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Synthesis of ( )−neolaxiflorin L (2). To a stirred solution of ( )−3 (1.0 g, 2.47
mmol) in acetone (250 mL) was added Jones reagent (1.7 mL of a 2.9 M in acetone/
water solution, 4.9 mmol) at 0 °C. After stirring at 0 °C for 15 min, the reaction was
quenched by addition of a saturated NaHCO3 aqueous solution (2.5 mL) and iso-
propanol (3.5 mL). After dilution with hexanes (500 mL), the solution was filtered
through a plug of silica gel and then concentrated. Silica gel flash column chro-
matography (hexanes/ethyl acetate = 5:1) of the residue gave a white solid (0.82 g,
2.28 mmol, 92%) as the product.
17. Church, R. F., Ireland, R. E. & Marshall, J. A. Experiments directed toward the
total synthesis of terpenes. VII. The synthesis of ( )-8β-carbomethoxy-13-
oxopodocarpanone, a degradation product of phyllocladene. J. Org. Chem. 31,
2526–2530 (1966).
18. Bell, R. A., Ireland, R. E. & Partyka, R. A. Experiments directed toward the
total synthesis of terpenes. VIII. The total tynthesis of ( )-Kaurene and
( )-Atisirene. J. Org. Chem. 31, 2530–2536 (1966).
19. Mori, K. & Matsui, M. Total synthesis of ( )-kaur-16-en-19-oic acid.
Tetrahedron Lett. 7, 175–180 (1966).
Synthesis of ( )-eriocalyxin B (1). To a stirred mixture of ( )−2 (0.27 g, 0.78
mmol), NaI (1.05 g, 7.02 mmol) and HMDS (2.45 mL, 11.7 mmol) in CH3CN (4
mL) was added TMSCl (0.53 mL, 3.9 mmol) slowly at 0 °C. After stirring at room
temperature for 12 h, the reaction was diluted with hexanes (30 mL), and quenched
by addition of water (5 mL). The aqueous phase was extracted with hexanes (20
mL × 3). The combined organic extracts were washed with water until clear, and
then washed with brine, dried over MgSO4, filtered and concentrated. To a stirred
solution of the residue in CH3CN (8 mL) was added Pd(OAc)2 (525 mg, 2.34
mmol) at room temperature. After stirring at room temperature for 6 h, the
reaction was quenched by addition of a 0.5 N HCl aqueous solution (7 mL). The
aqueous phase was extracted with ethyl acetate (20 mL × 3). The combined organic
extracts were washed with brine, dried over MgSO4, filtered and concentrated.
Silica gel flash column chromatography (hexanes/ethyl acetate = 2:1) of the residue
gave a white solid (0.21 g, 0.62 mmol, 79%) as the product.
20. Mori, K., Nakahara, Y. & Matsui, M. Total synthesis of ( )-steviol.
Tetrahedron Lett. 11, 2411–2414 (1970).
21. Ziegler, F. E. & Kloek, J. A. 1-Hydroxy-7-methylene bicyclo [3.2. 1] octane: a
gibbane-steviol C/D ring model. Tetrahedron Lett. 12, 2201–2203 (1971).
22. Nakahara, Y., Mori, K. & Matsui, M. Diterpenoid total synthesis: Part XVI.
Alternative synthetic routes to ( )-steviol and ( )-kaur-16-en-19-oic acid.
Agric. Biol. Chem. 35, 918–928 (1971).
23. Mori, K., Nakahara, Y. & Matsui, M. Diterpenoid total synthesis—XIX:
( )-steviol and erythroxydiol A: rearrangements in bicyclooctane compounds.
Tetrahedron 28, 3217–3226 (1972).
24. Ziegler, F. E. & Kloek, J. A. The stereocontrolled photoaddition of allene to
cyclopent-1-ene-1-carboxaldehydes. A total synthesis of ( ) steviol methyl
ester and isosteviol methyl ester. Tetrahedron 33, 373–380 (1977).
25. Corey, E. J., Wess, G., Xiang, Y. B. & Singh, A. K. Stereospecific total synthesis
of ( )-cafestol. J. Am. Chem. Soc. 109, 4717–4718 (1987).
26. Singh, A. K., Bakshi, R. K. & Corey, E. J. Total synthesis of ( )-atractyligenin.
J. Am. Chem. Soc. 109, 6187–6189 (1987).
27. Paquette, L. A. & Ladouceur, G. Synthetic studies targeted at the cytotoxic 8,
9-seco-ent-kaurene diterpenes. Concise complementary stereocontrolled
construction of the bridgehead olefin core. J. Org. Chem. 54, 4278–4279
(1989).
28. Paquette, L. A., Backhaus, D. & Braun, R. Direct asymmetric entry into the
cytotoxic 8, 9-Secokaurene diterpenoids. Total synthesis of (−)-O-
methylshikoccin and (+)-O-(methylepoxy) shikoccin. J. Am. Chem. Soc. 118,
11990–11991 (1996).
29. Backhaus, D. & Paquette, L. A. Synthetic entry into the ent-kaurene
framework. Application of an unprecedented transannular cyclization for
forming the central bond common to the B and C rings. Tetrahedron Lett. 38,
29–32 (1997).
Data availability. The X-ray crystallographic coordinates for structures reported in
this article have been deposited at the Cambridge Crystallographic Data Centre
(CCDC), under deposition number CCDC 1556435 for ( )-neolaxiflorin L (2),
CCDC 1556434 for ( )−12, CCDC 1556436 for ( )−16 and CCDC 1556433 for
( )-15-epi-enmelol (17). These data can be obtained free of charge from The
data supporting the findings of this study are available within the paper and its
supplementary information files and also are available from the corresponding
author upon request.
Received: 26 October 2017 Accepted: 20 February 2018
30. Corey, E. J. & Liu, K. Enantioselective total synthesis of the potent anti-HIV
agent neotripterifordin. Reassignment of stereochemistry at C (16). J. Am.
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31. Cherney, E. C., Green, J. C. & Baran, P. S. Synthesis of ent-kaurane and
beyerane diterpenoids by controlled fragmentations of overbred intermediates.
Angew. Chem. Int. Ed. 52, 9019–9022 (2013).
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