DOI: 10.1002/chem.201406434
Communication
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Total Synthesis |Hot Paper|
Enantiospecific Total Syntheses and Assignment of Absolute
Configuration of Cannabinol-Skeletal Carbazole Alkaloids
Murrayamines-O and -P
Dattatraya H. Dethe,* Saikat Das, Balu D. Dherange, and Samarpita Mahapatra[a]
Dedicated to Dr. A. V. Rama Rao on the occasion of his 80th birthday
natural products either by chiral pool or asymmetric catalytic
Abstract: First enantiospecific total syntheses of the can-
synthesis.[9] With our ongoing interest in total synthesis[10–12] of
nabinol-skeletal carbazole alkaloids murrayamines-O and
biologically active natural products,[13,14] herein we report the
-P isolated from root barks of Murraya euchrestifoli, have
first enantiospecific total syntheses of murrayamine-O (1) and
been accomplished by highly diastereoselective, Lewis
murrayamine-P (2) as well as their antipodes ent-1 and ent-2,
acid catalyzed coupling reactions of commercially avail-
respectively, facilitated by Lewis acid catalyzed coupling of
able monoterpenes with carbazole derivative, which in ad-
cyclic allylic alcohol 6 with carbazole derivative 7 for one pot
dition to confirming the structure also established the ab-
CÀC and CÀO bond formation and a strategic effort to avoid
solute configuration of the natural products. Synthesis of
the use of protecting group and expensive reagents.
both natural products and their enantiomers was achieved
It was envisioned that murrayamine-O/P could be obtained
with high atom economy, in a protecting-group free
from compound 8 by regioselective epoxide ring opening. Ep-
manner and in six steps longest linear sequence from
oxide 8 could be easily accessed from compound 9 by diaste-
commercially available aniline derivative and verbenol.
reoselective epoxidation. The key intermediate 9 in turn could
be obtained by treatment of carbazole derivative 7 with verbe-
Murrayamines-O (1) and -P (2) are the two novel pentacyclic al-
kaloids isolated from the plant of genus Murraya.[1] Both 1 and
2 are the first representatives of cannabinol-skeletal carbazole
alkaloids. Murraya is a genus of flowering plants in the citrus
family Rutaceae, that has been used in traditional medicine for
the treatment of fever, pain, diabetics, dysentery, painful in-
flammatory conditions, to induce labor and for cancer treat-
ments.[2] Murrayamine and related carbazole alkaloids have
been reported to show a potent antiplatelet aggregation activ-
ity.[3] The structure of 1 and 2 were determined by extensive
1D and 2D NMR analysis. The relative stereochemistry was as-
signed based on splitting patterns; coupling constants and
NOESY experiments revealed a trans fused chair-like oxadecalin
Scheme 1. Retrosynthetic analysis of murrayamine-O (1).
core and the equatorial C-3 methyl.
So far more than fifty natural products belonging to this
family and having various potent biological activities have
been isolated.[4] Although there have been no synthesis report-
ed of murrayamine-O/P, recently racemic total synthesis of
some natural products of this class such as murrayazoline
(3),[5,6] cyclomahanimbine (4),[6] murrafoline-A (5),[7] and related
natural products[8] have been reported in the literature. Also,
there are few reports on enantioselective synthesis of these
[a] Dr. D. H. Dethe, S. Das,+ B. D. Dherange,+ S. Mahapatra
Department of Chemistry
Indian Institute of Technology Kanpur, Kanpur 208016 (India)
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201406434.
Scheme 2. Synthesis of carbazole derivative 7.
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2015, 21, 1 – 5
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