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Il Farmaco 54 (1999) 265–274
From ascorbigens to indolocarbazoles
Maria N. Preobrazhenskaya a,*, Alexander M. Korolev a, Ilya I. Rozhkov a,
Larisa N. Yudina a, Eduard I. Lazhko a, Enrico Aiello b, Anna Maria Almerico b,
Francesco Mingoia c
a Institute of New Antibiotics, Russian Academy of Medical Sciences, B. Pirogo6skaya 11, Moscow 119867, Russia
b Uni6ersita` degli Studi, Istituto Farmacochimico 6ia Archirafi 32, 90123 Palermo, Italy
c Istituto di Chimica e Tecnologia dei Prodotti Naturali-CNR, Via Ugo La Malfa 153, 90123 Palermo, Italy
Received 30 December 1998; accepted 1 March 1999
Abstract
New methods of
b-hydroxy-N-methyltryptamine and
2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)-cyclopen-2-enone. Similarly, 4-hydroxy-3-methoxyphenylglycolic and
yielded 2-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-4-hydroxymethyl-cyclopen-2-enone. Properties of N-methoxyascorbigen
(neoascorbigen) were investigated. Alkylation of -ascorbic acid with polysubstituted pyrrolecarbinols led to pyrrole analogues of
L
-ascorbic acid derivatization with the use of polyfunctional indole-3-cabinols are described. Reaction of
-ascorbic acid gave lactame derivatives; (indol-3-yl)glycolic and -ascorbic acids produced
-ascorbic acids
L
L
L
L
ascorbigen. Acidic transformation of 3-formylindole and 1-methyl-3-formylindole led to indolocarbazoles and triindolylmethane
derivatives. © 1999 Elsevier Science S.A. All rights reserved.
Keywords: Ascorbigen; L-Ascorbic acid; 3-Formylindole; Indolocarbazole; Neoascorbigen; Indolecarbinol; Pyrrolecarbinol
The facile 2-C-alkylation of ascorbic acid prompted
L
-Ascorbic acid is easily alkylated in mild conditions
us to study the interaction of polyfunctional indole-3-
carbinols with ascorbic acid. Indole-3-carbinols, with
functional groups in the neighbourhood of carbinol
hydroxyl, interact with ascorbic acid with the participa-
tion of the functional group. Earlier we investigated the
(room temperature, water–alcohol solution, pH 4–5)
with 3-hydroxymethylindole, with the formation of
ascorbigen (2-C-[(indol-3-yl)methyl]-a-L-xylo-3-hexulo-
furanosono-1,4-lactone (Asc), (Scheme 1) [1].
3-Hydroxymethylindole is formed in plants of the
cruciferous family from the alkaloid glucobrassicin, and
interaction of (indol-3-yl)ethandiol-1,2 with
L-ascorbic
acid, which yielded a mixture of products of the
L
-
its interaction with
L-ascorbic acid in plant tissues
ascorbic acid 2-C alkylation with the substituted skatyl
cation stabilized by the 3-CO hemiketal formation with
the participation of the CH2OH moiety of (indol-3-
yl)ethandiol-1,2 [6a,b]. The interaction of DL-N-methyl-
proceeds nonenzymatically [2]. For animals and hu-
mans Asc is a main source of 5H,11H-indolo[3,2-b]-
carbazole (ICZ), a natural potent Ah receptor agonist.
The Ah receptor is a widely occurring ligand-activated
transcription factor that mediates the activation of cy-
tochrome 4501A1, P4501A2, glutathione S-transferase,
and quinone reductase genes. The binding activity of
ICZ is only a factor of 3.7×10−2 lower than that of
the highly toxic environmental contaminant and cancer
promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin [3–5].
b-hydroxytryptamine with
L-ascorbic acid proceeds
through the 2-C alkylation of the latter and the in-
tramolecular acylation of the methylamino group, to
yield diastereomeric 3-hydroxy-4-(indol-3-yl)-1-methyl-
3-(2,3,4-trihydroxybutyryl)-pyrrolid-2-ones (4a and 5b)
(Scheme 2), [7]. The 3-C–6-C moiety of ascorbic acid in
isomer 4a represents a cyclic hemiacetal (1%-C–4%-C),
whereas in isomer 5b it exists as an acyclic trihydroxy-
butyryl residue. Acetylation of compounds 4a and 5b
with acetic anhydride in pyridine at −16°C afforded 6a
and 6b, respectively, whose deacetylation (MeONa in
* Corresponding author. Tel.: +7-095-245-3753; fax: +7-095-245-
0295.
E-mail address: lcta@space.ru (M.N. Preobrazhenskaya)
0014-827X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0014-827X(99)00026-9