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DOI: 10.1055/s-0030-1259943
Biomimetic Synthesis of (+)-Neroplofurol
Publication History
Publication Date:
07 April 2011 (online)
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Abstract
(+)-Neroplofurol was biomimetically synthesized in only two steps from natural (+)-nerolidol via Sharpless dihydroxylation and a cascade Shi epoxidation/epoxide ring-opening reaction. All carbons are derived from natural (+)-nerolidol and no protecting groups were utilized, making the synthesis atom-economical and highly efficient. The synthetic neroplofurol was proved to be the enantiomer of the natural one, according to ¹H NMR, ¹³C NMR spectra and optical rotation value. The absolute configuration of natural neroplofurol was also deduced to be 3R,6S,7R,10S.
Key words
Sharpless dihydroxylation - Shi epoxidation - cascade reaction - atom economic - biomimetic synthesis
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References and Notes
(-)-Nerolidol was purchased from Sanming Meilie Perfumery Factory, Fuzhou City, Fujian Province; [α]D 25 +12.
11Spectral data of the target compound:
(+)-neroplofurol (1): [α]²5
D +20
(c = 0.1, MeOH). ¹H
NMR (400 MHz, CDCl3):
δ = 1.11
(s, 3 H), 1.13 (s, 3 H), 1.25 (s, 3 H), 1.27 (s, 3 H), 1.35 (m,
1 H), 1.48 (m, 1 H), 1.53 (dddd, J = 14.0,
7.2, 7.2, 2.0 Hz, 1 H), 1.66 (ddd, J = 14.4,
7.2, 7.2 Hz, 1 H), 1.78 (ddd, J = 14,2,
7.0, 6.9 Hz, 1 H), 1.90 (m, 2 H), 2.10 (ddd, J = 2.4, 6.0,
12.5 Hz, 1 H), 3.54 (dd, J = 10.8,
2.0 Hz, 1 H), 3.79 (dd, J = 7.6,
7.2 Hz, 1 H), 5.04 (dd, J = 10.8,
1.2 Hz, 1 H), 5.21 (dd, J = 17.6,
1.6 Hz, 1 H), 5.84 (dd, J = 17.6,
10.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 23.86,
25.56, 26.37, 26.95, 27.61, 28.85, 31.32, 39.34, 72.08, 72.91, 77.86,
84.41, 86.46, 112.04, 145.02. IR (solid): 3375, 2971, 1374, 1082 cm-¹.
HRMS (ESI): m/z [M + Na]+ calcd
for C15H28O4Na: 295.1885; found:
295.1884.
Representative
Experimental Procedure: A solution of AD-mix-β (1.4
g), in t-BuOH-H2O
(5:5, 10 mL) was cooled at 0 ˚C. Stirring the mixture at
r.t. produced two clear phases; then the methanesulfonamide (95
mg) was added. After stirring for 5 min at 0 ˚C, the olefin 3 (232 mg, 1 mmol) was added in one portion.
The reaction mixture was stirred at 0 ˚C for 24 h and then
quenched with solid sodium sulfite (1.5 g). The stirring was continued
for 45 min, and the solution was extracted with EtOAc (3 × 20
mL). The combined organic phases were washed (2 N KOH), treated
with brine, dried (MgSO4), and concentrated. After a
short silica gel chromatography, the crude product was then dissolved
in MeCN-dimethoxymethane mixture (30 mL, 1:2). A buffer solution
(0.5 M solution of Na2B4O7˙10H2O
in 4 × 10-4 aq Na2EDTA,
20 mL), Bu4NHSO4 (20 mg) and Shi’s
catalyst 6 (180 mg) were added subsequently
to the solution. The mixture was cooled to 0 ˚C. A solution
of Oxone (560 mg) in aq Na2
(EDTA) (4 × 10-4 M,
13 mL) and K2CO3 (13 mmol) in H2O
(13 mL) were added separately over a period of 1 h (using syringe
pumps) dropwise to the mixture. After the additions were done, the
mixture was stirred for an addi-
tional 30 min at 0 ˚C,
diluted with H2O, and extracted with EtOAc (3 × 60
mL). The combined organic layer was washed with brine, and dried
over Na2SO4. The product was purified by flash
chromatography on silica gel; yield: 176 mg, 0.6 mmol, 60%.