125: 15694

Crossref Search in Google Scholar
4a Wong YS. J. Chem. Soc., Chem. Commun. 2002, 686
4b Falomir E. Alvarez-Bercedo P. Carda M. Marco JA. Tetrahedron Lett. 2005, 46: 8407

Search in Google Scholar
4c Baldwin JE. Adlington RM. Sham VWW. Marquez R. Bulger PG. Tetrahedron 2005, 61: 2353

Search in Google Scholar
4d Alvarez-Bercedo P. Falomir E. Carda M. Marco JA. Tetrahedron 2006, 62: 9641

Search in Google Scholar
4e Peuchmaur M. Wong YS. J. Org. Chem. 2007, 72: 5374

Search in Google Scholar
4f Chandrasekhar S. Rambabu C. Shyamsunder T. Tetrahedron Lett. 2007, 48: 683

Search in Google Scholar
4g Ramana CV. Srinivas B. J. Org. Chem. 2008, 73: 3915

Search in Google Scholar
4h Zhen ZB. Gao J. Wu Y. J. Org. Chem. 2008, 73: 7310

Search in Google Scholar
5 Martin VS. Woodard SS. Katsuki T. Yamada Y. Ikeda M. Sharpless KB. J. Am. Chem. Soc. 1981, 103: 6237

Crossref Search in Google Scholar
6 Sharpless KB. Behrens CH. Katsuki T. Lee AWM. Martin VS. Takatani M. Viti SM. Walker FJ. Woodard SS. Pure. Appl. Chem. 1983, 55: 589

Crossref Search in Google Scholar
7 Karsuki T. In Comprehensive Asymmetric Catalysis Vol. 2: Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 1999. p.621-648

Search in Google Scholar
8 Corey EJ. Clark DA. Goto G. Marfat A. Mioskowski C. Samuelsson B. Hammarstroem S. J. Am. Chem. Soc. 1980, 102: 1436

Crossref Search in Google Scholar
9 Galatsis P. Encyclopedia of Reagents for Organic Synthesis John Wiley & Sons; New York: 2001.
10 Chao JL. Tetrahedron 1996, 52: 5643

Crossref Search in Google Scholar
11 Tanner D. Groth T. Tetrahedron 1997, 53: 16139

Crossref Search in Google Scholar
12 Smith AB. Lee D. J. Am. Chem. Soc. 2007, 129: 10957

Crossref Search in Google Scholar
13 Bolshakov S. Leighton J. Org. Lett. 2005, 7: 3809

Crossref Search in Google Scholar
14 Omura K. Swern D. Tetrahedron 1978, 34: 1651

Crossref Search in Google Scholar
15a Deslongchamps P. Stereoelectronic Effects in Organic Chemistry Pergamon Press; Oxford: 1984.
15b Graczyk PP. Mikolajczyk M. Top. Stereochem. 1994, 21: 159

