A new synthesis of two naturally occurring dihydrobenzo[b]furan-type neolignans of potential biological activity

Article abstract of DOI:10.1515/znb-2001-0612

A new synthesis of the racemates of two naturally occurring neolignans 1 and 2 was achieved via the 2,3-dihydrobenzo[b]furan derivative 3, starting from the commercially available materials o-vanillin (6) and acetovanillone (9). Benzofurans, Neolignan, Heck Reaction.

Full text of DOI:10.1515/znb-2001-0612

A New Synthesis of Two Naturally Occurring Dihydrobenzo[6]furan-Type
Neolignans of Potential Biological Activity
László Juhász3, Z oltán D inya3, Sándor A ntus3, and Tamás E. Gundab
a Department of Organic Chemistry, University of Debrecen, P. O.Box 20,
H-4010 Debrecen, Hungary
b Research Group of Antibiotics of the Hungarian Academy of Sciences,
University of Debrecen, P. O.Box 70, H-4010 Debrecen, Hungary
Reprint requests to Sändor Antus. Fax: +36-52-453-836. E-mail: antuss@tigris.klte.hu
Z. Naturforsch. 56b, 554-559 (2001); received May 31, 2000
Benzofurans, Neolignan, Heck Reaction
A new synthesis of the racemates of two naturally occurring neolignans 1 and 2 was
achieved via the 2,3-dihydrobenzo[£>]furan derivative 3, starting from the commercially avail-
able materials o-vanillin (6) and acetovanillone (9).
Neolignans possessing a 2,3-dihydrobenzo[£>]-
one (2) from Zyziphus jujuba Mill [16] showing
furan skeleton are a class of naturally occurring a significant PG I2 inducing effect. Although our
heterocyclic compounds with hepatoprotective [1],
horm one blocking [2,3], antibacterial [4], antifun-
previous approach [13] based on the oxidative
coupling of methyl ferulate led to these natural
gal [5], plant grow regulator [6], and antioxidant products (1, 2) in a straightforward fashion, it still
[7] activity. The basic ring system of these com- appeared reasonable to examine related new
pounds can be biosynthetically deduced by dimer-
ization of p-propenylphenols, such as isoeugenol,
coniferyl or sinapyl alcohol. Until now the practi-
cal synthetic routes to this structure were based
also on this biomimetic process involving a neutral
phenoxy radical [8,9], or phenoxonium ion [10],
intermediate. We previously published also a pre-
liminary communication on a new approach for
the synthesis of dihydrobenzo[£]furan-type neolig-
methods permitting the synthesis of their ana-
logues differing in the side-chain at C-5.
The strategy of our synthesis was based on the
well-documented synthetic availability of racemic
3 from the commercially available starting m ateri-
als o-vanillin (6) and acetovanillone (9) [17]. Thus,
according to our assumption based on quant-
umchemical calculation brom ination of the acetyl
derivative 4 took place at C-5 with high selectivity
to result in the 5-bromo-2,3-dihydrobenzo[Z>]furan
derivative 5 in high yield (80% ) [11]. Beside the
'H NM R evidences its structure was indepently
proved by its synthesis from o-vanillin (6) as il-
lustrated in Scheme 2. In the first step 6 was re-
acted with bromine in acetic acid at 0° C to give 7
nans via 2,3-dihydrobenzo[fr]furan derivative
3
[Hl-
In this paper as a continuation of our investiga-
tions of biologically active natural neolignans [11-
14] we report a full account of this approach using
for the synthesis of two naturally occurring dihy-
drobenzo[fr]furan-type neolignans. The first com- in good yield (80%). Its TH NM R spectrum clearly
pound, (-)-balanophonin (1), was isolated from
showed that bromination of the benzene nucleus
Balanophora japonica Mikino [15] and the second
of 6 took place at the
para position to the hydroxyl
R1
R2
H
H
ivA 4-.OR
OMe
^
'
1
2
-(E) -CH=CH-CHO
-(£)-CH=CH-C02CH3
1 H
H
Ac
Ac
3
4
5
H
2 i-'x r3" ° Me
H
Br
-OR
Scheme 1.
0932-0776/2001/0600-0554 $06.00 © 2001 Verlag der Zeitschrift für Naturforschung, Tübingen • www.znaturforsch.com
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