Otteliones A and B isolated from the freshwater plant Ottelia alismoides have attracted significant attention because of their potential as novel anticancer agents. In this review four independent enantioselective total syntheses and one formal synthesis of these natural products are presented with particular focus on their methodology and strategy.
AyyadaS-EN, JuddAS, ShierWT, HoyeTR. (1998) Otteliones A and B: Potently cytotoxic 4-methylene-2-cyclohexenones from Ottelia alismoides. Journal of Organic Chemistry, 63, 8102–8106.
2.
BeckersT, MahboobisS., (2003) Natural, semisynthetic and synthetic microtubule inhibitors for cancer therapy. Drugs of the Future, 28, 767–785.
3.
PerezEA. (2009) Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Molecular Cancer Therapeutics, 8, 2086–2095.
4.
CombeauC, ProvostJ, LancelinF, TournouxY, Prod′hommeF, HermanF, LavelleF, LeboulJ, VuilhorgneM. (2000) RPR112378 and RPR115781: Two representatives of a new family of microtubule assembly inhibitors. Molecular Pharmacology, 57, 553–563.
5.
MehtaG, ReddyDS. (1999) Synthetic studies directed towards the potent cytotoxic natural product ottelione A: Stereoselective construction of the complete framework. Chemical Communications, 2193–2194.
6.
TrembleauL, PatinyL, GohsezL., (2000) Diels–Alder reaction of activated furans to cyclopentenone derivatives: A regiodivergent Diels–Alder approach towards polyfunctionalized cis-hydrindanones, Tetrahedron Letters, 41, 6377–6381.
7.
MehtaG, IslamK., (2000) An eventful synthetic approach towards the biologically potent natural product ottelione A: Enantio-, regio- and stereoselective construction of the bicyclic core. Synlett, 1473–1475.
8.
MehtaG, IslamK., (2002) Total synthesis of epi-otteliones. Organic Letters, 4, 2881–2884.
9.
CliveDLJ, FletcherSP. (2002) Synthesis of the bicyclic dienone core of the antitumor agent ottelione B. Chemical Communications, 1940–1941.
10.
ArakiH, InoueM, KatohT., (2003) Enantioselective total synthesis of 3-epi-ottelione A. Synlett, 2401–2403.
11.
CliveDLJ, LiuD., (2005) A short synthetic route to the core structure of otteliones A and B. Tetrahedron Letters, 46, 5305–5307.
12.
BetkekarVV, PandS, KaliappanKP. (2012) A tandem enyne/ring closing metathesis approach to 4-methylene-2-cyclohexenols: An efficient entry to otteliones and loloanolides. Organic Letters, 14, 198–201.
13.
LestiniE, RobertsonK, MurphyCD, ParadisiF., (2012) Alternative mild route to the synthesis of 4-methylenecyclohex-2-enone, a key moiety of the anticancer compounds otteliones A and B. Synthetic Communications, 42, 1864–1876.
14.
MehtaG, IslamK., (2002) Total synthesis of (±)-otteliones A and B. Angewandte Chemie, International Edition, 41, 2396–2398.
15.
MehtaG, IslamK., (2003) Enantioselective total synthesis of (+)- and (-)-ottelione A and (+)- and (-)-ottelione B. Absolute configuration of the novel, biologically active natural products. Tetrahedron Letters, 44, 6733–6736.
16.
ArakiH, InoueM, KatohT., (2003) Total synthesis and absolute configuration of otteliones A and B, novel and potent antitumor agents from a freshwater plant. Organic Letters, 5, 3903–3906.
17.
ArakiH, InoueM, SuzukiT, YamoriT, KohnoM, WatanabeK, AbeH, KatohT., (2007) Enantioselective total synthesis of (+)-ottelione A, (-)-ottelione B, (+)-3-epi-ottelione A and preliminary evaluation of their antitumor activity. Chemistry-A European Journal, 13, 9866–9811.
18.
CliveDLJ, LiuD., (2007) Synthesis of the otteliones A and B: Use of a cyclopropyl group as a vinyl equivalent. Angewandte Chemie, International Eddition, 46, 3738–3740.
19.
CliveDLJ, LiuD., (2007) Synthesis of the potent anticancer agents ottelione A and ottelione B in both racemic and natural optically pure forms. Journal of Organic Chemistry, 73, 3078–3087.
20.
ChenC-H, ChenY-K, ShaC-K. (2010) Enantioselective total synthesis of otteliones A and B. Organic Letters, 12, 1377–1379.
21.
LeeMY, KimKH, JiangS, JungYH, SimJY, HwangG-S, RyuDH. (2008) Enantioselective formal synthesis of antitumor agent (+)-ottelione A. Tetrahedron Letters, 49, 1965–1967.