Search in Google Scholar

16

(1 R )-1-[(2 R ,3 R )-3-Tridecyloxiran-2-yl]-3-buten-1-ol (8): colorless oil; [α]_D ^²5 +5.8 (c 1.0, CHCl₃); IR (neat): 3384, 2919, 2850, 1639, 1464, 1283, 1066, 883 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 5.90-5.74 (m, 1 H), 5.18-5.08 (m, 2 H), 3.56-3.47 (m, 1 H), 2.88-2.83 (t, J = 2.2 Hz, 1 H), 2.72-2.68, (q, J = 2.2 Hz, 1 H), 2.38-2.31 (m, 2 H), 1.88 (br s, 1 H), 1.30-1.24 (m, 24 H), 0.88 (t, J = 6.6 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 133.6, 118.1, 68.1, 60.4, 55.4, 38.1, 31.9, 31.5, 29.7, 29.6 (× 2), 29.5 (× 2), 29.4, 29.3 (× 2), 25.9, 22.6, 14.1; ESI-MS: m/z = 319 [M + Na]⁺; HRMS:
m/z [M + Na]⁺ calcd for C₁₉H₃₆O₂Na: 319.2613; found: 319.2599.
(4 R ,6 R )-1-Nonadecene-4,6-diol (13): white solid; mp 83-85 ˚C, [α]_D ^²5 -10.7 (c 1.0, CHCl₃); IR (neat): 3507, 3354, 2918, 2849, 1643, 1467, 1356, 1069 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 5.86-5.74 (m, 1 H), 5.18-5.08 (m, 2 H), 3.99-3.84 (m, 2 H), 2.28-2.21 (m, 2 H), 1.59-1.56 (m, 2 H), 1.33-1.23 (m, 24 H), 0.88 (t, J = 6.5 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 134.6, 118.1, 69.2, 68.1, 42.0, 41.8, 37.4, 31.9, 29.7-29.5 (× 7), 29.3, 25.7, 22.6, 14.1; ESI-MS: m/z = 321 [M + Na]⁺; HRMS: m/z [M + Na]⁺ calcd for C₁₉H₃₈O₂Na: 321.2769; found: 321.2773. tert -Butyl({(1 R ,3 R )-3-[1-( tert -butyl)-1,1-dimethylsilyl]oxy-1-tridecyl-5-hexenyl}oxy)-dimethylsilane (7):
colorless oil; [α]_D ^²5 -15.0 (c 1.0, CHCl₃); IR (neat): 2927, 2856, 1636, 1464, 1253, 1075, 833 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 5.85-5.70 (m, 1 H), 5.07-4.98 (m, 2 H), 3.85-3.69 (m, 2 H), 2.24-2.17 (m, 2 H), 1.57-1.48 (m, 2 H), 1.33-1.22 (m, 24 H), 0.92-0.81 (m, 21 H), 0.09-0.06 (m, 12 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 135.0, 116.7, 70.1, 69.8, 45.0, 42.5, 37.8, 31.9, 30.9, 29.7 (× 6), 29.6, 29.3, 25.9 (× 6), 25.6, 25.0, 22.6, 14.1, -3.9, -4.0, -4.1, -4.3; ESI-MS: m/z = 527 [M + H]⁺; HRMS: m/z [M + H]⁺ calcd for C₃₁H₆₇O₂Si₂: 527.4679; found: 527.4668. (5 R,7 R )-1-[4-(Benzyloxy)phenyl]-5,7-di[1-( tert -butyl)-1,1-dimethylsilyl]oxy-1-icosyn-3-ol (15): colorless oil; [α]_D ^²5 +11.2 (c 1.0, CHCl₃); IR (neat): 3450, 2926, 2854, 1608, 1507, 1462, 1249 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 7.45-7.32 (m, 7 H), 6.90 (d, J = 8.8 Hz, 2 H), 5.06 (s, 2 H), 4.84 (d, J = 3.2 Hz, 1 H), 4.16 (br s, 1 H), 3.74-3.65 (m, 1 H), 2.11-1.86 (m, 3 H), 1.78-1.70 (m, 2 H), 1.33-1.21 (m, 24 H), 0.94-0.83 (m, 21 H), 0.07 (s, 6 H), 0.06 (s, 6 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 158.8, 136.6, 135.2, 133.0, 128.6 (× 2), 128.0, 127.4 (× 2), 124.9, 114.7 (× 2), 88.5, 85.0, 69.9, 69.3, 61.5, 46.1, 45.2, 37.3, 32.1, 31.9, 29.7 (× 8), 29.6, 29.3, 26.4, 25.9, 25.8, 24.9, 23.4, 22.6, 18.0, 17.9, 14.1, -3.8, -4.1 (× 2), -4.4; ESI-MS: m/z = 737 [M + H]⁺; HRMS: m/z [M + Na]⁺ calcd for C₄₅H₇₆O₄NaSi₂: 759.5054; found: 759.5068.
