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Although the biosynthesis of β-amyrin is known to proceed via 2,3-oxidosqualene, the
fact that β-amyrin has been obtained after enzymatic cyclization of the 2,3-epoxide
of racemic 1 should be also taken into account. Furthermore, oxidosqualene cyclase mutagenesis
experiments, included those in which achilleol A and camelliol C are biosynthesized
by mutant OSC, suggested that relatively few changes in the enzyme are needed to alter
product specificity. These findings ultimately supported the existence of alternative
pathways in the biosynthesis of terpenoids. For OCS mutagenesis experiments, see:
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<A NAME="RG02805ST-3C">3c</A> For biosynthesis of β-amyrin from the 2,3-epoxide of racemic 1, see:
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<A NAME="RG02805ST-5">5</A> To our knowledge, only Theodorakis et al. have assayed the enantioselective variant
of this reaction in their synthesis of (-)-acanthoic acid. Although the condensation
reaction was attempted in the presence of different optically active catalysts, the
highest ee obtained were of 60%:
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<A NAME="RG02805ST-8">8</A> Reports by Barton and van Tamelen, showing that the use of different epimers
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to pursue the enantioselective synthesis of these irregular triterpenes:
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<A NAME="RG02805ST-11">11</A>
Procedure for the Enantioselective Variant of the Robinson Annulation Using the Nazarov
Reagent and a Chiral Enamine: Synthesis of Bicyclic 12.
A stirred solution of enamine 9 (486 mg, 2 mmol) and Nazarov reagent 10 (256 mg, 2 mmol) in dry benzene (2 mL) was
heated at 65-70 °C for 1 h. Then was added 0.5 mL of a solution of 125 g of NaOAc,
25 mL of H2O and 25 mL of HOAc. The mixture was heated for 1 h, washed with H2O, sat. aq NaHCO3, and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The resulting crude product was purified
by column chromatography (hexane-t-BuOMe, 4:1) to afford 150 mg of 11 (20%) and 106 mg of 12 (21%). Keto ester 12 was isolated as colorless oil. [α]D -49.7 (c 0.7, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 3.79 (s, 3 H), 2.52 (ddd, J = 5.4, 14.3, 17.0 Hz, 1 H), 2.40 (dt, J = 3.9, 17.0 Hz, 1 H), 2.15 (d, J = 14.6 Hz, 1 H), 1.98 (dd, J = 1.3, 14.6 Hz, 1 H), 1.86 (td, J = 4.6, 13.7 Hz, 1 H), 1.78 (dq, J = 3.2, 13.6 Hz, 1 H), 1.47-1.67 (m, 3 H), 1.28-1.37 (m, 1 H), 1.23 (s, 3 H), 1.00 (s,
3 H), 0.82 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 195.0, 167.7, 166.4, 132.3, 52.0, 43.0, 37.8, 37.1, 34.4, 34.0, 33.5, 32.4,
32.0, 24.6, 22.3. IR (film): 2945, 2866, 1735, 1671, 1617, 1465, 1353, 1227, 1131,
1008 cm-1. HRMS-FAB: m/z calcd for C15H22O3Na [M + Na]+: 273.1467; found: 273.1463.
<A NAME="RG02805ST-12">12</A>
The enantioselectivity of the annelation reaction could be measured after treating
15 with (S)-2-acetoxypropionyl chloride. The diastereomeric ratio of the corresponding lactates
was determined by 1H NMR (800 MHz) spectroscopy, by integrating the AB quartets of the major and minor
components.
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Gibson CP.
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<A NAME="RG02805ST-14">14</A>
All new compounds gave satisfactory analytical and spectroscopic data.
Compound 14: colorless oil. [α]D +30.8 (c 0.5, CHCl3). 1H NMR (400 MHz, C6D6): δ = 3.51 (s, 3 H), 2.68 (dd, J = 2.9, 12.4 Hz, 1 H), 2.03 (s, 3 H), 1.97-2.07 (m, 2 H), 1.84 (ddd, J = 6.8, 11.8, 24.5 Hz, 1 H), 1.57-1.65 (m, 2 H), 1.35 (dt, J = 3.9, 13.6 Hz, 1 H), 1.25 (td, J = 3.4, 13.6 Hz, 1 H), 1.15 (br d, J = 13.6 Hz, 1 H), 1.08 (t, J = 13.0 Hz, 1 H), 1.02 (s, 3 H), 0.93 (s, 3 H), 0.93 (s, 3 H), 0.73 (dd, J = 6.9, 14.7 Hz, 1 H). 13C NMR (100 MHz, C6D6): δ = 169.0, 142.8, 129.3, 50.7, 43.8, 40.0, 36.5, 34.8, 33.1, 31.4, 31.1, 31.0,
27.0, 26.3, 24.1, 21.9. IR (film): 2949, 2922, 2851, 1713, 1640, 1464, 1258, 1063,
804 cm-1. HRMS-FAB: m/z calcd for C16H26O2Na [M + Na]+: 273.1831; found: 273.1830.
<A NAME="RG02805ST-15A">15a</A> (+)-α- and (+)-γ-polypodatetraenes have been isolated form the leaves of Polypodium and Polystichum species:
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Arai Y.
Masuda K.
Kamada T.
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<A NAME="RG02805ST-15B">15b</A> Although recently both polypodatetraenes have been reported from (-)-albi-canol
and (-)-drimenol by Akita et al., the method used by these authors supposed an elongation
of the carbon chain of the sesquiterpenic precursors, as a previous step to the key
C-20+C-10 coupling process:
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