Beruflich Dokumente
Kultur Dokumente
alkaloids include elaeocarpine (&), isoelaeocarpine(2_),and isoelaeocarpicine(a), representative of the aromatic Elaeocarpus alkaloids. The leaf alkaloids derived from Elaeocarpus
kaniensis Schltr., a large tree found in the rain-forests of New Guinea, contains none of the
more connnonindolizidinealkaloids (e.g., 1, 2, or 2).
4445
30. 46
4446
Scheme
l-i
+
I>
-O/N+
MC
labile, B-aminoketone2 was obtained by Jones oxidation. This ketone, bp 53-54C (0.07 mm),
was used directly without purification. When this crude 6-aminoketonewas treated with
acrolein (1 equiv.) in benzene containing potassium t-butylate (3 equiv.), a chromatographitally separable mixture (45%) of dl-elaeokanine-A(9) and an unsatured aldehyde (i.e., 11)
are formed in a 4:l ratio, respectively. The dl-elaeokanine-A (picrate mp 134-136C) exhibits
strong carbonyl absorption at 1670 cm-' (IR;
CDC13) 6 0.92 (t, 3, J = 7 Hz), 1.1-2.0 (m, 5), 2.04-3.18 (m, 9), 3.44 (broad t, 1), and 6.82
lc
ppm (m, 1)) identical to those of d-elaeokanine-A.
Aldehyde 11, picrate mp 169-171'C dec., the alternate (i.e. to 3) aldol product derived
xn. Lh
4447
EtOH) at 246 nm (e 11,930). Its NMR spectrum (100 MHz, CDC13) reveals the presence of the
F;
aldehydo proton at 6 10.12 ppm (s, 1) and the C-5 equatorial proton" as a sharp doublet at 6
3.84 ppm (J = 16 Hz).
When the crude @aminoketone 2, derived from the Jones oxidation of B is exposed to
acrolein (1 equiv.) in methylene chloride, followed (after solvent removal) by concentrated
hydrochloric acid (2h, 25(Z),there results a chromatographicallyseparable mixture (44% from
2) of dl-elaeokanine-Cand aldehyde 11, in a 3:1 ratio respectively. The elaeokanine-C.mp
69-70C, exhibits IR (CC14; 3470 and 1710 cm-') and NMR (100 MHz, CDC13) behavior (6 0.88 (t,
3, J = 7.0 Hz), 1.0-3.2 (m, 16), 3.56 (broad s, 1, cont. dependent), and 4.16 ppm (q, 1, J =
2.2 Hz)) identical to that reported for the natural product.lc The magnitude of the coupling
constants observed for the equatorial H-7 proton supports the assigned configurationlc (cf.
w.
Interestingly,we could not detect the C-7 epimer of 2 from the acid catalyzed aldol
cyclization.
We believe that elaeokanine-C (3) is the product of kinetic, rather than thermodynamic
control, since exposure of the synthetic alkaloid to concentrated hydrochloricacid for 2 h
at 25'C leaves it unaltered. An NMR examination of the product derived from this acid
treatment shows the absence of both aldehyde ii, a product which would be anticipated if the
aldol process were reversible, and elaeokanine-A. Indeed, the NMR spectrum so obtained is
virtually identical to that of the starting material.
H30+
a
I0 -
o&-Pr
5a
at the transition state for the IQ + 2 process is facilitated by hydrogen bonding involving
the enolic hydroxyl function (cf., 10e) and the aldehyde carbonyl. The aldol closure of
19~ directly affords 2 with the correct relative stereochemistryat C-7, C-8, and C-9 (cf.
Z!). Indeed, such a stereospecificprocess may be involved in the biogenesis of these
alkaloids since the C-7 epimers of the Elaeocarpus alkaloids have not been reported.
AA48
Acknowledgement - We wish to thank the Institute of General Medical Sciences of the NIH for
financial assistance (GM 25303). Moreover, we are grateful to Dr. J. A. Lamberton (CSIRO,
Melbourne) for the NMR and IR spectra of natural d-elaeokanine-Aand dl-elaeokanine-C,and
for IR (KBr) spectra of the methiodide of both natural and synthetic elaeokanine-C.
References and Notes
1.
2.
3.
For previous synthetic efforts regarding these alkaloids, see ref. lc.
4.
5.
6.