Tetrahedron Letters
Model studies on construction of the oxabicyclic [3.3.1] core
of the mulberry Diels–Alder adducts morusalbanol A
and 441772-64-1
b
a
a
Jia Ti Tee a, Chin Fei Chee a,b, , Michael J. C. Buckle , Vannajan Sanghiran Lee , Wei Lim Chong ,
⇑
Hamid Khaledi c, Noorsaadah Abd Rahman a
a Drug Design and Development Research Group, Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
b Department of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia
c Center for Natural Products and Drug Research, University of Malaya, 50603 Kuala Lumpur, Malaysia
a r t i c l e i n f o
a b s t r a c t
Article history:
Preparation of the oxabicyclic [3.3.1] cores of morusalbanol A and 441772-64-1 was achieved via the
intramolecular cyclization of cis–trans (endo) mulberry Diels–Alder adducts. The latter were derived from
a hydrogen bond-assisted regioselective Diels–Alder reaction between a chalcone dienophile and a dehy-
droprenyl diene. Results from these studies provide important insights into the syntheses of morusal-
banol A and related mulberry Diels–Alder adducts.
Received 29 May 2015
Revised 9 July 2015
Accepted 15 July 2015
Available online 20 July 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Morusalbanol A
Diels–Alder
Morus alba
Mulberry
Oxabicyclic
Introduction
of cis-trans (endo) and trans–trans (exo) Diels–Alder adducts in one
step. Adducts having the cis–trans stereochemistry on the cyclo-
Morusalbanol A is a mulberry Diels–Alder adduct isolated from
the bark of Morus alba, which exhibits interesting neuroprotective
activity.1 The structure of morusalbanol A is characterized by an
oxabicyclic [3.3.1] core which is derived from the intramolecular
cyclization of a cis–trans (endo) mulberry Diels–Alder adduct.
Morusalbanol A shows evidence of atropisomerism due to the rota-
tional hindrance of the D/E-rings about the C5-C15 and C4-C8-C9
bonds (Fig. 1).1 Additional examples of other natural products in
this class are cathayanon E,2 wittiorumin F,3 and 441772-64-1
(CAS Registry Number) (Fig. 1).4
hexene ring would be derived from an endo transition state, while
the trans–trans stereochemistry would be obtained from the exo
transition state. The feasibility of such a [4+2] cycloaddition reac-
tion has recently been demonstrated by Porco and co-workers,5,6
Rizzacasa and co-workers,7,8 and our group.9 It was envisaged that
the ortho and para hydroxyl groups on the aryl ring of diene II
could be selectively protected due to their relative positions to
the carbonyl group. Subsequent intramolecular cyclization of the
cis–trans (endo) adducts III and IV would then produce morusal-
banol A and 441772-64-1, respectively.
In continuation of our interest in the syntheses of mulberry
Diels–Alder adducts, we wanted to develop a viable procedure
Results and discussion
for the synthesis of morusalbanol
A
and 441772-64-1.
Nonetheless, an important issue needed to be addressed during
the planning of the synthesis of these compounds: the formation
of the requisite cis–trans (endo) Diels–Alder precursor. Our
approach hinged on the hydrogen bond-assisted regioselective
Diels–Alder reaction between chalcone dienophile I and dehy-
droprenyl diene II (Scheme 1), which would result in the formation
Prior to embarking on the total synthesis of morusalbanol A and
441772-64-1, we examined the [4+2] cycloaddition reaction using
model dienes 1a,b and dienophiles 2a,b (Table 1). We anticipated
that deprotection of the para hydroxyl group would enable cis–
trans (endo) Diels–Alder adduct 3a to undergo intramolecular
cyclization to produce the oxabicyclic [3.3.1] skeleton found in
441772-64-1, while the para methyl ether protected, cis–trans
(endo) Diels–Alder adduct 3b would undergo bond rotation and
⇑
Corresponding author.
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.