Elaboration of the isochromane system of stephaoxocanes employing an Oxa-Pictet Spengler type cyclization

Article abstract of DOI:10.3390/50300493

An approach to the synthesis of the isochromane moiety embodying the AC-ring system of the stephaoxocanes, by the use of an Oxa-Pictet Spengler type cyclization strategy, is reported.

Full text of DOI:10.3390/50300493

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93
Molecules 2000, 5
Elaboration of the Isochromane System of Stephaoxocanes
Employing an Oxa-Pictet Spengler Type Cyclization
1
2
1
2
Teodoro S. Kaufman , Carmem R. Bernardi , Marcos Cipulli and Claudio C. Silveira
1
Instituto de Química Orgánica de Síntesis -IQUIOS-(CONICET-UNR) and Facultad de Ciencias Bio-
químicas y Farmacéuticas, Universidad Nacional de Rosario, P.O.B. 991, 2000 Rosario, Argentina
2
Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil
E-mail: tkaufman@agatha.unr.edu.ar
Abstract: An approach to the synthesis of the isochromane moiety embodying the AC-ring
system of the stephaoxocanes, by the use of an Oxa-Pictet Spengler type cyclization strat-
egy, is reported.
Stephania excentrica and Stephania cepharantha (Menispermaceae) are herbs employed since an-
cient times in traditional Chinese medicine. They are the source of many interesting natural products,
among them the stephaoxocanes, a small family of tetracyclic isoquinoline alkaloids with only a few
known members [1].
R1
MeO
MeO
N
N
H
H
N
R1
MeO
R
MeO
H
O
O
OH
O
R2
OH
OH
R = MeO, R = OH
1
2
Stephaoxocanidine (1)
R = R = H, Stephaoxocane
R= H Excentricine
R= Me 2-N-Methylexcentricine
1
2
Stephaoxocanine
The interesting structural characteristics of these natural products in relationship with our research
work [2] prompted us to study the elaboration of models for the total synthesis of natural stephaoxo-
canes, particularly stephaoxocanidine (1).
In this communication, we report the elaboration of isochromanone 2 starting from commercially
available m-anisaldehyde (3), following an Oxa-Pictet-Spengler type strategy [3].
As shown in the Scheme, bromination of 3 with bromine in AcOH provided bromoaldehyde 4,
which olefination under Wittig conditions gave olefins 5. Next, dihydroxylation of the double bond
followed by transacetalization of the resulting diol with acetal furnished acetal 7, which TiCl pro-
4

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Molecules 2000, 5
moted cyclization [4] yielded isochromanol 8. Finally, Swern oxidation of 8 allowed the obtention of
ketone 2.
Br
Br
Br
Wittig
Dihydroxylation
OH
OH
MeO
CHO
MeO
MeO
3
4
R= H
R= Br
5
6
Transacetalization
Br
Br
Br
Swern
Oxa-PS
O
H
OH
H
O
O
MeO
MeO
MeO
H
H
O
O
2
8
7
Only one diastereoisomer is shown
The Wittig reaction resulted in a mixture of olefins the isomerization of which was not studied in
this preliminary approach; therefore, products 6-8 as well as 2 were obtained as diastereomeric mix-
tures, keeping the product the proportion found in the starting material.
Details of the synthesis, the cyclization reaction course with different model molecules and syn-
thetic potential of this strategy will be discussed.
Acknowledgements: To Fundación Antorchas, CONICET, SECyT-UNR, AUGM and ANPCyT for
grants received.
References and Notes
1
.
.
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Rep. 1997, 9, 177; (b) Deng, J.-Z.; Zhao, S.-X.; Miao, Z.-C. Nat. Prod. Lett. 1993, 2, 283.
(a) Kaufman, T. S. J. Chem. Soc., Perkin Trans. 1 1993, 403; (b) Kaufman, T. S. J. Chem. Soc.,
Perkin Trans. 1 1996, 2497; (c) Ponzo, V. L.; Kaufman, T. S. J. Chem. Soc., Perkin Trans. 1
2
1
997, 3131.
3
4
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Wünsch, B.; Zott, M. Liebigs Ann. Chem. 1992, 39.
Giles, R. G. F.; Rickards, R. W.; Senanayake, B. S. J. Chem. Soc., Perkin Trans. 1 1996, 2241.