22.
IzuharaT, KatohT., (2000) Enantiocontrolled synthesis of (4S,5S,6S)-6-benzyl-4,5-epoxy-6-hydroxy-2-cyclohexen-1-one, a model compound for the epoxycyclohexenone moiety of scyphostatin. Tetrahedron Letters, 41, 7651–7655.
23.
IzuharaT, KatohT., (2001) Studies toward the total synthesis of scyphostatin: First entry to the highly functionalized cyclohexenone segment. Organic Letters, 3, 1653–1656.
24.
KatohT, IzuharaT, YokotaY, InoueM, WatanabeK, NobeyamaA, SuzukiT., (2006) Enantiocontrolled synthesis of the epoxycyclohexenone moieties of scyphostatin, a potent and specific inhibitor of neutral sphingomyelinase. Tetrahedron, 62, 1590–1608.
SuzukiT, GhozatiK, ZhouD-Y, KatohT, SasaiH. (2010) Formal total synthesis of ottelione using iridium-catalyzed oxidative desymmetrization. Tetrahedron, 66, 7562–7568.
27.
CoreyEJ, WinterRAE. (1963) New stereospecific olefin synthesis from 1,2-diols. Journal of the American Chemical Society, 85, 2677–2678.
28.
CoreyEJ, CareyFA, WinterRAE. (1965) Stereospecific syntheses of olefins from 1,2-thiocarbonates and 1,2-trithiocarbonates. trans-Cycloheptene. Journal of the American Chemical Society, 87, 934–935.
KonnoH, OgasawaraK., (1999) A practical preparation of versatile cyclohexenoid chiral building blocks. Synthesis, 1135–1140.
31.
LombardoL. (1982) Methylenation of carbonyl compounds with zinc-dibromomethane-titanium tetrachloride. Application to gibberellins. Tetrahedron Letters, 23, 4293–4296.
32.
BarrettAGM, LeboldSA. (1990) (Phenylthio)nitromethane in the total synthesis of polyoxin C. Journal of Organic Chemistry, 55, 3853–3857.
33.
CominsDL, DehghaniA., (1992) Pyridine-derived triflating reagents: An improved preparation of vinyl triflates from metallo enolates. Tetrahedron Letters, 33, 6299–6302.
34.
SchwabP, FranceMB, ZillerJW, GrubbsRH. (1995) A series of well-defined metathesis catalysts-synthesis of [RuCl2(:CHR′)(PR3)2] and their reactions. Angewandte Chemie, International Edition in English, 34, 2039–2041.
35.
MiyauraN, IshiyamaT, SasakiH, IshikawaM, SatoM, SuzukiA., (1989) Palladium-catalyzed inter- and intramolecular cross-coupling reactions of B-alkyl-9-borabicyclo[3.3.1]nonane derivatives with 1-halo-1-alkenes or haloarenes. Synthesis of functionalized alkenes, arenes, and cycloalkenes via a hydroboration-coupling sequence. Journal of the American Chemical Society, 111, 314–321.
36.
AudiaJE, BoisvertL, PattenAD, VillalobosA, DanishefskySJ. (1989) Synthesis of two useful, enantiomerically pure derivatives of (S)-4-hydroxy-2-cyclohexenone. Journal of Organic Chemistry, 54, 3738–3740.
37.
ItoY, HiraoT, SaegusaT., (1978) Synthesis of α,β-unsaturated carbonyl compounds by palladium(II)-catalyzed dehydrosilylation of silyl enol ethers. Journal of Organic Chemistry, 43, 1011–1013.
38.
CampsP, GanzálezA, Muñoz-TorreoD, SimonM, ZúñigaA, MartinsMA, Font-BardiaM, SolansX. (2000) Synthesis of polysubstituted bicycle[3.3.1]nonane-3,7-diones from cyclohexa-2,5-dienones and dimethyl 1,3-acetonedicarboxylate. Tetrahedron, 56, 8141–8151.
39.
PirrungMC, NunnDS. (1992) Synthesis of quinone monoketals by diol exchange. Tetrahedron Letters, 33, 6591–6594.
40.
RyuDH, KimKH, SimJY, CoreyEJ. (2007) Catalytic enantioselective Diels–Alder reactions of furans and 2,2,2-trifluoroethyl acrylate. Tetrahedron Letters, 48, 5735–5737.
41.
ChangT-Y, TuY-P, WeiW-Y, ChenHY, ChenC-S, LeeY-SE, HuangJ-J, ShaC-K. (2012) Synthesis and antiproliferative activities of ottelione A analogues. Medicinal Chemistry Letters, 3, 1075–1080.