(5 R ,7 R )-5,7-Di[1-( tert -butyl)-1,1-dimethylsilyl]oxy-1-(4-hydroxyphenyl)icosan-3-ol (16): colorless oil; [α]_D ^²5 +8.2 (c 1.0, CHCl₃); IR (neat): 3440, 2926, 2855, 1621, 1463, 1254, 1077 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 7.05 (d, J = 8.4 Hz, 2 H), 6.74 (d, J = 8.3 Hz, 2 H), 5.40 (br s, 1 H), 3.94-3.60 (m, 3 H), 2.76-2.54 (m, 2 H), 1.80-1.51 (m, 6 H), 1.41-1.21 (m, 24 H), 0.93-0.84 (m, 21 H), 0.11 (s, 6 H), 0.04 (s, 6 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 153.7, 134.1, 129.4, 115.1, 71.7, 70.2, 70.0, 48.9, 46.4, 44.1, 39.5, 37.3, 31.9, 30.7, 29.6 (× 8), 29.3, 25.9 (× 5), 25.8, 24.9, 22.6, 18.0, 17.8, 14.1, -3.8, -4.2 (× 2), -4.4; ESI-MS: m/z = 651 [M + H]⁺; HRMS: m/z [M + Na]⁺ calcd for C₃₈H₇₄O₄NaSi₂: 673.5023; found: 673.4998. (5 S ,7 R )-5,7-Di[1-( tert -butyl)-1,1-dimethylsilyl]oxy-1-(4-hydroxyphenyl)icosan-3-one (6): colorless oil; [α]_D ^²5 +8.0 (c 1.0, CHCl₃); IR (neat): 3449, 2925, 2853, 1724 (keto), 1637, 1442, 1260, 1082 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 7.03 (d, J = 8.3 Hz, 2 H), 6.73 (d, J = 8.4 Hz, 2 H), 5.12 (br s, 1 H), 4.24-4.15 (m, 1 H), 3.69-3.62 (m, 1 H), 2.85-2.41 (m, 6 H), 1.69-1.66 (m, 2 H), 1.33-1.21 (m, 24 H), 0.90-0.86 (s, 12 H), 0.84 (s, 9 H), 0.07 (s, 12 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 208.6, 135.1, 129.4, 125.0, 115.2 (× 2), 70.0, 67.4, 51.1, 46.3, 45.7, 37.6, 32.1, 31.9, 29.6 (× 6), 29.3, 28.5, 26.3, 25.9 (× 7), 25.0, 23.4, 22.6, 14.1, -4.1, -4.2, -4.3, -4.4; ESI-MS: m/z = 649 [M + H]⁺; HRMS: m/z [M + H]⁺ calcd for C₃₈H₇₃O₄Si₂: 649.5047; found: 649.5041. Aculeatin D: colorless oil; [α]_D ^²5 +40.0 (c 1.0, CHCl₃); IR (neat): 3426, 2923, 2853, 1660 (keto), 1628, 1459, 1061, 1013 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 6.90 (dd, J = 10.5, 3.2 Hz, 1 H), 6.77 (dd, J = 10.5, 3.2 Hz, 1 H), 6.07 (dd, J = 10.0, 1.5 Hz, 1 H), 6.03 (dd, J = 10.0, 1.5 Hz, 1 H), 4.05-3.96 (m, 1 H), 3.77-3.62 (m, 1 H), 2.20 (m, 1 H), 1.97 (m, 1 H), 1.73 (m, 1 H), 1.45-1.35 (m, 2 H), 1.31-1.06 (m, 28 H), 0.81 (t, J = 6.9 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 185.6, 151.5, 149.2, 127.0, 126.8, 108.9, 82.8, 69.0, 68.1, 43.9, 42.8, 35.8, 34.5, 32.1, 31.9, 30.3, 29.8-29.5 (× 4), 29.3, 28.9, 28.8, 28.5, 25.7, 21.7; ESI-MS: m/z = 419 [M + H]⁺, 441 [M + Na]⁺; HRMS: m/z [M + Na]⁺ calcd for C₂₆H₄₂O₄Na: 441.2980; found: 441.2970. 6- epi -Aculeatin D: colorless oil; [α]_D ^²5 +5.0 (c 1.0, CHCl₃); IR (neat): 3426, 2923, 2853, 1660 (keto) cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 6.77 (dd, J = 10.5, 3.2 Hz, 1 H), 6.72 (dd, J = 10.5, 3.2 Hz, 1 H), 6.06 (dd, J = 10.0, 1.9 Hz, 1 H), 6.03 (dd, J = 10.0, 1.9 Hz, 1 H), 4.04-3.90 (m, 1 H), 3.75-3.67 (m, 1 H), 2.37-2.15 (m, 3 H), 2.01-1.93 (m, 3 H), 1.86-1.56 (m, 3 H), 1.35-1.15 (m, 24 H), 0.83 (t, J = 7.3 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 185.3, 151.4, 149.8, 128.7, 128.6, 109.6, 79.5, 68.1, 63.9, 41.4, 40.5, 38.7, 35.8, 34.6, 31.9, 30.3, 29.6 (× 4), 29.5, 29.3, 28.9, 23.7, 22.9, 14.0; ESI-MS: m/z = 419 [M + H]⁺.