Stereoselective Total Synthesis
of (-)-Ovalicin

J. S. Yadav; P. Narayana Reddy; B. V. Subba Reddy

doi:10.1055/s-0029-1219191

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Synlett 2010(3): 457-461
DOI: 10.1055/s-0029-1219191

LETTER

Stereoselective Total Synthesis of (-)-Ovalicin

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

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Publikationsverlauf

Received 28 August 2009
Publikationsdatum:
11. Januar 2010 (online)

Abstract
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Abstract

A new synthetic route for epoxyketone 3 is described, which is a key intermediate in Barton’s synthesis of ovalicin (1), a powerful anti-angiogenetic inhibitor, from commercially available d-ribose. The key reactions involved in this synthesis are ring-closing metathesis, Rubottom oxidation and Corey-Chaykovsky epoxidation. The subsequent transformations are carried out according to Barton’s strategy to complete the total synthesis of (-)-ovalicin.

Keywords

ribose - Rubottom oxidation - ring-closing metathesis - Corey-Chaykovsky epoxidation

References and Notes

1a Sigg HP. Weber HP. Helv. Chim. Acta 1968, 51: 1395

Suche in Google Scholar
1b Bollinger P. Sigg HP. Weber HP. Helv. Chim. Acta 1973, 56: 819

Suche in Google Scholar
2 Griffith EC. Su Z. Niwayama S. Ramsay CA. Chang Y.-H. Liu JO. Proc. Natl. Acad. Sci. U.S.A. 1998, 95: 15183

Crossref PubMed Suche in Google Scholar
3 Zimmermann WA. Hartmann GR. Eur. J. Biochem. 1981, 118: 143

Crossref PubMed Suche in Google Scholar
4 Ingber D. Fujita T. Kishimoto S. Sudo K. Kanamaru T. Brem H. Folkman J. Nature (London) 1990, 348: 555

Crossref PubMed Suche in Google Scholar
5 Borel JF. Lazary S. Staehelin H. Agents Actions 1974, 4: 357

Crossref PubMed Suche in Google Scholar
6a Corey EJ. Dittami JP. J. Am. Chem. Soc. 1985, 107: 256

Suche in Google Scholar
6b Corey EJ. Guzman-Perez A. Noe MC. J. Am. Chem. Soc. 1994, 116: 12109

Suche in Google Scholar
6c Barton DHR. Bath S. Billington DD. Gero SD. Quiclet-Sire B. Samadi M. Org. Bioorg. Chem. 1995, 12: 1551

Suche in Google Scholar
6d Barco A. Benetti S. De Risi C. Marchetti P. Pollini GP. Zanirato V. Tetrahedron: Asymmetry 1998, 9: 2857

Suche in Google Scholar
7a Yamaguchi J. Toyoshima M. Shoji M. Kakeya H. Osada H. Hayashi Y. Angew. Chem. Int. Ed. 2006, 45: 789

Suche in Google Scholar
7b Takahashi S. Hishinuma N. Koshino H. Nakata T. J. Org. Chem. 2005, 70: 10162

Suche in Google Scholar
7c Tiefenbacher K. Arion VB. Mulzer J. Angew. Chem. Int. Ed. 2007, 46: 2690

Suche in Google Scholar
7d Yadav JS. Sreedhar P. Dinesh CB. Srihari P. Synlett 2007, 992
7e Hua H. Zhao H. Battina K. Lou K. Jimenez L. Desper J. Perchellet M. Perchellet H. Chaiang K. Bioorg. Med. Chem. 2008, 16: 5232

Suche in Google Scholar
8 Leonard NJ. Carraway KL. J. Heterocycl. Chem. 1966, 3: 485

Crossref Suche in Google Scholar
9 Garegg PJ. Samuelson B. J. Chem. Soc., Perkin Trans. 1 1980, 2866

Crossref
10 Hyldtoft L. Madsen R. J. Am. Chem. Soc. 2000, 122: 8444

Crossref Suche in Google Scholar
11a Armstrong SK. J. Chem. Soc., Perkin Trans. 1 1998, 371
11b Grubbs RH. Chang S. Tetrahedron 1998, 54: 4413

Suche in Google Scholar
11c Schuster M. Blechert S. Angew. Chem., Int. Ed. Engl. 1997, 36: 2036

Suche in Google Scholar
11d Furstner A. Angew. Chem. Int. Ed. 2000, 39: 3013

Suche in Google Scholar
12a Rubottom GM. Vazquez MA. Pellagrina DR. Tetrahedron Lett. 1974, 4319
12b Rubottom GM. Gruber JM. Juve HD. Charleson DA. Org. Synth. 1986, 64: 118

Suche in Google Scholar
12c Hassner A. Reuss RH. Pinnick HW. J. Org. Chem. 1975, 40: 3427

Suche in Google Scholar
12d Brook AG. Macrae DM. J. Organomet. Chem. 1974, 77: C19

Suche in Google Scholar
13 Corey EJ. Kang J. Kyler K. Tetrahedron Lett. 1985, 26: 555

Crossref Suche in Google Scholar
14 Pine SH. Shen GS. Hoang H. Synthesis 1991, 165

Thieme Connect
15 Yan T.-H. Tsai C.-C. Chien C.-T. Cho C.-C. Huang P.-C. Org. Lett. 2004, 6: 4961

Crossref PubMed Suche in Google Scholar
16a Corey EJ. Chakovsky M. J. Am. Chem. Soc. 1965, 87: 1353

Suche in Google Scholar
16b Harwood LM. Casy G. Sherlock J. Synth. Commun. 1990, 1287
17a Rodeschini V. Boiteau JG. Weghe PV. Tarnus C. Eustache J. J. Org. Chem. 2004, 69: 357

Suche in Google Scholar
17b Boiteau JG. Weghe PV. Eustache J. Org. Lett. 2001, 3: 2737

Suche in Google Scholar
17c Mazitschek R. Huwe A. Giannis A. Org. Biomol. Chem. 2005, 3: 2150

Suche in Google Scholar
17d Tabber DF. Christos TE. Rheingold AL. Guzei A. J. Am. Chem. Soc. 1999, 121: 5589

Suche in Google Scholar
18a Kishi Y. Fukuyama T. Natatsuka S. J. Am. Chem. Soc. 1973, 95: 6490

Suche in Google Scholar
18b Fukuyama T. Natatsuka S. Kishi Y. Tetrahedron 1981, 37: 2045

Suche in Google Scholar
18c Wu Z. Williams LJ. Danishefsky SJ. Angew. Chem. 2000, 39: 3866

Suche in Google Scholar
18d Smith AB. Dorsey BD. Visnick M. Maeda T. Malamas MS. J. Am. Chem. Soc. 1986, 108: 3110

Suche in Google Scholar

19

Spectroscopic Data for Selected Products:
(3a S ,7a R )-2,2-Dimethyl-3a,4,5,7a-tetrahydro-1,3-benzodioxol-4-ol (8): major isomer, brown solid; mp 88-
90 ˚C; [α]_D -18.1 (c = 1, CHCl₃). IR (neat): 3440, 2923, 1648, 1373, 1075 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.37 (s, 3 H), 1.40 (s, 3 H), 1.96 (d, J = 8.7 Hz, 1 H), 2.25 (m, 2 H), 3.83 (m, 1 H), 4.34 (m, 1 H), 4.56 (s, 1 H), 5.69 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 126.6, 126.0, 109.4, 76.1, 73.4, 67.1, 28.7, 27.3, 26.3. MS (ESI): m/z = 193 [M + Na]⁺.
(3a S ,7a R )-2,2-Dimethylperhydro-1,3-benzodioxol-4-ol (9): mixture of isomers, yellow oil; [α]_D -26.6 (c = 1, CHCl₃). IR (neat): 3446, 2937, 1376, 1032, 876 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.35 (s, 3 H), 1.50 (s, 3 H), 1.54-1.80 (m, 6 H), 2.07 (s, 1 H), 3.68-3.76 (m, 1 H), 4.14-4.22 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 108.5, 81.5, 75.7, 74.4, 72.6, 68.2, 30.4, 28.3, 27.6, 27.5, 27.0, 26.7, 26.2, 25.6, 18.6, 17.4. MS (ESI): m/z = 195 [M + Na]⁺.
(3a R,7a R )-2,2-Dimethylperhydro-1,3-benzodioxol-4-one (10): white solid; mp 112-114 ˚C; [α]_D -63.2 (c = 1, CHCl₃). IR (neat): 3447, 2937, 1726, 1376, 1220 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 1.36 (s, 3 H), 1.41 (s, 3 H), 1.82-2.06 (m, 3 H), 2.14-2.38 (m, 2 H), 2.43-2.56 (m, 1 H), 4.22 (d, J = 5.4 Hz, 1 H), 4.53-4.61 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 208.4, 109.4, 79.1, 39.9, 26.9, 26.7, 25.8, 20.2, 17.4. MS (ESI): m/z = 171 [M + H]⁺.
(3a R ,5 R ,7a R )-5-[1-( tert -Butyl)-1,1-diphenylsilyl]oxy-2,2-dimethylperhydro-1,3-benzodioxol-4-one (13): colorless liquid; [α]_D -62.4 (c = 1.7, CHCl₃). ^¹H NMR (300 MHz, CDCl₃): δ = 1.08 (s, 9 H), 1.36 (s, 3 H), 1.37 (s, 3 H), 1.73-1.92 (m, 2 H), 1.95-2.05 (m, 1 H), 2.41-2.55 (m, 1 H), 4.18 (dd, J = 2.2, 3.7 Hz, 1 H), 4.61 (m, 1 H), 4.82 (d, J = 5.2 Hz, 1 H), 7.31-7.46 (m, 6 H), 7.50-7.54 (m, 2 H), 7.58-7.62 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 206.4, 135.5, 135.4, 134.7, 132.9, 130.1, 129.5, 127.8, 127.6, 109.6, 78.5, 77.8, 76.3, 29.2, 26.9, 26.8, 26.5, 26.1, 20.6. MS (ESI): m/z = 447 [M + Na]⁺.
(7 R ,8 R ,11 R )-11-[1-( tert -Butyl)-1,1-diphenylsilyl]oxy-1,5-dithiaspiro[5.5]undecane-7,8-diol (14): semi solid; [α]_D +16.7 (c = 1.3, CHCl₃). IR (neat): 3446, 2925, 2854, 1109, 702 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 1.09 (s, 9 H), 1.32-2.16 (m, 7 H), 2.56-2.70 (m, 1 H), 2.75-2.89 (m, 2 H), 2.92-3.11 (m, 2 H), 3.91 (dd, J = 3.8 Hz, 1 H), 4.08-4.22 (m, 2 H), 7.28-7.47 (m, 6 H), 7.65-7.81 (m, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 136.5, 135.5, 132.7, 132.2, 130.1, 129.6, 127.8, 127.4, 75.0, 74.4, 73.1, 29.6, 29.2, 27.2, 26.8, 23.3, 19.2. MS (ESI): m/z = 497 [M + Na]⁺.
(7 R ,8 R ,11 R )-7-(Acetyloxy)-11-[1-( tert -butyl)-1,1-diphenylsilyl]oxy-1,5-dithiaspiro[5.5]undec-8-yl Acetate (15): semi solid; [α]_D +25.2 (c = 1, MeOH). IR (neat): 3451, 2929, 2856, 1743, 1245, 703 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.10 (s, 9 H), 1.24-1.61 (m, 5 H), 1.93 (s, 3 H), 1.96 (s, 3 H), 2.02-2.16 (m, 1 H), 2.50-2.60 (m, 1 H), 2.74-2.84 (m, 1 H), 2.98-3.10 (m, 1 H), 3.14-3.26 (m, 1 H), 3.88 (dd, J = 4.5, 12.0 Hz, 1 H), 5.53-5.62 (m, 1 H), 5.77 (d, J = 1.5 Hz, 1 H), 7.31-7.41 (m, 6 H), 7.68-7.73 (m, 2 H), 7.76-7.81 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 136.3, 136.0, 135.2, 134.7, 129.6, 129.4, 127.5, 127.3, 73.4, 69.1, 60.5, 26.9, 26.5, 25.6, 24.8, 23.5, 20.8, 20.6, 19.6, 18.9. MS (ESI): m/z = 581 [M + Na]⁺.
(7 R ,8 R )-7-(Acetyloxy)-11-oxo-1,5-dithiaspiro[5.5]undec-8-yl Acetate (17): white solid; mp 82-84 ˚C; [α]_D +163.1
(c = 1, CHCl₃). IR (neat): 2924, 2854, 1747, 1236, 721 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 1.95-2.07 (m, 6 H), 2.11 (s, 3 H), 2.13-2.31 (m, 1 H), 2.41-2.55 (m, 1 H), 2.66-2.84 (m, 2 H), 2.91-3.24 (m, 3 H), 5.72-5.83 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 200.9, 170.0, 169.5, 73.9, 67.5, 59.6, 33.8, 26.9, 26.4, 24.6, 24.0, 20.7, 20.4. MS (ESI): m/z = 319 [M + H]⁺.
(10 R,11 R )-10,11-Dihydroxy-1,5-dithiaspiro[5.5]undecan-7-one (18): white solid; mp 101-103 ˚C; [α]_D +145.9 (c = 1, CHCl₃). IR (neat): 3446, 2924, 1705, 1219, 771 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.25 (s, 1 H), 1.52-1.69 (m, 1 H), 1.76-1.93 (m, 1 H), 2.03-2.26 (m, 2 H), 2.34-2.44 (m, 1 H), 2.60-2.70 (m, 3 H), 2.87-3.03 (m, 1 H), 3.18-3.32 (m, 1 H), 3.52 (d, J = 9.0 Hz, 1 H), 3.70-3.81 (m, 1 H), 4.08-4.18 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 202.7, 78.9, 68.4, 67.0, 33.3, 27.3, 26.9, 26.1, 24.2. MS (ESI): m/z = 257 [M + Na]⁺.
(10 R,11 R )-10-[1-( tert -Butyl)-1,1-dimethylsilyl]oxy-11-hydroxy-1,5-dithiaspiro[5.5]undecan-7-one (19): semi solid; [α]_D +93 (c = 1.25, CHCl₃). IR (neat): 3504, 2928, 2855, 1709, 1109, 837 cm^-¹. ^¹H NMR (300 MHz, CDCl₃):
δ = 0.12 (s, 3 H), 0.15 (s, 3 H), 0.92 (s, 9 H), 1.42 (s, 1 H), 1.74-1.93 (m, 2 H), 2.01-2.21 (m, 2 H), 2.54-2.68 (m, 3 H), 2.87-3.00 (m, 2 H), 3.26-3.38 (m, 1 H), 3.97 (d, J = 2.2 Hz, 1 H), 4.35-4.42 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 207.2, 78.2, 77.7, 75.6, 30.8, 29.4, 27.0, 26.1, 25.5, 20.4, 17.9, -5.12, -5.17. MS (ESI): m/z = 371 [M + Na]⁺.
tert -Butyl[(3 S ,10 R ,11 R )-10-methoxy-1-oxa-5,9-dithiadispiro[2.0.5.4]tridec-11-yl]oxydimethylsilane (21): yellow oil; [α]_D -21.9 (c = 0.35, CHCl₃). IR (neat): 3373, 2922, 2853, 2365, 1466, 756 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 0.09 (s, 3 H), 0.10 (s, 3 H), 0.90 (s, 9 H), 1.53-2.19 (m, 5 H), 2.37-2.74 (m, 4 H), 3.21-3.40 (m, 2 H), 3.42-3.54 (m, 2 H), 3.56 (s, 3 H), 4.17-4.29 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 88.6, 83.0, 71.3, 69.8, 52.7, 32.0, 31.1, 30.6, 29.6, 29.3, 28.1, 27.4, 25.8, 24.5, -4.7.
MS (ESI): m/z = 399 [M + Na]⁺.
(3 S ,5 R ,6 R )-6-[1-( tert -Butyl)-1,1-dimethylsilyl]oxy-5-methoxy-1-oxaspiro [2.5]octan-4-one (3): yellow oil; [α]_D -1.20 (c = 1, CH₂Cl₂). IR (neat): 2922, 2852, 1737, 1461, 762 cm^-¹. ^¹H NMR (200 MHz, CDCl₃) : δ = 0.07 (s, 3 H), 0.08 (s, 3 H), 0.92 (s, 9 H), 1.40-1.60 (m, 1 H), 2.00-2.20 (m, 2 H), 2.40-2.60 (m, 1 H), 2.77 (d, J = 4.7 Hz, 1 H), 3.29 (d, J = 4.7 Hz, 1 H), 3.44 (s, 3 H), 3.98 (d, J = 2.5 Hz, 1 H), 4.44 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 202.4, 87.5, 72.3, 60.7, 58.5, 51.4, 28.9, 27.1, 25.9, 18.3, -4.4, -5.0. MS (ESI): m/z = 309 [M + Na]⁺.
(-)-Ovalicin (1): white solid; mp 94-95 ˚C; [α]_D -112 (c = 0.2, CHCl₃). IR (neat): 3438, 2923, 2853, 1728, 1627, 1459, 1216, 761 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 1.37 (s, 3 H), 1.41-1.45 (m, 1 H), 1.66 (s, 3 H), 1.75 (s, 3 H), 2.12-2.18 (m, 1 H), 2.30-2.45 (m, 2 H), 2.61-2.71 (m, 2 H), 2.73 (d, J = 4.2 Hz, 1 H), 2.90 (t, J = 6.3 Hz, 1 H), 3.10 (d, J = 4.2 Hz, 1 H), 3.14 (s, 1 H), 3.57 (s, 3 H), 4.23 (s, 1 H), 5.18 (t, J = 6.6 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 206.8, 135.7, 118.2, 86.3, 78.8, 60.7, 60.5, 59.5, 57.0, 51.5, 36.9, 30.5, 27.2, 25.9, 18.2, 14.6. MS (ESI): m/z = 319 [M + Na]⁺.